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Rantapää-Dahlqvist, SolbrittORCID iD iconorcid.org/0000-0001-8259-3863
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Publications (10 of 335) Show all publications
Lindquist, S., Alenius, G.-M., Berntson, L., Rantapää-Dahlqvist, S., Lundberg, L., Wang, Y. & Hernell, O. (2019). A novel target for treatment of inflammatory joint diseases. Paper presented at Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019. Annals of the Rheumatic Diseases, 78, 1525-1526
Open this publication in new window or tab >>A novel target for treatment of inflammatory joint diseases
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2019 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, p. 1525-1526Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: The bile salt-stimulated lipase (BSSL) is a hitherto unrecognized player in inflammation. Animals devoid of BSSL (knockout mice) are protected from developing collagen induced arthritis (CIA) and collagen antibody induced arthritis (CAIA), and antibodies directed towards BSSL has been proven to prevent or mitigate arthritis in mouse and rat arthritis models1. In humans, BSSL is present in blood2 and accumulate at sites of inflammation. Patients with acute pancreatitis have significantly increased plasma BSSL levels compared to healthy controls. Whether BSSL in blood originates from pancreas, inflammatory cells, or both remains to be elucidated.

Objectives: To determine BSSL concentration in blood samples from patients with inflammatory joint disorders and to evaluate possible relationships between circulating BSSL levels and disease-activity variables.

Methods: BSSL concentrations in plasma or serum were determined in patients with rheumatoid arthritis (RA), psoriasis arthritis (PsA), and juvenile idiopathic arthritis (JIA) by a sandwich enzyme-linked immunosorbent assay (ELISA). Correlations between BSSL concentrations and disease activity score, erythrocyte sedimentation rate (ESR), blood levels of C-reactive protein (CRP), S100A8/9, leukocyte- and neutrophil counts, proinflammatory cytokines and chemokines were analyzed using Spearman rank-order correlation.

Results: Significant correlations between BSSL concentration in plasma and disease activity score (DAS28, rS=0.31, p=0.007), ESR (rS=0.58, p<0.000), CRP (rS=0.42, p=0.012), leukocytes (rS=0.66, p<0.000), and neutrophils (rS=0.71, p<0.000) were found in RA. The BSSL plasma concentration decreased with duration of treatment with the TNFα inhibitor infliximab, in parallel with decreasing DAS28 score.

BSSL concentration was significantly higher in sera from PsA patients with both oligo- and polyarthritis compared with healthy controls. Moreover, BSSL concentration in serum correlated significantly with S100A8/A9 and CRP concentrations (rS=0.54, p<0.001 and rS=0.49, p<0.001, respectively). No correlation between levels of BSSL and cytokines or chemokines were found in RA or PsA plasma or serum, respectively.

In JIA, levels of BSSL in serum correlated significantly with JIA disease activity score (JADAS27) (rS=0.26, p=0.007), ESR (rS=0.47, p<0.000), and leukocytes (rS=0.32, p<0.000).

Conclusion: BSSL concentration in serum and plasma correlated with disease activity in patients with inflammatory joint disorders, i.e. RA, PsA and JIA. These data in humans support the relevance of our previous studies in rodents and therefore also our hypothesis 1 that BSSL is a novel target for treatment of inflammatory diseases.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-161720 (URN)10.1136/annrheumdis-2019-eular.2165 (DOI)000472207104460 ()
Conference
Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019
Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved
Farias, F. H. G., Dahlqvist, J., Kozyrev, S. V., Leonard, D., Wilbe, M., Abramov, S. N., . . . Lindblad-Toh, K. (2019). A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts. European Journal of Human Genetics, 27(3), 432-441
Open this publication in new window or tab >>A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts
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2019 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 27, no 3, p. 432-441Article in journal (Refereed) Published
Abstract [en]

Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted resequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0 .014 , CI = 1.1-10). Fisher's exact test revealed an association between the genetic variant and a triad of disease manifestations including Raynaud, anti-Ul-ribonucleoprotein (anti-RNP), and anti-Smith (anti-Sm) antibodies (p = 0.00037) among the patients. The DNA-binding activity of the allele was further studied by EMSA, reporter assays, and minigenes. The region has properties of an active cell-specific enhancer, differentially affected by the alleles of rs200395694:G > T. In addition, the risk allele exerts an inhibitory effect on the splicing of the alternative tissue-specific isoform, and thus may modify the target gene set regulated by this isoform. These findings emphasize the potential of dissecting traits of complex diseases and correlating them with rare risk alleles with strong biological effects.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-156863 (URN)10.1038/s41431-018-0297-x (DOI)000458626500013 ()30459414 (PubMedID)
Available from: 2019-03-12 Created: 2019-03-12 Last updated: 2019-03-12Bibliographically approved
Södergren, A., Karp, K., Bengtsson, C., Möller, B., Rantapää-Dahlqvist, S. & Wållberg-Jonsson, S. (2019). Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis. PLoS ONE, 14(8), Article ID e0220531.
Open this publication in new window or tab >>Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 8, article id e0220531Article in journal (Refereed) Published
Abstract [en]

Objectives: Patients with rheumatoid arthritis (RA) have an increased mortality and morbidity due to cardiovascular disease (CVD). In this prospective 5-year follow up of patients with RA, we analysed several biomarkers, known to be associated with atherosclerosis and/or inflammation in the general population. The aim of this study was to find out whether the RA-disease per se affect these biomarkers and if those could be associated with the progression of atherosclerosis, as measured by intima media thickness (IMT) among patients with early RA.

Methods: Patients from northern Sweden diagnosed with early RA, are consecutively recruited into an ongoing prospective study on CVD comorbidity. A subgroup of patients, aged ≤60 years (n = 71) was included for ultrasound measurements of IMT at inclusion (T0) and after 5 years (T5) together with age-sex-matched controls (n = 40). The patients were clinically assessed. Blood was analysed for lipids, ESR and CRP and several biomarkers known to be associated with atherosclerosis in the general population.

Results: At T0, the patients with RA had significantly lower levels of MIF and significantly higher levels of interleukin (IL)-18 and MIC-1 compared with controls. At T5, the patients with RA had significantly higher levels of pentraxin3, MIC-1, TNF-R2, ICAM-1, VCAM-1 and endostatin compared with controls. At T0 the levels of MPO correlated with DAS28, sCD40L with CRP and IL-18 with systolic blood pressure and Reynolds risk score. Using PLSR on a CVD-panel analysed with multiplex immunoassay, the patients with RA could be correctly classified into those who had a worsening in their IMT over the five years or not. Here, MMP3 was identified as influential.

Conclusions: This study indicates that the RA disease itself could affect several of the biomarkers in this study, and possibly also the processes involved in the development of atherosclerosis.

Place, publisher, year, edition, pages
Public Library of Science, 2019
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-164650 (URN)10.1371/journal.pone.0220531 (DOI)000484993600022 ()31381601 (PubMedID)2-s2.0-85070281863 (Scopus ID)
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-10-25Bibliographically approved
Zhang, Y., Johansson, L., Rudin, A., Carlsson, L., Rantapää-Dahlqvist, S. & Maglio, C. (2019). In overweight subjects, serum adiponectin predicts the development of rheumatoid arthritis independently of other adipokines. Paper presented at Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019. Annals of the Rheumatic Diseases, 78, 298-298
Open this publication in new window or tab >>In overweight subjects, serum adiponectin predicts the development of rheumatoid arthritis independently of other adipokines
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2019 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, p. 298-298Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Adipokines, such as adiponectin, leptin, resistin and visfatin, are cytokines produced by the adipose tissue and involved in metabolism and inflammation1 . Adiponectin is elevated in both serum and synovial fluid of subjects with rheumatoid arthritis (RA), suggesting a possible role of this adipokine in the pathogenesis of RA 2,3. Circulating levels of leptin, resistin, and visfatin are also higher in subjects with RA compared to controls 2,4.

Objectives: Aim of this study was to determine if adiponectin, leptin, resistin, and visfatin predict the development of RA.

Methods: Two nested-case control studies were performed including presymptomatic participants of two cohorts from Sweden: the Swedish Obese Subjects (SOS) study and a cohort of individuals identified within the Medical Biobank of northern Sweden. The SOS is a clinical trial including 4047 subjects with obesity6 . During a follow-up for up to 29 years, 92 subjects developed RA. Among those 92 subjects, 82 subjects with available serum at baseline were matched 1:5 with 410 subjects who did not develop RA during follow-up. Matching was based on baseline age, sex, body-mass index (BMI), bariatric surgery yes/no, year of inclusion, and smoking. A nested case-control study of 88 sex- and age-matched pairs was performed within the Medical Biobank of Northern Sweden using blood samples donated before the onset of the first RA symptoms. The pre-dating time before onset of symptoms of RA was 8.5±5.0 years7 . Baseline serum levels of adiponectin, leptin, resistin, and visfatin were measured using the Quantikine ELISA kit from R&D Systems (Wiesbaden, Germany). Visfatin could not be measured in the Biobank cohort, due to lack of serum. Both binary logistic as well as conditional logistic regression analyses were used to determine if adipokines were elevated years before the onset of RA.

Results: In a multivariable analysis including adiponectin, leptin, resistin, visfatin performed in the SOS cohort, serum adiponectin was associated with a higher risk for RA independently of other adipokines (Odds ratio, OR, 1.1, 95% confidence interval, CI, 1.0-1.1, p value=0.01). Leptin, resistin and visfatin levels were not associated with the risk of RA. In the Biobank cohort, no association between adipokines and risk for RA was detected. However, when stratifying the population according to BMI, in the subgroup having BMI>25 (n=109), adiponectin levels were associated with higher risk for RA (OR 1.2, 95% CI 1.0-1.36, p=0.03), independently of leptin and resistin levels. Virtually the same results were obtained in both the SOS and the Biobank cohorts when conditional logistic regression analysis was used.

Conclusion: Our results suggest that higher serum adiponectin levels predict the development of RA in subjects with overweight/obesity.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-161730 (URN)10.1136/annrheumdis-2019-eular.5314 (DOI)000472207100635 ()
Conference
Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019
Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved
Ljung, L., Wiberg, K., Ärlestig, L. & Rantapää-Dahlqvist, S. (2019). Low-energy fractures in rheumatoid arthritis - associations with genes and clinical characteristics. Paper presented at Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019. Annals of the Rheumatic Diseases, 78, 344-345
Open this publication in new window or tab >>Low-energy fractures in rheumatoid arthritis - associations with genes and clinical characteristics
2019 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, p. 344-345Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Patients with rheumatoid arthritis (RA) have increased risk of osteoporosis and low-energy fractures. Several genes associated with bone mineralization, osteoporosis or risk of fracture in the general population have been identified.

Objectives: To analyse the association between nine selected SNPs and the risk of low-energy fracture, taking clinical patient characteristics into account.

Methods: We identified a cohort of patients (n=896, 70% women, age at inclusion 60.0±14.8 years) with RA according to ACR criteria from the catchment area of the register of Umeå injury database, Umeå, Sweden, which enabled identification of low-energy fractures (n=254). The follow-up (mean 8.8±6.1 years, total 7928 person-years) started two years after RA diagnosis but not earlier than January 1, 1993 and ended at the first of December 31, 2011, death or the first low-energy fracture. Nine SNPs were analysed in all patients with available DNA-samples (n=667) using KASPTM genotyping assays (LGC genomics Ltd, Hoddesdon, UK): rs3801387 (WNT16), rs6666455 (SOAT), rs3736228 (LRP5), rs4796995 (FAM210A), rs4792909 (SOST), rs2062377 (TNFRSF11B/OPG), rs884205 (TNFRSF11A/RANK), rs9533090 (TNFSF11/RANKL), and rs1373004 (DKK1). Anti-CCP was analysed and clinical patient characteristics (duration of RA, ever smoking, disease activity the first two years after RA diagnosis, and joint erosions) were extracted from patient files. Associations between the risk of fracture and risk alleles in the cohort were evaluated using Kaplan-Meier curves (K-M) and Cox proportional hazards models: crude, adjusted for age and sex, and for clinical patient characteristics.

Results: The SNPs: rs1373004, rs4792909, and rs2062377 were associated with the risk of fracture in K-M analyses (Figure 1). For the other genes no significant associations were observed. Patients carrying the risk allele of rs1373004 (22.6% of the patients), or who were homozygous for the risk allele of SNP rs4792909 (38.6%), had a >50% higher risk of low-energy fracture compare to other patients, irrespectively of disease characteristics (Table 1). The association between rs2062377 and the risk of fracture was not independent of clinical patient characteristics (Table 1).

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-161726 (URN)10.1136/annrheumdis-2019-eular.4264 (DOI)000472207101052 ()
Conference
Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019
Note

Supplement: 2

Meeting Abstract: THU0143

Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved
Wahlin, B., Innala, L., Magnusson, S., Möller, B., Smedby, T., Rantapää-Dahlqvist, S. & Wållberg-Jonsson, S. (2019). Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis Is Not Superior to the ACC/AHA Risk Calculator. Journal of Rheumatology, 130-137
Open this publication in new window or tab >>Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis Is Not Superior to the ACC/AHA Risk Calculator
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2019 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, p. 130-137Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Cardiovascular (CV) risk estimation calculators for the general population do not perform well in patients with rheumatoid arthritis (RA). An RA-specific risk calculator has been developed, but did not perform better than a risk calculator for the general population when validated in a heterogeneous multinational cohort.

METHODS: In a cohort of patients with new-onset RA from northern Sweden (n = 665), the risk of CV disease was estimated by the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA) and the American College of Cardiology/American Heart Association algorithm (ACC/AHA). The ACC/AHA estimation was analyzed, both as crude data and when adjusted according to the recommendations by the European League Against Rheumatism (ACC/AHA × 1.5). ERS-RA was calculated using 2 variants: 1 from patient and physician reports of hypertension (HTN) and hyperlipidemia [ERS-RA (reported)] and 1 from assessments of blood pressure (BP) and blood lipids [ERS-RA (measured)]. The estimations were compared with observed CV events.

RESULTS: All variants of risk calculators underestimated the CV risk. Discrimination was good for all risk calculators studied. Performance of all risk calculators was poorer in patients with a high grade of inflammation, whereas ACC/AHA × 1.5 performed best in the high-inflammatory patients. In those patients with an estimated risk of 5-15%, no risk calculator performed well.

CONCLUSION: ERS-RA underestimated the risk of a CV event in our cohort of patients, especially when risk estimations were based on patient or physician reports of HTN and hyperlipidemia instead of assessment of BP and blood lipids. The performance of ERS-RA was no better than that of ACC/AHA × 1.5, and neither performed well in high-inflammatory patients.

Place, publisher, year, edition, pages
Journal of Rheumatology, 2019
Keywords
rheumatoid arthritis, cardiovascular disease, risk assessment
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-155600 (URN)10.3899/jrheum.171008 (DOI)000457479200004 ()30275258 (PubMedID)
Funder
Västerbotten County CouncilSwedish Rheumatism Association
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-04-12Bibliographically approved
Kissel, T., van Schie, K., Hafkenscheid, L., Lundquist, A., Scherer, H. U., Kokkonen, H., . . . Rantapää-Dahlqvist, S. (2019). Rising ACPA igg variable domain glycosylation pre-disease associates with an increase in autoantibody levels and the development of rheumatoid arthritis. Paper presented at Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019. Annals of the Rheumatic Diseases, 78, 249-250
Open this publication in new window or tab >>Rising ACPA igg variable domain glycosylation pre-disease associates with an increase in autoantibody levels and the development of rheumatoid arthritis
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2019 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, p. 249-250Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Anti-citrullinated protein antibodies (ACPA) are present in the majority of rheumatoid arthritis (RA) patients (60-70%) and play a pivotal role in disease development1. ACPA IgGs are unique in a way that they are abundantly N-glycosylated within their variable regions2. These variable domain (V-domain) glycans are found on over 90% of ACPAs present in sera from RA-patients3. To undergo N-linked glycosylation, a consensus sequence in the protein backbone is required (N-X-S/T, where X ≠ P)4. Recently, it was shown that the N-linked glycosylation sites in ACPA-IgG V-domains are introduced during somatic hypermutation and that the introduction of such sites likely conveys a selective advantage to ACPA expressing B-cells5. However, it is currently unknown, whether ACPA-expressing B-cells already introduced glycosylation-sites into their V-domains before disease onset or when ACPA-V-domain glycosylation occurs.

Objectives: Investigate the appearance of ACPA V-domain glycosylation in pre-symptomatic individuals and RA patients.

Methods In a case-control study, individuals (n=201) from the Medical Biobank, who were sampled before onset of symptoms (mean±SEM predating time; 5.8±0.3 years) (140 aCCP+ and 61 aCCP-), and after diagnosis of RA (n=99, 94 aCCP+ and 5 aCCP-) and randomly selected control samples (n=43, 3 aCCP+ and 40 aCCP-) were analyzed for their ACPA IgG V-domain glycosylation levels. ACPA IgGs were affinity purified, N-linked glycans released, and 2-AA labeled for further analysis using UHPLC6. Data calibration and integration was performed and a cut-off defined. Samples below the cut-off were determined as non-detectable and excluded from the analysis. The percentage V-domain glycosylation was calculated as described previously3. Statistical calculations were performed using SPSS.

Results: Our data indicated that ACPA IgG V-domain glycans are already present years before symptom onset, in pre-symptomatic individuals who subsequently will develop RA. Analysis of matched pairs showed a significant increase of ACPA V-domain glycosylation in RA patients compared to individuals pre-disease (p<0.001). The results showed that ACPA N-glycosylation was correlated with anti-CCP concentrations pre-disease (rs =0.504, p<0.001), while no such association can be found after RA onset. Further, V-domain glycosylation levels increase closer to symptom onset.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-161721 (URN)10.1136/annrheumdis-2019-eular.5341 (DOI)000472207100546 ()
Conference
Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019
Note

 Supplement: 2

Meeting Abstract: OP0333

Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved
Roelsgaard, I. K., Ikdahl, E., Rollefstad, S., Wibetoe, G., Esbensen, B. A., Kitas, G. D., . . . Semb, A. G. (2019). Smoking cessation in patients with RA is associated with reduced CVD event rates and improved lipid profiles and predicts lower RA disease activity. Paper presented at Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019. Annals of the Rheumatic Diseases, 78, 1121-1122
Open this publication in new window or tab >>Smoking cessation in patients with RA is associated with reduced CVD event rates and improved lipid profiles and predicts lower RA disease activity
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2019 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, p. 1121-1122Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-161736 (URN)10.1136/annrheumdis-2019-eular.792 (DOI)000472207103295 ()
Conference
Annual European Congress of Rheumatology (EULAR), Madrid, Spain, June 12-15, 2019
Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved
Kindstedt, E., Johansson, L., Palmqvist, P., Koskinen Holm, C., Kokkonen, H., Johansson, I., . . . Lundberg, P. (2018). Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL. Arthritis & Rheumatology, 70(4), 508-515
Open this publication in new window or tab >>Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL
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2018 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, no 4, p. 508-515Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.

Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme‐linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.

Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL‐positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.

Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL‐positive presymptomatic subjects compared with RANKL‐negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2018
National Category
Rheumatology and Autoimmunity
Research subject
rheumatology; Odontology
Identifiers
urn:nbn:se:umu:diva-146131 (URN)10.1002/art.40394 (DOI)000428697300005 ()29195021 (PubMedID)
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2019-05-20Bibliographically approved
Kindstedt, E., Johansson, L., Palmqvist, P., Koskinen Holm, C. & Kokkonen, H. (2018). Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL. Rheumatology, 70(4), 508-515
Open this publication in new window or tab >>Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL
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2018 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 70, no 4, p. 508-515Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.

Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme‐linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.

Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL‐positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.

Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL‐positive presymptomatic subjects compared with RANKL‐negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.

Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-143006 (URN)10.1002/art.40394 (DOI)000428697300005 ()29195021 (PubMedID)
Available from: 2017-12-14 Created: 2017-12-14 Last updated: 2019-05-21Bibliographically approved
Projects
Aetio-patogenetic factors of importance for development of rheumatoid arthritis, disease severity and co-morbidity, in particular cardio-vascular disease [2009-03388_VR]; Umeå UniversityAetio-patogenetic factors of importance for development of rheumatoid arthritis, disease severity and co-morbidity, in particular cardio-vascular disease [2012-04096_VR]; Umeå UniversityAetio-pathogenic factors of importance for development of rheumatoid arthritis and of disease progression. Analyses of prospective material from biobanks of northern Sweden. [2018-02551_VR]; Umeå University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8259-3863

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