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| 2. |
- Apel, Maria, et al.
(författare)
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Variants in RUNX3 Contribute to Susceptibility to Psoriatic Arthritis, Exhibiting Further Common Ground With Ankylosing Spondylitis
- 2013
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 65:5, s. 1224-1231
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Tidskriftsartikel (refereegranskat)abstract
- Objective Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome-wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome-wide significance levels of association in the initial analysis. Methods Twenty-one of 22 single-nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris. Results Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 x 108 by Cochran-Mantel-Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.151.33). Further analyses based on linkage disequilibrium (LD) at RUNX3 refined the most significant association to an LD block located in the first intron of one isoform. Weaker evidence for association was detected in German patients with psoriasis vulgaris (P = 5.89 x 102; OR 1.13 [95% CI 1.001.28]), indicating a role in the skin manifestations of psoriasis. Conclusion Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondyloarthritis, although its risk allele is independent from the one for PsA. RUNX-3 is involved in CD8+ T lymphocyte differentiation and is therefore a good candidate for involvement in PsA and psoriasis vulgaris as T cellmediated diseases.
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| 3. |
- Hansson, Claes, et al.
(författare)
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S-Calprotectin (S100A8/S100A9) : A Potential Marker of Inflammation in Patients with Psoriatic Arthritis
- 2014
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Ingår i: Clinical & Developmental Immunology. - : Hindawi Limited. - 1740-2522 .- 1740-2530. ; , s. 696415-
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 4. |
- Hüffmeier, Ulrike, et al.
(författare)
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Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 996-999
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Tidskriftsartikel (refereegranskat)abstract
- Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10⁻¹⁷). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10⁻³). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10⁻²⁰, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.
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| 5. |
- Isaksson, J., et al.
(författare)
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Screening and simple counselling affect traditional cardiovascular risk factors in patients with early rheumatoid arthritis
- 2014
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa Healthcare. - 0300-9742 .- 1502-7732. ; 43:Suppl. 127 Meeting Abstract PP234, s. 76-76
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) and increased mortality in CVD. The cause of this increase has not been completely established, but chronic inflammation is thought to play a role. Traditional cardiovascular risk factors also appear to be important and may be potentiated by this inflammation. The Swedish Society for Rheumatology (SRF) has developed a set of guidelines for screening and primary prevention of CVD in patients with RA. The aim of this study was to evaluate these guidelines in a clinical setting.Method: Forty-seven patients newly diagnosed with RA during 2012 at the Department of Rheumatology, University Hospital of Umeå were recruited. Three months after initial diagnosis of RA, patients were examined physically and blood samples were collected with regard to traditional cardiovascular risk factors according to the guidelines from the SRF. Tests of cardiorespiratory fitness were also performed. Additionally, patients received simple counselling regarding matters of diet, tobacco use and exercise from a nurse and a physiotherapist, respectively. The counselling session, based upon national guidelines from the National Food Agency and the Public Health Agency, was performed once per patient and lasted for approximately 45 minutes. A follow-up was performed 9 months after the first examination. This intervention was integrated into the clinic’s pre-existing early RA follow-up programme. The results were adjusted for disease activity and disability.Results: Among the 47 included patients, 45 reached the 9-month follow-up. Two were excluded because of delayed follow-up. Mean diastolic blood pressure decreased significantly from 80 to 77 mmHg (p < 0.05). Mean S-cholesterol decreased significantly from 5.5 to 5.2 mmol/L (p < 0.05). Mean ApoA1/ApoB decreased significantly from 0.73 to 0.65 (p < 0.05). In all the remaining variables (waist circumference, BMI, systolic blood pressure, LDL, HDL, triglycerides, FP-glucose), a clear decreasing trend could be observed (p > 0.05). Aerobic capacity according to Åstrand remained unchanged (p > 0.05).Conclusions: Several traditional risk factors for CVD were improved at the 9-month follow-up. This suggests that this model of screening according to the SRF guidelines and simple counselling according to national guidelines might be useful in primary prevention of CVD in patients with RA.
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| 6. |
- Juneblad, Kristina, et al.
(författare)
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Association between the PTPN22 +1858 C/T polymorphism and psoriatic arthritis
- 2011
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The purpose of the present study was to investigate the frequency of the PTPN22 +1858 C/T single nucleotide polymorphism (SNP) (rs 2476601), previously shown to be associated with several autoimmune diseases, in patients with psoriatic arthritis (PsA) in comparison with population based controls.METHODS: A total of 291 patients (145 male/146 female, mean age (± S.D.) 52.2 (± 13.1) years) with PsA were examined clinically, by standard laboratory tests and their DNA was genotyped for the SNP rs2476601 (PTPN22 +1858 C/T). Allelic frequencies were determined and compared with 725 controls.RESULTS: Carriage of the risk allele, PTPN22+1858T, showed a significant association with patients with PsA compared with controls (χ2 = 6.56, P = 0.010, odds ratio (OR) 1.49; 95% confidence interval (CI) 1.10 to 2.02). A significantly higher proportion of carriers of the risk allele (T) had significantly more deformed joints (n ± SEM) (5.9 ± 1.2 vs 2.8 ± 0.5; P = 0.005).CONCLUSIONS: In this study the +1858T allele of the PTPN22 gene, known to be associated with several autoimmune diseases, was associated with PsA. The finding of significantly more joints with deformities among carriers of the T variant could indicate a more aggressive phenotype of disease.
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| 7. |
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| 8. |
- Lindqvist, Ulla, 1948-, et al.
(författare)
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Psoriasisartrit
- 2011. - 2. uppl
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Ingår i: Reumatologi. - Stockholm : Studentlitteratur. - 9789144055329 ; , s. 111-118
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Madsen, Rasmus Kirkegaard, 1979-, et al.
(författare)
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Diagnostic properties of metabolic perturbations in rheumatoid arthritis
- 2011
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:1, s. R19-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of the study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with those of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93 % and a specificity of 70 % in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90 % and a specificity of 94 %. Glyceric acid, D-ribofuranoise and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased when compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was irrespective of the presence of antibodies against cyclic citrullinated peptides (ACPA).
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| 10. |
- Theander, Elke, et al.
(författare)
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Early psoriatic arthritis : short symptom duration, male gender and preserved physical functioning at presentation predict favourable outcome at 5-year follow-up. Results from the Swedish Early Psoriatic Arthritis Register (SwePsA)
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 73:2, s. 407-413
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe Swedish Early Psoriatic Arthritis Register describes the course of early psoriatic arthritis (PsA) in a real life clinical setting in Sweden. The aim of this study was to obtain information on predictors of clinical outcomes over a 5-year period with special focus on effects of gender, joint patterns, diagnostic delay and initial disease activity.MethodsIn six centres, patients with signs suggestive of PsA were included in the Swedish Early Psoriatic Arthritis Register within 2 years of symptom onset. CASPAR (classification for psoriatic arthritis) criteria were fulfilled by 197 patients who had passed the 5-year follow-up. Disease activity was measured by the Disease Activity Score including 28 joints (DAS28) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). Remission and minimal disease activity (MDA) were used as outcome measures.ResultsMean age at inclusion was 46 years, younger in male than female patients (43 vs 48 years). Mean DAS28 was 3.7 and 3.0 at inclusion and 2.8 and 2.1 at follow-up for women and men, respectively-significantly higher in women at both visits. Likewise, DAPSA scores were significantly higher in women. The degree of improvement (change in DAS28 and DAPSA) was similar. Men achieved MDA or remission (50% vs 33%, 25% vs 13%, respectively) more often, and women had significantly more polyarthritis at inclusion (49% vs 27%) and after 5 years (25% vs 15%). Axial or mono/oligoarticular disease was predominant in men. Independent predictors of MDA at the 5-year follow-up were: shorter symptom duration; greater general wellbeing (global visual analogue scale); and low Health Assessment Questionnaire at inclusion.ConclusionsIn early PsA, short delay between onset of symptoms and diagnosis, preserved function, and male gender are the most important predictors of favourable clinical outcome at the 5-year follow-up. Early recognition of PsA and active treatment may be important, particularly in women with polyarticular disease.
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