umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Rantapää-Dahlqvist, SolbrittORCID iD iconorcid.org/0000-0001-8259-3863
Alternative names
Publications (10 of 328) Show all publications
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
Show others...
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
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
Show others...
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: 2019-02-27Bibliographically 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
Show others...
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
Medicine, 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: 2018-08-07Bibliographically approved
Wibetoe, G., Sexton, J., Ikdahl, E., Rollefstad, S., Kitas, G., van Riel, P., . . . Semb, A. G. (2018). Cardiovascular risk age and vascular age estimations in predicting cardiovascular events in rheumatoid arthritis patients. Paper presented at Congress of the European-League-Against-Rheumatism (EULAR), JUN 13-16, 2018, Amsterdam, NETHERLANDS. Annals of the Rheumatic Diseases, 77, 1743-1743
Open this publication in new window or tab >>Cardiovascular risk age and vascular age estimations in predicting cardiovascular events in rheumatoid arthritis patients
Show others...
2018 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, p. 1743-1743Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-152914 (URN)000444351005290 ()
Conference
Congress of the European-League-Against-Rheumatism (EULAR), JUN 13-16, 2018, Amsterdam, NETHERLANDS
Note

Supplement: 2

Meeting Abstract: AB1301

Available from: 2018-10-30 Created: 2018-10-30 Last updated: 2018-10-30Bibliographically approved
Eriksson, D., Bianchi, M., Landegren, N., Dalin, F., Skov, J., Hultin-Rosenberg, L., . . . Kämpe, O. (2018). Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison's disease in Sweden. Scientific Reports, 8, Article ID 8395.
Open this publication in new window or tab >>Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison's disease in Sweden
Show others...
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8395Article in journal (Refereed) Published
Abstract [en]

Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

National Category
Endocrinology and Diabetes Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-149017 (URN)10.1038/s41598-018-26842-2 (DOI)000433538800022 ()29849176 (PubMedID)2-s2.0-85047930642 (Scopus ID)
Available from: 2018-06-15 Created: 2018-06-15 Last updated: 2018-06-15Bibliographically approved
Siljehult, F., Ärlestig, L., Eriksson, C. & Rantapää-Dahlqvist, S. (2018). Concentrations of infliximab and anti-drug antibodies in relation to clinical response in patients with rheumatoid arthritis. Scandinavian Journal of Rheumatology, 47(5), 345-350
Open this publication in new window or tab >>Concentrations of infliximab and anti-drug antibodies in relation to clinical response in patients with rheumatoid arthritis
2018 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, no 5, p. 345-350Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-150975 (URN)10.1080/03009742.2018.1433232 (DOI)000443912500001 ()29701536 (PubMedID)2-s2.0-85046006206 (Scopus ID)
Available from: 2018-08-21 Created: 2018-08-21 Last updated: 2018-10-25Bibliographically approved
Imgenberg-Kreuz, J., Almlof, J. C., Leonard, D., Alexsson, A., Nordmark, G., Eloranta, M.-L., . . . Sandling, J. K. (2018). DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus. Annals of the Rheumatic Diseases, 77(5), 736-743
Open this publication in new window or tab >>DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus
Show others...
2018 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 5, p. 736-743Article in journal (Refereed) Published
Abstract [en]

Objectives Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with heterogeneous presentation and complex aetiology where DNA methylation changes are emerging as a contributing factor. In order to discover novel epigenetic associations and investigate their relationship to genetic risk for SLE, we analysed DNA methylation profiles in a large collection of patients with SLE and healthy individuals. Methods DNA extracted from blood from 548 patients with SLE and 587 healthy controls were analysed on the Illumina HumanMethylation 450 k BeadChip, which targets 485 000 CpG sites across the genome. Single nucleotide polymorphism (SNP) genotype data for 196 524 SNPs on the Illumina ImmunoChip from the same individuals were utilised for methylation quantitative trait loci (cis-meQTLs) analyses. Results We identified and replicated differentially methylated CpGs (DMCs) in SLE at 7245 CpG sites in the genome. The largest methylation differences were observed at type I interferon-regulated genes which exhibited decreased methylation in SLE. We mapped cis-meQTLs and identified genetic regulation of methylation levels at 466 of the DMCs in SLE. The meQTLs for DMCs in SLE were enriched for genetic association to SLE, and included seven SLE genome-wide association study (GWAS) loci: PTPRC (CD45), MHC-class III, UHRF1BP1, IRF5, IRF7, IKZF3 and UBE2L3. In addition, we observed association between genotype and variance of methylation at 20 DMCs in SLE, including at the HLADQB2 locus. Conclusions Our results suggest that several of the genetic risk variants for SLE may exert their influence on the phenotype through alteration of DNA methylation levels at regulatory regions of target genes.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-150711 (URN)10.1136/annrheumdis-2017-212379 (DOI)000430492600020 ()29437559 (PubMedID)2-s2.0-85046359601 (Scopus ID)
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-17Bibliographically approved
Westra, H.-J., Martinez-Bonet, M., Onengut-Gumuscu, S., Lee, A., Luol, Y., Teslovich, N., . . . Raychaudhuri, S. (2018). Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes. Nature Genetics, 50(10), 1366-+
Open this publication in new window or tab >>Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes
Show others...
2018 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 10, p. 1366-+Article in journal (Refereed) Published
Abstract [en]

To define potentially causal variants for autoimmune disease, we fine-mapped(1,2) 76 rheumatoid arthritis (11,475 cases,15,870 controls)(3) and type 1 diabetes loci (9,334 cases, 11,111 controls)(4). After sequencing 799 1-kilobase regulatory (H3K4me3) regions within these loci in 568 individuals, we observed accurate imputation for 89% of common variants. We defined credible sets of <= 5 causal variants at 5 rheumatoid arthritis and 10 type 1 diabetes loci. We identified potentially causal missense variants at DNASE1L3, PTPN22, SH2B3, and TYK2, and noncoding variants at MEG3, CD28-CTLA4, and IL2RA. We also identified potential candidate causal variants at SIRPG and TNFAIP3. Using functional assays, we confirmed allele-specific protein binding and differential enhancer activity for three variants: the CD28-CTLA4 rs117701653 SNP, MEG3 rs34552516 indel, and TNFAIP3 rs35926684 indel.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-152883 (URN)10.1038/s41588-018-0216-7 (DOI)000446047000008 ()30224649 (PubMedID)
Funder
NIH (National Institute of Health), P30 AR070253NIH (National Institute of Health), R01 AR065538
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2018-10-31Bibliographically approved
Bjorsenius, I., Rantapää-Dahlqvist, S., Wållberg-Jonsson, S. & Södergren, A. (2018). Increased progression of atherosclerosis in patients with rheumatoid arthritis is partially reflected by disease severity at the time of diagnosis: 11-year prospective follow-up. Scandinavian Journal of Rheumatology, 47, 20-21
Open this publication in new window or tab >>Increased progression of atherosclerosis in patients with rheumatoid arthritis is partially reflected by disease severity at the time of diagnosis: 11-year prospective follow-up
2018 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 20-21Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-151574 (URN)000442295400032 ()
Note

Supplement: 129

Meeting Abstract: PP15

Available from: 2018-09-07 Created: 2018-09-07 Last updated: 2018-09-07Bibliographically approved
Johansson, L., Kindstedt, E., Palmqvist, P., Holm, C. K., Kokkonen, H., Johansson, I., . . . Rantapää-Dahlqvist, S. (2018). Marginal jawbone loss is associated with onset of rheumatoid arthritis and is related to plasma level of receptor activator of nuclear factor kappa-B ligand. Scandinavian Journal of Rheumatology, 47, 22-22
Open this publication in new window or tab >>Marginal jawbone loss is associated with onset of rheumatoid arthritis and is related to plasma level of receptor activator of nuclear factor kappa-B ligand
Show others...
2018 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 22-22Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-151577 (URN)000442295400034 ()
Note

Supplement: 129

Meeting Abstract: PP17

Available from: 2018-09-07 Created: 2018-09-07 Last updated: 2018-09-07Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8259-3863

Search in DiVA

Show all publications