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  • 1. Agmon-Levin, Nancy
    et al.
    Damoiseaux, Jan
    Kallenberg, Cees
    Sack, Ulrich
    Witte, Torsten
    Herold, Manfred
    Bossuyt, Xavier
    Musset, Lucille
    Cervera, Ricard
    Plaza-Lopez, Aresio
    Dias, Carlos
    Sousa, Maria Jose
    Radice, Antonella
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Hultgren, Olof
    Viander, Markku
    Khamashta, Munther
    Regenass, Stephan
    Coelho Andrade, Luis Eduardo
    Wiik, Allan
    Tincani, Angela
    Ronnelid, Johan
    Bloch, Donald B.
    Fritzler, Marvin J.
    Chan, Edward K. L.
    Garcia-De la Torre, I.
    Konstantinov, Konstantin N.
    Lahita, Robert
    Wilson, Merlin
    Vainio, Olli
    Fabien, Nicole
    Sinico, Renato Alberto
    Meroni, Pierluigi
    Shoenfeld, Yehuda
    International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, nr 1, s. 17-23Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.

  • 2.
    Berglin, Ewa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Mohammad, Aladdin J.
    Department of Clinical Sciences/Rheumatology, Lund University, Lund, Sweden; Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
    Dahlqvist, Johanna
    Department of Medical Biochemistry and Microbiology, and Medical Sciences, Uppsala University, Uppsala, Sweden.
    Johansson, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Sjöwall, Johanna
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Clinic of Infectious Diseases Linköping University Hospital, Linköping, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis: a case-control study2021Ingår i: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 117, artikel-id 102579Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed.

    Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities.

    Results: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p < 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3–7.7) years and MPO-ANCA+ 2.0 (0.9–3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P < 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p < 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p < 0.01 and p < 0.05, respectively).

    Conclusion: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.

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  • 3.
    Bodecker-Zingmark, L.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Widbom, Lovisa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Anti-Saccharomyces Cerevisiae antibodies are only modestly more common in subjects later developing Crohn's disease2023Ingår i: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 68, s. 608-615Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The pathogenic processes in the preclinical phase of inflammatory bowel disease (IBD) are mainly unknown.

    Aims: To study typical antibodies for IBD in the preclinical phase in a cohort of Northern Sweden.

    Methods: Antibodies typical for IBD (ASCA, pANCA, lactoferrin-ANCA, antibodies to goblet cells, and pancreas antigen) were analyzed in 123 subjects with preclinical ulcerative colitis (UC), 54 subjects with preclinical Crohn's disease (CD) and in 390 sex- and age-matched controls. In addition, in a subset of subjects, inflammatory markers (CRP, albumin, calprotectin and ferritin) were measured in plasma.

    Results: The mean years between blood samples and IBD diagnosis were for UC 5.1 (SD 3.5) years and CD 5.6 (SD 3.5) years. There was no difference in the proportion of overall positive antibodies between subjects who later developed IBD compared to controls (16.9% vs. 12.3%; p = 0.137). The subjects who later developed CD had a significantly higher proportion of positive ASCA compared to controls (9.3% vs 2.8%; p = 0.034), but for all other antibodies, there were no differences compared to control subjects. Subjects with preclinical IBD and elevated antibodies showed significantly higher plasma calprotectin levels compared to subjects without antibodies (980 μg/L vs 756 μg/L; p = 0.042), but there was no difference in the levels of CRP, albumin and ferritin.

    Conclusions: We found no significant increase in antibodies typical for IBD years before diagnosis except for ASCA, which was slightly more common in subjects who later developed CD. Very few subjects had detectable antibodies to goblet cells and pancreas antigen.

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  • 4.
    Bonroy, Carolien
    et al.
    Department of Diagnostic Sciences, Ghent University, Ghent, Belgium; Department of Laboratory Medicine, University Hospital Ghent, Ghent, Belgium.
    Vercammen, Martine
    Department of Laboratory Medicine, AZ Sint-Jan, Brugge, Belgium; Research Group REIM, Vrije Universiteit Brussel, Brussels, Belgium.
    Fierz, Walter
    Schweizerischer Verband der Diagnostikindustrie (SVDI-ASID), Bern, Switzerland.
    Andrade, Luis E.C.
    Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Immunology Division, Fleury Medicine and Health Laboratories, Sao Paulo, Brazil.
    Van Hoovels, Lieve
    Department of Laboratory Medicine, OLV Hospital, Aalst, Belgium; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
    Infantino, Maria
    Immunology and Allergology Laboratory, S. Giovanni di Dio Hospital, Florence, Italy.
    Fritzler, Marvin J.
    Department of Medicine, Cumming School of Medicine, University of Calgary, AB, Calgary, Canada.
    Bogdanos, Dimitrios
    Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, University General Hospital of Larissa, Larissa, Greece.
    Kozmar, Ana
    Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia.
    Nespola, Benoit
    Laboratory of Immunology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
    Broeders, Sylvia
    Quality of Laboratories, Sciensano, Ixelles, Belgium.
    Patel, Dina
    UK NEQAS Immunology, Immunochemistry and Allergy, Sheffield Teaching Hospitals, Sheffield, United Kingdom.
    Herold, Manfred
    Department of Internal Medicine II, Rheumatology Laboratory, Medical University of Innsbruck, Innsbruck, Austria.
    Zheng, Bing
    Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
    Chan, Eric Y.T.
    Department of Pathology, Queen Mary Hospital, Hong Kong, Hong Kong.
    Uibo, Raivo
    Department of Immunology, Medical Faculty, University of Tartu, Tartu, Estonia.
    Haapala, Anna-Maija
    Department of Immunology, Fimlab Laboratories, Tampere, Finland.
    Musset, Lucile
    Department of Immunology, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
    Sack, Ulrich
    Medical Faculty, Leipzig University, Leipzig, Germany.
    Nagy, Gabor
    Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
    Sundic, Tatjana
    Department of Immunology and Transfusion Medicine, Haugesund Hospital, Helse Fonna, Haugesund, Norway.
    Fischer, Katarzyna
    Individual Laboratory for Rheumatologic Diagnostics, Pomeranian Medical University in Szczecin, Szczecin, Poland.
    Rego De Sousa, Maria-José
    Immunopathology and Autoimmunity Department, Centro de Medicina Laboratorial Germano de Sousa, Lisbon, Portugal.
    Vargas, Maria Luisa
    Immunology, Hospital Universitario de Badajoz, Badajoz, Spain.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Heijnen, Ingmar
    Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
    García-De La Torre, Ignacio
    Department of Immunology and Rheumatology, Hospital General de Occidente, Universidad de Guadalajara, Guadalajara, Mexico.
    Carballo, Orlando Gabriel
    Laboratory of Immunology, Hospital Carlos G. Durand, Buenos Aires, Argentina; Department of Microbiology and Immunology, Instituto Universitario, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
    Satoh, Minoru
    Department of Human, Information and Life Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Medicine, Kitakyushu Yahata-Higashi Hospital, Kitakyushu, Japan.
    Kim, Kyeong-Hee
    Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, South Korea.
    Chan, Edward K.L.
    Department of Oral Biology, University of Florida, FL, Gainesville, United States.
    Damoiseaux, Jan
    Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, Netherlands.
    Lopez-Hoyos, Marcos
    Immunology Service, University Hospital Marques de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain.
    Bossuyt, Xavier
    Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; Department of Laboratory Medicine, University Hospital Leuven, Leuven, Belgium.
    The European Autoimmune Standardization Initiative (EASI), (Medarbetare/bidragsgivare)
    The International Consensus on ANA Patterns (ICAP), (Medarbetare/bidragsgivare)
    Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP2023Ingår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 61, nr 7, s. 1167-1198Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA).

    Methods: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group “Autoimmunity Testing”; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP).

    Results: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations.

    Conclusions: These recommendations are an important step to achieve high quality ANA testing.

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  • 5. Damoiseaux, J.
    et al.
    Agmon-Levin, N.
    Van Blerk, M.
    Chopyak, V.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Heijnen, I.
    Herold, M.
    Hogasen, K.
    Musset, L.
    Radice, A.
    Rego de Sousa, M. J.
    Viander, M.
    Shoenfeld, Y.
    From ANA-screening to antigen-specificity: an EASI-survey on the daily practice in European countries2014Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 32, nr 4, s. 539-546Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    One of the main goals of the European Autoimmunity Standardisation Initiative (EASI) is the harmonisation of test-algorithms for autoantibodies related to systemic autoimmune rheumatic diseases (SARD).

    Methods

    A questionnaire was used to gather information on methodology, interpretation, and the algorithm for detection of anti-nuclear antibodies (ANA) in relation to their antigen-specificity. The questionnaire was sent to 1200 laboratories in 12 European countries.

    Results

    The response rate was 47.2%. The results reveal not only apparent differences between countries, but also within countries.

    Conclusion

    Awareness of these differences may as such already stimulate harmonisation, but the observed differences may also direct recommendations that may further contribute to achieving the EASI goal of harmonisation of autoimmune diagnostics for SARD.

  • 6. Damoiseaux, Jan
    et al.
    Heijnen, Ingmar
    Van Campenhout, Christel
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Fabien, Nicole
    Herold, Manfred
    van der Molen, Renate G.
    Egner, William
    Patel, Dina
    Plaza-Lopez, Aresio
    Radice, Antonella
    Rego de Sousa, Marie Jose
    Viander, Markku
    Shoenfeld, Yehuda
    An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice2018Ingår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 56, nr 10, s. 1759-1770Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Detection of anti-neutrophil cytoplasmic antibodies (ANCA) is important for the diagnosis of the ANCA-associated vasculitides (AAV). For AAV, especially ANCA directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are most relevant. ANCA with less well-defined specificities may, however, also be detected in other inflammatory and non-inflammatory conditions.

    Methods: A questionnaire, initiated by the European Autoimmunity Standardisation Initiative (EASI), was used to gather information on methods and testing algorithms used for ANCA in clinical laboratories of 12 European countries (EASI survey).

    Results: Four hundred and twenty-nine responses were included in the EASI survey analysis which revealed differences within countries and between countries. Laboratories overall were poor in adherence to international consensus on ANCA testing. Substantial variation was observed with respect to the use of ANCA indirect immunofluorescence (IIF) in the algorithm, application of distinct methods for MPO- and PR3-ANCA, the daily availability of new ANCA results, and interpretation of test results.

    Conclusions: Awareness of these differences may stimulate further harmonization and standardization of ANCA testing. This may be promoted by an update of the international ANCA consensus and the introduction of international standards.

  • 7.
    Dragon-Durey, Marie-Agnès
    et al.
    Laboratoire d'Immunologie, Hôpital Européen Georges Pompidou, APHP, Université de Paris Cité, Paris, France.
    Bizzaro, Nicola
    Laboratory of Clinical Pathology, San Antonio Hospital, Azienda Sanitaria Universitaria Integrata, Udine, Italy.
    Senant, Marie
    Cerballiance, Lisses, France.
    Andreeva, Hristina
    Section of Protein Allergy and Immunology, Laboratory Medicine Department, Diagnostic Clinic, University Hospital of North Norway, Tromsø, Norway.
    Bogdanos, Dimitrios P.
    Department of Rheumatology and Clinical Immunology, Fac. of Med., Sch. of Hlth. Sciences, University of Thessaly, University General Hospital of Larissa, Larissa, Greece.
    Bonroy, Carolien
    Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
    Bossuyt, Xavier
    Department of Microbiology, Immunology and Transplantation, Ku Leuven, Belgium.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Fabien, Nicole
    Immunology Department, Hospices Civils de Lyon, Pierre-Bénite, France.
    Heijnen, Ingmar
    Medical Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
    Herold, Manfred
    Rheumatology Laboratory, Department of Internal Medicine Ii, Medical University of Innsbruck, Innsbruck, Austria.
    Musset, Lucile
    Département d'Immunologie, Uf Immunochimie and Autoimmunité, Chu Pitié Salpêtrière-Ch Foix, Aphp, Paris, France.
    Kuhi, Liisa
    Central Laboratory, Diagnostic Clinic, East Tallinn Central Hospital, Tallinn, Estonia.
    Lopez-Hoyos, Marcos
    Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain.
    Berki, Tímea
    Department of Immunology and Biotechnology, University of Pécs, Medical School, Pécs, Hungary.
    Roozendaal, Caroline
    Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
    Sack, Ulrich
    Medical Faculty, Institute of Clinical Immunology, University Leipzig, Leipzig, Germany.
    Sundic, Tatjana
    Immunology and Transfusion Medicine, Department of Laboratory Medicine, Haugesund Hospital, Haugesund, Norway.
    Taylor, Lorna
    Department of Immunology, Black Country Pathology Services, Wolverhampton, West Midlands, United Kingdom.
    Kuna, Andrea Tesija
    Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.
    Damoiseaux, Jan
    Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, Netherlands.
    Repository of intra-and inter-run variations of quantitative autoantibody assays: A European multicenter study2022Ingår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 60, nr 9, s. 1373-1383Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    No reference data are available on repositories to measure precision of autoantibody assays. The scope of this study was to document inter-and intra-run variations of quantitative autoantibody assays based on a real-world large international data set. Members of the European Autoimmunity Standardisation Initiative (EASI) group collected the data of intra-and inter-run variability obtained with assays quantifying 15 different autoantibodies in voluntary participating laboratories from their country. We analyzed the impact on the assay performances of the type of immunoassay, the number of measurements used to calculate the coefficient of variation (CVs), the nature and the autoantibody level of the internal quality control (IQC). Data were obtained from 64 laboratories from 15 European countries between February and October 2021. We analyzed 686 and 1,331 values of intra-and inter-run CVs, respectively. Both CVs were significantly dependent on: The method of immunoassay, the level of IQC with higher imprecision observed when the antibody levels were lower than 2-fold the threshold for positivity, and the nature of the IQC with commercial IQCs having lower CVs than patients-derived IQCs. Our analyses also show that the type of autoantibody has low impact on the assay' performances and that 15 measurements are sufficient to establish reliable intra-and inter-run variations. This study provides for the first time an international repository yielding values of intra-and inter-run variation for quantitative autoantibody assays. These data could be useful for ISO 15189 accreditation requirements and will allow clinical diagnostic laboratories to assure quality of patient results.

  • 8.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Immunological mechanisms in systemic autoimmunity: autoantibodies and chemokines in systemic lupus erythematosus and during treatment with TNF inhibitors in rheumatoid arthritis2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background. Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that, without powerful treatment, may lead to irreversible joint damage. During the past decade, anti-cytokine therapy has become available, e.g., infliximab, a chimeric antibody targeting the pro-inflammatory cytokine TNF that has a central role in the inflammatory process in RA patients. Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that may affect all organs and is characterized by a massive antibody production. Chemokines, chemokine receptors and lipoprotein receptor-related protein 1(CD91) are regulators of inflammation in autoimmune diseases and T-cell migration.

    Objectives. The aim of this study was to get a deeper understanding how TNF blocking treatment influences inflammatory mechanisms and autoantibody formation in RA with special reference to similarities and differences with SLE.

    Methods. In patients with RA treated with anti-TNF, and in SLE patients (ACR criteria) clinical evaluation was performed and blood samples analyzed. Autoantibodies were analyzed using indirect immunofluorescence, ELISA and multiplex flow cytometry in samples from anti-TNF treated RA patients (n=59) followed longitudinally for 54 weeks, in pre-diseased samples from SLE patients (n=38) and matched population-based controls (n=152). T-cell expression of chemokine receptors and CD91 was analyzed by flow cytometry, whilst serum levels of chemokines were determined using ELISA in anti-TNF treated RA-patients (n=24) followed longitudinally (30 weeks), and cross-sectionally in SLE-patients (n=23). Expression of mRNA for chemokines was analyzed in T-cells from SLE-patients (n=10) using PCR.

    Results. After treatment with infliximab, RA patients produced ANA, anti-dsDNA and anti-nucleosome antibodies, but not anti-ENA antibodies. Although these antibodies are considered typical for SLE only one patient developed a transient lupus-syndrome. Antibodies against cell nuclear antigens, including ENA, were detected several years before the first clinical symptom of SLE; anti-SSA was the earliest detectable antibody.

    In RA-patients before infliximab treatment, the T-cell expression of several chemokine receptors was elevated compared with healthy controls. In contrast, only one soluble chemokine, IP-10 was elevated. After treatment the levels of soluble MIP-1β, MCP-1 and IP-10, and the T-cell expression of CCR2 were decreased. In SLE-patients MIP-1β, MCP-1, SDF-1, IP-10 and RANTES in blood were elevated, whilst expression of CXCR5 and CCR6 on T-cells was lower than in healthy controls. T-cell expression of CXCR2 and CCR1 was elevated in active disease (measured as SLEDAI index), whereas the CXCR5 and CCR2 expression was lower in inactive SLE. In SLE patients with nephritis IP-10 was lower and T-cell expression of CXCR3 and CCR3 elevated compared with patients without nephritis. The expression of CD91 was higher on T-cells from patients not responsive to infliximab treatment compared with responders.

    Conclusion. These findings indicate that anti-TNF (infliximab) treatment in RA-patients has a major impact on the production of autoantibodies and chemokines. The autoantibody profile in infliximab-treated patients was similar to that predating disease onset in SLE patients with the exception of anti-ENA being detectable in SLE, but the development of lupus-syndromes was rare. The expression of CD91 on T-cells may predict responsiveness to infliximab. The expression of chemokine receptors in SLE- patients seemed to be related to disease activity. Anti-nuclear antibodies were detectable years before clinical disease onset in patients who developed SLE suggesting a gradual pathogenic process.

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  • 9.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Dahlqvist, Solbritt Rantapää
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Cytokines and Their Relation to Autoantibodies Before Disease Onset in Systemic Lupus Erythematosus2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr 10, s. S286-S287Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Eneslätt, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Ivanoff, J
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, Karl-Gösta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus2003Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 12, nr 10, s. 766-774Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The expression of chemokine receptors on T-cells and chemokine levels in the blood was studied in 23 patients with SLE (ACR criteria), seven patients with rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002, respectively). The decrease of CXCR5 was confined to SLE patients with inactive disease (SLEDAI < 6) compared with active disease (SLEDAI &GE; 6) and controls. CXCR2 and CCR1 were increased in patients with active SLE compared with patients with inactive disease (P = 0.001 and P = 0.01, respectively) and with controls ( P = 0.02 and P = 0.053, respectively). The levels of the chemokines MIP-1β MCP-1, SDF-1α, IP-10 and RANTES were significantly elevated in SLE patients compared with controls. Patients with renal involvement had increased surface expression of CXCR3 and CCR3 (P = 0.04 in both) and a lower level of soluble IP-10 compared with patients without renal disease (P = 0.025) and compared with controls (P = 0.001). The ratio between CCR5 and CCR3 was significantly increased in RA patients compared with SLE patients and controls supporting a Th1 overweight in RA. In conclusion, patients with SLE showed abnormal T-cell expression of several chemokine receptors and levels of soluble chemokines in their plasma/ serum.

  • 11.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Engstrand, S
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, K-G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha2005Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, nr 3, s. 403-407Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Research on autoantibody formation in patients treated with TNFα inhibitors has produced contradictory results.

    Objective: To study the prevalence of autoantibodies in patients with rheumatoid arthritis treated with the TNFα inhibitor infliximab.

    Methods: 53 patients (48 female, 11 male) treated with infliximab for rheumatoid arthritis were followed for autoantibody production before treatment and after 14, 30, and 54 weeks. Six patients treated with etanercept were studied for comparison. The analyses included antibodies against nuclear antigens (ANA), extractable nuclear antigens, double stranded (ds)DNA (by ELISA, IIF on Crithidia luciliae for IgM and IgG, and Farr assay), nucleosomes, cardiolipin, smooth muscle, mitochondria, proteinase 3, and myeloperoxidase antigens.

    Results: The number of patients treated with infliximab who developed antibodies against dsDNA of both IgG and IgM class (tested by IIF) increased significantly. The prevalence of patients positive for IgG class increased to 66% at 30 weeks and 45% at 54 weeks, and of IgM class to 85% and 70%, respectively. The titre and number of patients expressing antibodies against nucleosomes and ANA also increased significantly. The number of rheumatoid factor or anticardiolipin positive patients was stable and there was no increase in antibodies against the other antigens. A lupus-like syndrome was seen in one patient. No patient treated with etanercept developed any of these autoantibodies.

    Conclusions: Patients treated with infliximab may develop anti-dsDNA antibodies of both IgM and IgG class, anti-nucleosome antibodies, and ANA, with a gradual increase until 30 weeks.

  • 12.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Johansson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Autoantibodies predate the onset of Systemic Lupus Erythematosus in northern Sweden2011Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, nr 1, s. R30-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Autoantibodies have a central role in systemic lupus erythematosus (SLE). The presence of autoantibodies preceding disease onset by years has been reported both in patients with SLE and those with rheumatoid arthritis, suggesting a gradual development of these diseases. To identify autoantibodies in a Northern European population predating the onset of symptoms of SLE and their relationship to presenting symptoms.

    METHODS: The register of patients fulfilling the American College of Rheumatology (ACR) criteria for SLE and with a given date for the onset of symptoms was co-analysed with the register of the Medical Biobank, Umea, Sweden. Thirty-eight patients were identified as having donated blood samples prior to symptom onset. A nested case-control study (1:4) was performed with 152 age- and sex-matched controls identified from within the Biobank register. Antibodies against anti- Sjogren's syndrome antigen A (Ro/SSA) (60 and 52 kDa), anti- Sjogren's syndrome antigen B (La/SSB), anti-Smith antibody (Sm), ribonucleoprotein (RNP), scleroderma-70 (Scl-70), anti- histidyl-tRNA synthetase antibody (Jo-1), double-stranded DNA (dsDNA); Centromere protein B and histones were analysed using the anti-nuclear antibody test II (ANA-II) Plus Test System (Athena Multi-Lyte(R)) on a Bio-Plex Array Reader (Luminex200). ANA were analysed using indirect immunofluorescence on Human Epidermal cells-2 (HEp2-cells) at a sample dilution of 1:100.

    RESULTS: Autoantibodies against nuclear antigens were detected 5.6 (+/- 4.7; mean +/- SD) years before the onset of symptoms and 8.7 (+/- 5.6) years before diagnosis in 63% of the individuals who subsequently developed SLE. The sensitivity (45.7%) was highest for ANA with a specificity of 95%, followed by anti-dsDNA and anti-Ro/SSA antibodies both with sensitivities of 20.0% at specificities of 98.7% and 97.4%, respectively. The odds ratio (OR) for anti-dsDNA predicting disease was 18.13 (CI 95%; 3.58-91.84), and for ANA 11.5 (CI 95%; 4.54-28.87). Anti-Ro/SSA antibodies appeared first, 6.6 (+/- 2.5) years prior to symptom onset. The mean number of autoantibodies in pre-diseased individuals was 1.4 and after disease onset 3.1 (P< 0.0005). The time predating disease was shorter, and the number of autoantibodies greater, in those individuals with serositis as a presenting symptom in comparison to those with arthritis and skin manifestations.

    CONCLUSIONS: Autoantibodies against nuclear antigens were detected in individuals developing SLE several years before the onset of symptoms and diagnosis. The most sensitive autoantibodies were ANA, Ro/SSA and dsDNA, with the highest predictive OR for anti-dsDNA antibodies. The first autoantibodies detected were anti-Ro/SSA.

  • 13.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Cytokines in relation to autoantibodies before onset of symptoms for systemic lupus erythematosus2014Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 23, nr 7, s. 691-696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: A number of cytokines and chemokines were analysed and related to autoantibodies in blood samples pre-dating the onset of symptoms of systemic lupus erythematosus. Methods: Thirty-five patients with systemic lupus erythematosus (American College of Rheumatology criteria) were identified as having donated blood samples, prior to symptom onset, to the Biobank of northern Sweden. Altogether, 140 age-and sex-matched controls were also identified. The concentrations of interferon-a, interleukin-4, interleukin-9, interleukin-10, interferon inducible protein-10 and monocyte chemotactic protein-1 were analysed using multiplex technology and related to autoantibodies (ANA, ENA, anti-dsDNA and anti-histone antibodies) analysed from the same blood sample. Results: The interferon-g inducible protein-10 levels were higher in the pre-symptomatic individuals than in controls (p < 0.05) and correlated with interferon-a (p < 0.01). The interferon-g inducible protein-10 and interferon-a concentrations were significantly increased in individuals positive for autoantibodies: interferon-g inducible protein-10 for ANA; anti-SSA/Ro and anti-Jo-1 antibodies; interferon-a with anti-SSB/La antibodies. The levels of interleukin-10, interferon-g inducible protein-10 and monocyte chemotactic protein-1 increased significantly from the pre-symptomatic individuals to after onset of systemic lupus erythematosus. Conclusions: An increased concentration of interferon-gamma inducible protein-10 pre-dated the onset of systemic lupus erythematosus and was related to autoantibodies before the onset of disease. The levels of interferon-gamma inducible protein-10 and interferon-alpha were correlated. These findings support the proposal that the interferon system is important early in the pathogenesis of systemic lupus erythematosus and autoantibody formation.

  • 14.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, Karl-Gösta
    Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska Institute at Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    T-cell expression of CD91: a marker of unresponsiveness to anti-TNF therapy in rheumatoid arthritis2010Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 118, nr 11, s. 837-845Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate the expression of thrombospondin-1 (TSP-1) and its receptors, lipoprotein receptor-related protein/cluster of differentiation (CD)91, calreticulin (CRT), and CD47, on T cells and monocytes from patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) therapy. The surface expression of CD91 and associated components on CD3- and CD14-positive cells was examined using flow cytometry in 12 patients with established RA before and after beginning therapy and compared with that of 9 healthy controls and 12 patients with early RA treated with conventional therapies. CD3-positive cells from anti-TNF non-responders showed significantly greater expression of CD91 expression than those from responders (p<0.05) after 6 weeks and when all measurements were pooled (p<0.001). CD91 expression on CD3-positive cells from non-responders to other therapies was at the same level as in healthy controls. In contrast, CD14-positive cells showed no differences in CD91 expression between patients and controls or between responders and non-responders to anti-TNF therapy. The expression of TSP-1, CRT, and CD47 showed no differences between responders and non-responders. The results suggest T-lymphocyte expression of CD91 to be a biomarker that signifies unresponsiveness to anti-TNF therapy in patients with RA and may be used to identify potential responders and non-responders.

  • 15.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, KG
    Changes in chemokines and their receptors in blood during treatment with the TNF inhibitor infliximab in patients with rheumatoid arthritis2013Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, nr 4, s. 260-265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Chemokines are involved in leucocyte recruitment into inflammatory sites, such as the synovial tissue of patients with rheumatoid arthritis (RA). The release of certain chemokines is augmented by pro-inflammatory cytokines, such as tumor necrosis factor (TNF). Infliximab, a monoclonal antibody against TNF that blocks the biological effects of TNF, is used in the treatment of chronic inflammatory diseases. The effect of blocking TNF activity on chemokines is not fully understood.

    Aim. The aim of this study was to analyse the effects on chemokines and their receptors on peripheral mononuclear cells of anti-TNF treatment in RA-patients.

    Material and methods. Twelve patients with established RA who began treatment with infliximab, and nine patients with early RA treated with traditional disease-modifying anti-rheumatic drugs, were followed clinically for 30 weeks and chemokine levels in blood samples and chemokine receptor expression on the surface of T-cells and monocytes analysed. Three SLE-patients, as a small control group of another inflammatory disease, and nine healthy subjects were also included in the study.

    Result. CXCL10/IP-10 was significantly higher in RA-patients compared with healthy controls and decreased significantly two weeks after infliximab infusion. CCL2/MCP-1 and CCL4/MIP-1β decreased significantly after infliximab treatment although the concentrations were not significantly elevated at baseline compared with controls. There was an inverse correlation between the chemokine cleaving molecule dipeptidyl peptidase-IV/CD26 and CCL5/RANTES. Several chemokine receptors on T-cells were elevated in RA patients at inclusion into the study. The CCR2 expression on T-cells decreased significantly after infliximab treatment.

    Conclusion. The chemokines CXCL10/IP-10, CCL2/MCP-1 and CCL4/MIP-1β, mainly targeting the Th1 immune response, decreased after treatment with anti-TNF suggesting a more pronounced effect onTh1 activity than on the Th2 mediated response. Several chemokine receptors on blood T-cells were elevated in RA-patients, suggesting that they may be involved in the recruitment of T-lymphocytes from the blood to affected tissues.

  • 16. Erlandsson, Malin C.
    et al.
    Turkkila, Minna
    Siljehult, Filip
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Pullerits, Rille
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Laboratory of Clinical Immunology University Hospital of Umeå , Umeå, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Bokarewa, Maria I.
    Survivin improves the early recognition of rheumatoid arthritis among patients with arthralgia: A population-based study within two university cities of Sweden2018Ingår i: Seminars in Arthritis & Rheumatism, ISSN 0049-0172, E-ISSN 1532-866X, Vol. 47, nr 6, s. 778-785Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Objectives: The aim of this study was to validate the use of survivin for preclinical recognition of rheumatoid arthritis (RA) among patients with unexplained arthralgia.

    Methods: Serum levels of survivin and the arthritis-specific autoantibodies RF and ACPA were measured in total of 5046 patients with musculoskeletal complains during 12 consecutive months in Gothenburg and in Umea. Among them, 303 arthralgia patients were identified and prospectively followed.

    Results: After 48 months, 12.2% of the arthralgia patients developed RA. Most of RA cases had high serum survivin, which increased the relative risk for RA (RR = 5.90,p = 3 x 10(-7)). Combination of survivin with autoantibodies was present in only 4.6% of the arthralgia patients and increased further the risk of RA and shortened time to RA development. Presence of any single autoantibody in the survivin-negative patients was associated with a minor risk for RA and had RA-free survival similar to the reference group.

    Conclusion: This study shows that measurement of survivin in serum improves estimation of RA risk and prospectively predicts RA development in patients with arthralgia. Survivin may indicate a phase preceding autoantibody production. 

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  • 17.
    Hansson, Claes
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Alenius, Gerd-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    S-Calprotectin (S100A8/S100A9): A Potential Marker of Inflammation in Patients with Psoriatic Arthritis2014Ingår i: Clinical & Developmental Immunology, ISSN 1740-2522, E-ISSN 1740-2530, s. 696415-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To analyse levels of S100A8/S100A9 (calprotectin) and selected cytokines, in blood, in patients with psoriatic arthritis (PsA). Methods. Sixty-five patients with PsA were examined for clinical manifestations and laboratory measurements of S-calprotectin, ESR, hs-CRP, and selected cytokines. Thirty-two patients had mono-/oligoarthritis and 33 had polyarthritis. S-calprotectin, hs-CRP, and cytokines were measured using ELISA, immunoturbidimetry, and multiplex technology (Bio-Plex). Patients with PsA were compared with 31 healthy controls. Results. S-calprotectin and hs-CRP levels were significantly higher in patients with PsA compared with controls (P < 0.001 and P < 0.001, resp.). Patients suffering a polyarthritic disease pattern presented with significantly higher levels of S-calprotectin compared with controls and patients with mono-/oligoarthritis (P < 0.001 and P = 0.017, resp.). The levels of S-calprotectin correlated with hs-CRP (P < 0.001; r(s) = 0.441), swollen joint count (P = 0.002, r(s) = 0.397), and CXCL10 (P = 0.046, r(s) = 0.678) but not with any of the other cytokines evaluated. In multiple logistic regression analysis, S-calprotectin was the only variable significantly associated with psoriatic arthritis (P = 0.002, OR = 1.006, 95% CI = 1.002-1.010). Conclusion. S-calprotectin and hs-CRP levels were significantly higher in patients with PsA. A polyarthritic disease pattern showed higher levels of S-calprotectin thanmono-/oligoarthritis. S-calprotectin is considered a potential marker of disease activity in patients with PsA.

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  • 18.
    Innala, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Jidell, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Berglin, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides2008Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 35, nr 6, s. 1002-1008Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA).

    METHODS: The ACPA, e.g., antibodies against mutated citrullinated vimentin (MCV), cyclic citrullinated peptides (CCP) type 2 and 3 (both of IgG isotype) and 3.1 (of both IgG and IgA isotypes), were analyzed at baseline in patients with early RA (n = 210) and in population controls (n = 102) using an enzyme immunoassay. A receiver-operating characteristic curve was constructed for each antibody. Disease activity [swollen and tender joints, visual analog scale for global health, and erythrocyte sedimentation rate (ESR)] was evaluated at baseline and regularly for 24 months. Radiographs of hands and feet were graded using the Larsen score.

    RESULTS: Patients with anti-MCV antibodies had significantly less reduction in Disease Activity Score (DAS28) over time (p < 0.01), and significantly increased area under the curve (AUC) for DAS28 (p < 0.05), ESR (p < 0.01), C-reactive protein (p < 0.01), and swollen joint count (p = 0.057) compared to those without. Corresponding differences were not found in patients with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression (p < 0.0001-0.01) and radiological outcome (p < 0.0001-0.01) at 24 months were significantly predicted by all ACPA after baseline adjustments. PTPN22 T variant and HLA-DRB1 alleles were not related to radiological progression or inflammatory activity over time.

    CONCLUSION: Anti-MCV antibodies are associated with a more severe RA disease, as measured by DAS28, ESR, and swollen joint count over time, compared with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression was predicted equally by all 4 autoantibodies.

  • 19.
    Kelderer, Fanny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Mogren, Ingrid
    Department of Clinical Sciences, Obstetrics and Gynecology, Umeå, Sweden.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Silfverdal, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    West, Christina E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Associations between pre- and postnatal antibiotic exposures and early allergic outcomes: a population-based birth cohort study2022Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 33, nr 9, artikel-id e13848Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Early life antibiotic treatment is one likely exposure influencing allergy risk. The objective was to investigate associations between pre- and postnatal antibiotic exposures and the development of allergic manifestations until age 18 months.

    Methods: We included 1387 mother–child dyads from the prospective, population-based NorthPop birth cohort study. Data on antibiotic exposures in pregnancy and childhood were collected by web-based questionnaires. Until the child turned 18 months old, parents (n = 1219) reported symptoms of wheeze, eczema, and physician-diagnosed asthma; parents (n = 1025) reported physician-diagnosed food allergy. At age 18 months, serum immunoglobulin E levels to inhalant (Phadiatop) and food (Food mix fx5) allergens were determined. Associations were estimated using bivariable and multivariable logistic regressions.

    Results: Prenatal antibiotic exposure was positively associated with food sensitization in the crude (OR 1.82, 95% CI 1.01–3.26) but not in the adjusted analyses (aOR 1.58, 0.82–3.05). A borderline significant association was found between prenatal exposure and wheeze (aOR 1.56, 0.95–2.57). Postnatal antibiotics were positively associated with wheeze (aOR 2.14, 1.47–3.11), asthma (aOR 2.35, 1.32–4.19), and eczema (aOR 1.49, 1.07–2.06). Postnatal antibiotics were negatively associated with food sensitization (aOR 0.46, 95% CI 0.25–0.83) but not with food allergy nor sensitization to inhalants.

    Conclusion: Pre- and postnatal antibiotic exposure demonstrated positive associations with allergic manifestations and the former also with food sensitization. In contrast, there was a negative association between postnatal antibiotics and food sensitization. Food sensitization is often transient but may precede respiratory allergies. Future studies should investigate the relationship between antibiotic exposure and food sensitization later in childhood.

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  • 20.
    Lundberg, Veronica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Coyne, Imelda
    School of Nursing & Midwifery, Trinity College Dublin, Dublin, Ireland.
    Fjellman-Wiklund, Anncristine
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    How children with juvenile idiopathic arthritis experience participation and communication in healthcare encounters: Children’s, young adults’ and parents’ viewsManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Children report that they do not participate in their healthcare as much as they want, despite having the lawful right to form their own views and the right to express those views freely in all matters affecting themselves. Children and parents are more satisfied when healthcare professionals (HCP) use a participatory style in healthcare encounters.

    Aim: The aim was to explore children and young adults with Juvenile Idiopathic Arthritis (JIA) experiences and parents of children with JIA about the children´s participation and communication with healthcare professionals.

    Methods: A qualitative study design was used, with participatory workshops, held separately for children and young adults with JIA and parents of children with JIA. The workshop data were analysed with Graneheim and Lundman’s Qualitative Content Analysis (QCA) framework resulting in one main theme and two subthemes. 

    Results: The theme “Moving from alienation to familiarity with healthcare encounters” illustrates how the children needed extra support from healthcare professionals (HCPs) and their parents to be able to participate. They needed to feel safe, understood and respected by the HCPs and they wanted to receive the help they needed. The subtheme “Distancing oneself from healthcare” describes why children felt reluctant to engage in the healthcare encounters and experienced difficulty expressing how they really felt. The subtheme “Being a normal event in life” explains how children felt more comfortable in healthcare over time when they knew what would happen, and felt that HCP gave them the support they needed to participate.

    Conclusions: Children’s participation in healthcare encounters varied depending on if children felt alienation or familiar to the healthcare situations. Children distance themselves and are reluctant to healthcare encounters if they find them emotionally distressing and feel disregarded. In time children can become more familiar and at ease with healthcare situations when they feel safe and experience personal and positive encounters. When the children are prepared for the encounter, provided with the space and support they want and receive tailored help they are more enabled to participate.

  • 21.
    Lundberg, Veronica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Coyne, Imelda
    School of Nursing & Midwifery, Trinity College Dublin, Dublin, Ireland.
    Fjellman-Wiklund, Anncristine
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    How children with juvenile idiopathic arthritis view participation and communication in healthcare encounters: a qualitative study2021Ingår i: Pediatric Rheumatology, E-ISSN 1546-0096, Vol. 19, nr 1, artikel-id 156Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Children report that they do not participate in their healthcare as much as they want, despite having the lawful right to form their own views and the right to express those views freely in all matters affecting them. Children and parents appeared to be more satisfied when healthcare professionals (HCP) use a participatory style in healthcare encounters.

    Aim: To explore how children, adolescents and young adults with Juvenile Idiopathic Arthritis (JIA) and parents of children with JIA view their participation and communication in healthcare encounters with healthcare professionals.

    Methods: Using a qualitative study design, participatory workshops were held separately for children and young adults with JIA and parents of children with JIA. The workshop data were analysed with Graneheim and Lundman’s Qualitative Content Analysis resulting in one main theme and two subthemes.

    Results: The theme “Feeling alienated or familiar with healthcare encounters” illuminates how children felt alienated at healthcare encounters if they found the encounters emotionally distressing. Children could withhold information regarding their health and function from both HCPs and their family and friends. The subtheme “Distancing oneself from healthcare” describe why children felt reluctant to engage in the healthcare encounters and experienced difficulty expressing how they really felt. The subtheme “Being a normal event in life” describe how children felt more comfortable over time engaging with HCPs when they knew what would happen, and felt that HCPs gave them the necessary support they needed to participate. Conclusions: Children’s participation in healthcare encounters varied depending if children felt alienated or familiar to the healthcare situations. Children distance themselves and are reluctant to engage in healthcare encounters if they find them emotionally distressing and feel disregarded. Over time, children can become more familiar and at ease with healthcare situations when they feel safe and experience personal and positive encounters. When the children are prepared for the encounter, provided with the space and support they want and receive tailored help they are more enabled to participate.

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  • 22.
    Lundberg, Veronica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lindh, Viveca
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Petersen, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Eurenius, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Health-related quality of life in girls and boys with juvenile idiopathic arthritis: self- and parental reports in a cross-sectional study2012Ingår i: Pediatric Rheumatology, E-ISSN 1546-0096, Vol. 10, artikel-id 33Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Juvenile Idiopathic Arthritis (JIA) affects children and adolescents with both short-term and long-term disability. These children also report lower health-related quality of life (HRQOL) compared to their healthy peers. However, there seems to be some discrepancies between self- and parent-reports, and gender differences need to be further studied. This study aims to describe HRQOL in girls and boys with JIA, and to explore gender differences in self-reports compared to parent-reports of HRQOL in children with JIA.

    Methods: Fifty-three children and adolescents with JIA (70% girls and 30% boys) with a median age of 14 years (8–18 years), and their parents, participated in this cross-sectional study in Sweden. Data was systematically collected prior to ordinary visits at a Pediatric outpatient clinic, during a period of 16 months (2009–2010). Disability was assessed with the Childhood Health Assessment Questionnaire (CHAQ), and disease activity by physicians’ assessments and Erythrocyte Sedimentation Rate (ESR). The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) was used to assess self- and parent-reports of HRQOL in the child.

    Results: In this sample of children with generally low disease activity and mild to moderate disability, more than half of the children experienced suboptimal HRQOL, equally in girls and boys. Significant differences between self- and parent-reports of child HRQOL were most evident among girls, with lower parent-reports regarding the girl’s physical- and psychosocial health as well as in the total HRQOL score. Except for the social functioning subscale, where parents’ reports were higher compared to their sons, there were no significant differences between boys- and parent-reports.

    Conclusions: More than half of the girls and boys experienced suboptimal HRQOL in this sample, with no gender differences. However, there were differences between self- and parent-reports of child HRQOL, with most significant differences found among the girls. Thus, differences between self- and parent-reports of child HRQOL must be taken into account in clinical settings, especially among girls with JIA.

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  • 23.
    Lundberg, Veronica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Sandlund, Marlene
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Janols, Rebecka
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fjellman-Wiklund, Anncristine
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    How children and adolescents with juvenile idiopathic arthritis participate in their healthcare: health professionals' views2022Ingår i: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 44, nr 10, s. 1908-1915Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The study explores how healthcare professionals view participation of children and adolescents with juvenile idiopathic arthritis, in healthcare encounters.

    Methods: This qualitative study includes focus groups of HCPs from different professions. The interviews were analysed with qualitative content analysis.

    Results: The theme “Creating an enabling arena” illuminates how HCPs face possibilities and challenges when enabling children to communicate and participate in clinical encounters. HCPs, parents, and the healthcare system need to adjust to the child. The sub-theme “Bringing different perspectives” describes how children and their parents cooperate and complement each other during healthcare encounters. The sub-theme “Building a safe and comfortable setting” includes how HCPs address the child’s self-identified needs and make the child feel comfortable during encounters. The sub-theme “Facilitating methods in a limiting organisation” includes how HCPs’ working methods and organization may help or hinder child participation during encounters.

    Conclusions: HCPs encourage children and adolescents to make their views known during healthcare encounters by creating an enabling arena. Collaboration and building good relationships between the child, the parents and the HCPs, before and during the healthcare encounters, can help the child express their wishes and experiences. Clinical examinations and use of technology, such as photos, films and web-bases questionnaires can be a good start for a better child communication in healthcare encounters.

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  • 24.
    Lundberg, Veronica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sandlund, Marlene
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Janols, Rebecka
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fjellman-Wiklund, Anncristine
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    How children with juvenile idiopathic arthritis participate in their healthcare: Health professionals' viewsManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: This study explores how juvenile idiopathic arthritis (JIA) teams experience participation of children with arthritis in their own healthcare.

    Methods: This qualitative study includes focus groups of HCPs from different professions. The interviews were analysed with qualitative content analysis.

    Results: The theme “Creating an enabling arena” illuminates how HCPs face possibilities and challenges when enabling children to communicate and participate in clinical encounters. HCPs, parents, and the healthcare system need to adjust to the child. The sub-theme “Children and parents bring different perspectives” describes how children and their parents cooperate and complement each other during healthcare encounters. The sub-theme “Building a comfortable setting” includes how HCPs address the child’s self-identified needs and make the child feel comfortable during encounters. The sub-theme “Facilitating methods in a limiting system” includes how HCPs’ working methods and organization may help or hinder child participation during encounters.

    Conclusions: Using age-appropriate explanations, HCPs encourage children to express their everyday challenges. Collaboration between children and parents before a healthcare encounter and between children, parents, and HCPs during an encounter help children express their wishes and experiences. HCPs enable child participation by creating a good relationship with the children and their parents and by strengthening the children’s confidence and autonomy. 

  • 25. Sack, Ulrich
    et al.
    Bossuyt, Xavier
    Andreeva, Hristina
    Antal-Szalmas, Peter
    Bizzaro, Nicola
    Bogdanos, Dimitrios
    Borzova, Elena
    Conrad, Karsten
    Dragon-Durey, Marie-Agnes
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Fischer, Katarzyna
    Haapala, Anna-Maija
    Heijnen, Ingmar
    Herold, Manfred
    Klotz, Werner
    Kozmar, Ana
    Kuna, Andrea Tesija
    Hoyos, Marcos Lopez
    Malkov, Vladimir A.
    Musset, Lucile
    Nagy, Eszter
    Roennelid, Johan
    Shoenfeld, Yehuda
    Sundic, Tatjana
    Tsirogianni, Alexandra
    Uibo, Raivo
    Rego Sousa, Maria Jose
    Damoiseaux, Jan
    Quality and best practice in medical laboratories: specific requests for autoimmunity testing2020Ingår i: Autoimmun Highlights, ISSN 2038-0305, Vol. 11, nr 1, artikel-id 12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Special conditions associated with laboratory autoimmune testing are not well compatible with recent developments in regulatory frameworks such as EN/ISO 15189 accreditation or in vitro diagnostic medical device regulation (IVD-R). In addition, international recommendations, guidelines and disease criteria are poorly defined with respect to requirements on autoantibody testing. Laboratory specialists from Austria, Belgium, Croatia, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, and The Netherlands collected information, reported national experience, and identified quality issues in relation to autoantibody testing that require consensus on interpretation of the regulatory frameworks and guidelines. This process has been organized by the European Autoimmunity Standardisation Initiative (EASI). By identifying the critical items and looking for a consensus, our objective was to define a framework for, in particular, EN/ISO accreditation purposes. Here, we present a review of current publications and guidelines in this field to unify national guidelines and deliver in this way a European handout on quality control and accreditation for laboratories involved in autoantibody testing. We focus on quality items that can be checked during accreditation visits. Despite various local varieties, we encountered an overwhelming dedication to quality assurance in all contributing countries.

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  • 26. Sandling, Johanna K
    et al.
    Garnier, Sophie
    Sigurdsson, Snaevar
    Wang, Chuan
    Nordmark, Gunnel
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Padyukov, Leonid
    Sturfelt, Gunnar
    Jönsen, Andreas
    Bengtsson, Anders A
    Truedsson, Lennart
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Mälarstig, Anders
    Strawbridge, Rona J
    Hamsten, Anders
    Criswell, Lindsey A
    Graham, Robert R
    Behrens, Timothy W
    Eloranta, Maija-Leena
    Alm, Gunnar
    Rönnblom, Lars
    Syvänen, Ann-Christine
    A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE2011Ingår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 19, nr 4, s. 479-484Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P(meta)=0.00010 and P(meta)=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P(meta)=3.3 × 10(-5)), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis.

  • 27.
    Siljehult, Filip
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Concentrations of infliximab and anti-drug antibodies in relation to clinical response in patients with rheumatoid arthritis2018Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, nr 5, s. 345-350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The efficacy of anti-tumour necrosis factor-α (anti-TNF-α) treatment with infliximab (IFX) may be reduced by the development of anti-drug antibodies (ADAs). This study evaluated drug concentration and the presence of ADAs, relative to response, in rheumatoid arthritis (RA) patients treated with IFX.

    Method: Ninety-four RA patients were consecutively included and assessed for disease activity at baseline, and after 14, and 30 or 52 weeks. Serum IFX concentration and ADAs were analysed using in-house enzyme-linked immunosorbent assays. ADA analysis was based on binding to TNF-α-coated plates, with the lower detection limit set at mean + 2 sd of controls.

    Results: At 14 and 52 weeks, 74.5% of the patients had moderate to good response. Good responders had significantly higher IFX concentrations than moderate and poor responders at 52 weeks (6.6 ± 1.4 µg/mL vs 3.6 ± 1.3 µg/mL and 2.6 ± 1.6 µg/mL, respectively). An IFX concentration ≥4.66 µg/mL at 14 weeks yielded a moderate to good response at 30/52 weeks, with 91.3% specificity and 39.3% sensitivity. Eleven patients dropped out owing to lack of efficacy and eight owing to side effects; three with IFX concentration ≤ 0.5 µg/mL were ADA positive. At an IFX concentration ≤ 0.5 µg/mL, 43.8% and 30.1% at 14 and 52 weeks, respectively, were ADA positive. None of the good responders had ADAs.

    Conclusion: One-quarter of patients had an IFX concentration ≤ 0.5 µg/mL but only 11.7% had ADAs. High IFX concentration was related to a good response, suggesting that the lack of response could be due to a lack of IFX, rather than to the presence of ADAs.

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  • 28.
    Södergren, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Boman, Kurt
    Department of Medicine, Skellefteå Hospital, Lasarettsvägen, Skellefteå.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Lundström, Elisabet
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Smedby, Torgny
    Department of Rheumatology, Östersund Hospital, Kyrkgatan, 831 83 Östersund, Sweden.
    Söderlund, Lisbet
    Department of Rheumatology, Sunderby Hospital, 971 80 Luleå, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wållberg-Jonsson, Solveig
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness2010Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 12, nr 4, s. R158-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION : In this study we aimed to investigate whether there are indications of premature atherosclerosis, as measured by endothelial dependent flow-mediated dilation (ED-FMD) and intima media thickness (IMT), in patients with very early RA, and to analyze its relation to biomarkers of endothelial dysfunction, taking inflammation and traditional cardiovascular disease (CVD) risk factors into account.

    METHODS : Patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study of CVD co-morbidity. Of these, all patients aged ≤60 years were consecutively included in this survey of CVD risk factors (n = 79). Forty-four age and sex matched controls were included. IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography. Blood was drawn for analysis of lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA)-mass, VonWillebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), sE-selectin, sL-selectin and monocyte chemotactic protein-1 (MCP-1). In a subgroup of 27 RA patients and their controls the ultrasound measurements were reanalysed after 18 months.

    RESULTS : There were no significant differences between RA patients and controls in terms of IMT or ED-FMD at the first evaluation. However after 18 months there was a significant increase in the IMT among the patients with RA (P < 0.05). Patients with RA had higher levels of VWF, sICAM-1 (P < 0.05) and of MCP-1 (P = 0.001) compared with controls. In RA, IMT was related to some of the traditional CVD risk factors, tPA-mass, VWF (P < 0.01) and MCP-1 and inversely to sL-selectin (P < 0.05). In RA, ED-FMD related to sL-selectin (P < 0.01). DAS28 at baseline was related to PAI-1, tPA-mass and inversely to sVCAM-1 (P < 0.05) and sL-selectin (P = 0.001).

    CONCLUSIONS : We found no signs of atherosclerosis in patients with newly diagnosed RA compared with controls. However, in patients with early RA, IMT and ED-FMD were, to a greater extent than in controls, related to biomarkers known to be associated with endothelial dysfunction and atherosclerosis. After 18 months, IMT had increased significantly in RA patients but not in controls.

  • 29. Van Hoovels, Lieve
    et al.
    Broeders, Sylvia
    Chan, Edward K. L.
    Andrade, Luis
    de Melo Cruvinel, Wilson
    Damoiseaux, Jan
    Viander, Markku
    Herold, Manfred
    Coucke, Wim
    Heijnen, Ingmar
    Bogdanos, Dimitrios
    Calvo-Alen, Jaime
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Kozmar, Ana
    Kuhi, Liisa
    Bonroy, Carolien
    Lauwerys, Bernard
    Schouwers, Sofie
    Lutteri, Laurence
    Vercammen, Martine
    Mayer, Miroslav
    Patel, Dina
    Egner, William
    Puolakka, Kari
    Tesija-Kuna, Andrea
    Shoenfeld, Yehuda
    de Sousa, Maria Jose Rego
    Hoyos, Marcos Lopez
    Radice, Antonella
    Bossuyt, Xavier
    Current laboratory and clinical practices in reporting and interpreting anti-nuclear antibody indirect immunofluorescence (ANA IIF) patterns: results of an international survey2020Ingår i: AUTOIMMUNITY HIGHLIGHTS, ISSN 2038-0305, Vol. 11, nr 1, artikel-id 17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) has recently proposed nomenclature in order to harmonize ANA indirect immunofluorescence (IIF) pattern reporting. ICAP distinguishes competent-level from expert-level patterns. A survey was organized to evaluate reporting, familiarity, and considered clinical value of ANA IIF patterns. Methods Two surveys were distributed by European Autoimmunity Standardization Initiative (EASI) working groups, the International Consensus on ANA Patterns (ICAP) and UK NEQAS to laboratory professionals and clinicians. Results 438 laboratory professionals and 248 clinicians from 67 countries responded. Except for dense fine speckled (DFS), the nuclear competent patterns were reported by > 85% of the laboratories. Except for rods and rings, the cytoplasmic competent patterns were reported by > 72% of laboratories. Cytoplasmic IIF staining was considered ANA positive by 55% of clinicians and 62% of laboratory professionals, with geographical and expertise-related differences. Quantification of fluorescence intensity was considered clinically relevant for nuclear patterns, but less so for cytoplasmic and mitotic patterns. Combining IIF with specific extractable nuclear antigens (ENA)/dsDNA antibody testing was considered most informative. Of the nuclear competent patterns, the centromere and homogeneous pattern obtained the highest scores for clinical relevance and the DFS pattern the lowest. Of the cytoplasmic patterns, the reticular/mitochondria-like pattern obtained the highest scores for clinical relevance and the polar/Golgi-like and rods and rings patterns the lowest. Conclusion This survey confirms that the major nuclear and cytoplasmic ANA IIF patterns are considered clinically important. There is no unanimity on classifying DFS, rods and rings and polar/Golgi-like as a competent pattern and on reporting cytoplasmic patterns as ANA IIF positive.

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  • 30. Wang, Chuan
    et al.
    Ahlford, Annika
    Järvinen, Tiina M
    Nordmark, Gunnel
    Eloranta, Maija-Leena
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Padyukov, Leonid
    Sturfelt, Gunnar
    Jönsen, Andreas
    Bengtsson, Anders A
    Truedsson, Lennart
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sjöwall, Christopher
    Julkunen, Heikki
    Criswell, Lindsey A
    Graham, Robert R
    Behrens, Timothy W
    Kere, Juha
    Rönnblom, Lars
    Syvänen, Ann-Christine
    Sandling, Johanna K
    Genes identified in Asian SLE GWASs are also associated with SLE in Caucasian populations2013Ingår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 21, nr 9, s. 994-999Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent genome-wide association studies (GWASs) conducted in Asian populations have identified novel risk loci for systemic lupus erythematosus (SLE). Here, we genotyped 10 single-nucleotide polymorphisms (SNPs) in eight such loci and investigated their disease associations in three independent Caucasian SLE case-control cohorts recruited from Sweden, Finland and the United States. The disease associations of the SNPs in ETS1, IKZF1, LRRC18-WDFY4, RASGRP3, SLC15A4, TNIP1 and 16p11.2 were replicated, whereas no solid evidence of association was observed for the 7q11.23 locus in the Caucasian cohorts. SLC15A4 was significantly associated with renal involvement in SLE. The association of TNIP1 was more pronounced in SLE patients with renal and immunological disorder, which is corroborated by two previous studies in Asian cohorts. The effects of all the associated SNPs, either conferring risk for or being protective against SLE, were in the same direction in Caucasians and Asians. The magnitudes of the allelic effects for most of the SNPs were also comparable across different ethnic groups. On the contrary, remarkable differences in allele frequencies between Caucasian and Asian populations were observed for all associated SNPs. In conclusion, most of the novel SLE risk loci identified by GWASs in Asian populations were also associated with SLE in Caucasian populations. We observed both similarities and differences with respect to the effect sizes and risk allele frequencies across ethnicities.

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