Effects of bile salt-stimulated lipase on blood cells and associations with disease activity in human inflammatory joint disorders.

The bile salt-stimulated lipase (BSSL) was originally recognized as a lipolytic enzyme expressed by the exocrine pancreas and in some species, notably humans, the lactating mammary gland, being secreted into the duodenum and with the mother's milk, respectively. However, BSSL is also present in the blood and has been assigned additional functions, even beyond the gastrointestinal tract. Conventional BSSL knockout mice are protected from developing disease in animal models of arthritis, and antibodies directed towards BSSL prevent or mitigate disease in similar models. The aim of this study was to investigate the role of BSSL as a newly discovered player in inflammation and specifically in inflammatory joint disorders. As part of mechanism of action, we here show that BSSL is secreted by neutrophils, interacts with monocytes and stimulates their migration in vitro. An anti-BSSL antibody that blocks the human BSSL-monocyte interaction was shown to simultaneously prevent the signaling pathway by which BSSL induce cell migration. Moreover, in this cohort study we show that BSSL levels are significantly higher in blood samples from patients with rheumatoid arthritis and psoriatic arthritis compared to healthy controls. The BSSL levels in patients' blood also correlated with disease activity scores and established inflammatory markers. Hence, although the mode of action is not yet fully clarified, we conclude that BSSL could be considered a proinflammatory component in the innate immune system and thus a possible novel target for treatment of chronic inflammation.

Methotrexate treatment in early psoriatic arthritis in comparison to rheumatoid arthritis: an observational nationwide study.

INTRODUCTION: We aimed to compare the proportions of patients with newly diagnosed psoriatic arthritis (PsA) and rheumatoid arthritis (RA) remaining on methotrexate (regardless of other disease-modifying antirheumatic drug (DMARD)-changes), and proportions not having started another DMARD (regardless of methotrexate discontinuation), within 2 years of starting methotrexate, as well as methotrexate effectiveness. METHODS: Patients with DMARD-naïve, newly diagnosed PsA, starting methotrexate 2011-2019, were identified from high-quality national Swedish registers and matched 1:1 to comparable patients with RA. Proportions remaining on methotrexate and not starting another DMARD were calculated. For patients with disease activity data at baseline and 6 months, response to methotrexate monotherapy was compared through logistic regression, applying non-responder imputation. RESULTS: In total, 3642/3642 patients with PsA/RA were included. Baseline patient-reported pain and global health were similar, whereas patients with RA had higher 28-joint scores and evaluator-assessed disease activity. Two years after methotrexate start, 71% of PsA vs 76% of patients with RA remained on methotrexate, 66% vs 60% had not started any other DMARD, and 77% vs 74% had not started specifically a biological or targeted synthetic DMARD. At 6 months, the proportions of patients with PsA versus RA achieving pain-scores ≤15 mm were 26% vs 36%; global health ≤20 mm: 32% vs 42%; evaluator-assessed 'remission': 20% vs 27%, with corresponding adjusted ORs (PsA vs RA) of 0.63 (95% CI 0.47 to 0.85); 0.57 (95% CI 0.42 to 0.76) and 0.54 (95% CI 0.39 to 0.75). DISCUSSION: In Swedish clinical practice, methotrexate use is similar in PsA and RA, both regarding initiation of other DMARDs and methotrexate retention. On a group level, disease activity improved during methotrexate monotherapy in both diseases, although more so in RA.

Hormonal and Reproductive Factors in Relation to Cardiovascular Events in Women with Early Rheumatoid Arthritis.

Hormonal and reproductive factors affect the risk for cardiovascular events (CVE) in the general population. Although the risk of CVE is increased in rheumatoid arthritis (RA), the knowledge about the impact of hormonal factors for CVE in RA is sparse. Female postmenopausal patients ≤80 years with early RA were consecutively included in this observational study (n = 803) between 1 January 1996 until 31 December 2017. Questionnaires regarding hormonal factors were distributed from the index date. Data regarding CVE were obtained from the Swedish National Health Register and Cause of Death Register. Associations between CVE and hormonal factors were analyzed using Cox proportional hazard regression. Of the postmenopausal women, 64 women had a CVE after RA onset. The time period from menopause to RA onset was significantly longer for CVE cases with higher proportion of postmenopausal women. In Cox proportional hazard regression models, years from last childbirth and multiparity were associated with higher CVE risk. Adjustments for traditional risk factors did not affect the results except for hypertension. RA onset after menopause and a longer duration from menopause until onset increased the CVE risk. Multiparity was associated with higher CVE risk whilst oral contraceptives decreased the risk. These results can contribute to identification of high-risk patients for CVE beyond traditional risk factors.

Health-related quality of life in early psoriatic arthritis compared with early rheumatoid arthritis and a general population.

OBJECTIVE: Both psoriatic arthritis (PsA) and rheumatoid arthritis (RA) have a significant impact on quality of life, but few reports have compared the two diseases. The current study assessed health-related quality of life (HRQoL) in PsA at diagnosis and after five years compared with early rheumatoid arthritis (RA) and a matched general population. METHODS: Patients with early PsA and early RA included in two Swedish registries with HRQoL data measured by the Medical Outcomes Study Short Form 36 (SF-36) at baseline and at five years follow-up were included. Differences in SF-36 scores compared with the general population were calculated for each patient. Physical function, disease activity, the delay before diagnosis, pain, and general wellbeing were used as explanatory variables. Statistical tests included t-tests and univariate and multivariate linear regression. RESULTS: PsA (n = 166) and RA (n = 133) patients of both sexes had significantly reduced HRQoL at disease onset. After five years, PsA patients still had impairments in several domains of SF-36, whereas RA patients had an almost normalized HRQoL. The time from symptom onset to diagnosis, disease activity, and disability independently contributed to the reduced improvement in PsA. CONCLUSION: Both early PsA and RA are characterized by severely reduced HRQoL. Despite more severe disease at inclusion, normalization of HRQoL is seen in patients with RA but not PsA. This may be due to delay in the diagnosis of PsA or more powerful interventions in RA. Earlier detection, lifestyle intervention, and more aggressive management strategies may be needed for PsA.

Mosquitoborne Sindbis Virus Infection and Long-Term Illness.

An unexpected human outbreak of the mosquitoborne Sindbis virus occurred in a previously nonendemic area of Sweden. At follow-up, 6-8 months after infection, 39% of patients had chronic arthralgia that affected their daily activities. Vectorborne infections may disseminate rapidly into new areas and cause acute and chronic disease.

DAPSA, DAS28 and MDA predict long-term treatment regime in psoriatic arthritis. The Swedish Early Psoriatic Arthritis Cohort.

OBJECTIVES: To describe treatment patterns in the Swedish early psoriatic arthritis cohort (SwePsA) of the mono-/oligo-arthritic (M/O) and polyarthritis (P) and identify early predictive factors for treatment with disease-modifying anti-rheumatic (DMARD), non-steroidal anti-inflammatory drugs (NSAID), and tumour necrosis factor inhibition (TNFi) after 5 years. METHODS: Data for 198 M/O and P PsA were obtained within the programme for SwePsA. Multinomial and binary logistic regression analyses were used to assess the association between early predictive factors and treatment after 5 years adjusted for age at inclusion. The analysis of DMARD/NSAID was adjusted for medication at inclusion. RESULTS: After inclusion visit, DMARD was prescribed in 30% of M/O and 56% of P PsA; mainly methotrexate. TNFi was not prescribed at inclusion, but 23 patients were treated at 5-year follow-up. The adjusted OR (95% CI) for treatment with both DMARD and NSAID after 5 years was 3.65 (1.34 - 9.89) (p=0.010) for Disease Activity Score 28 (DAS28) >3.2 and 2.90 (1.20-6.99) (p=0.038) for Disease Activity Index in Psoriatic Arthritis (DAPSA) >14 at inclusion. TNFi treatment was, after adjusting for age, associated with high erythrocyte sedimentation rate (p=0.0043), high C-reactive protein (p=0.013), DAPSA (p<0.001), not reaching minimal disease activity (p=0.001) high health assessment questionnaire (p=0.001), patient's overall assessment on the visual analogue scale (VAS) (p=0.009), high pain VAS (p=0.007), and high number of tender and swollen joints (p=0.031) at inclusion. CONCLUSIONS: Disease activity in early M/O and P PsA is to be considered in deciding the level of health care assessment and future pharmacological treatment. DAS28 >3.2 and DAPSA>14 early in the disease predict subsequent treatment with DMARD. For prediction of biological treatment, not reaching MDA at onset of disease, would be the composite index of choice.

Disease Activity and Increased Risk of Cardiovascular Death among Patients with Psoriatic Arthritis.

OBJECTIVE: Recent studies indicate increased cardiovascular (CV) morbidity and mortality in patients with psoriatic arthritis (PsA), but results are inconsistent. This prompted our investigation of the mortality rate, cause of death, and incidence of acute CV events in patients from northern Sweden with PsA. METHODS: Patients with established PsA (464) were included. To calculate standardized mortality ratio (SMR) and standardized incidence ratio (SIR) for CV events, data were extracted from the National Causes of Death Register and the National Inpatient Care Register in Sweden, and compared with the general population. The study period was 1995-2011. To study the effect of inflammatory activity, a composite disease activity index (DAI) was used. RESULTS: The SMR (95% CI) for overall mortality and diseases of the circulatory system (International Classification of Diseases, 10th edition; I00-I99) was 1.22 (0.89-1.63) and 1.64 (1.02-2.52), respectively. In regression analysis, DAI was significantly associated with death (OR 1.99, 95% CI 1.41-2.80) when adjusted for age and sex (p < 0.001), and remained significant after stratifying patients into the 2 major causes of death: diseases of the circulatory system and malignant neoplasms. Peripheral and axial disease was associated with death (OR 4.02, 95% CI 1.84-8.84, p < 0.001) compared with peripheral disease only. The SIR (95% CI) for a CV event (myocardial infarction or stroke) was 0.597 (0.40-0.86); this association was only significant in men. CONCLUSION: Patients with PsA had a small but significant increase in SMR for death due to diseases of the circulatory system compared with the general population. Among patients, death was associated with DAI, as well as axial involvement in combination with peripheral disease, indicating more aggressive disease phenotypes.

The Swedish Early Psoriatic Arthritis Registry 5-year Followup: Substantial Radiographic Progression Mainly in Men with High Disease Activity and Development of Dactylitis.

OBJECTIVE: To describe early radiographic findings in patients from the Swedish psoriatic arthritis (SwePsA) registry, progression of destruction, correlations with clinical disease variables, and predictors of destruction. METHODS: Hand and foot radiographs were available for 72 of 197 SwePsA patients followed for 5 years. Clinical data were collected according to the SwePsA protocol. RESULTS: Disease characteristics and clinical improvement were similar in men and women. Radiographic abnormalities were more pronounced in men. Total Wassenberg radiographic score at baseline was 0 in 45% of men and 51% of women. One man and one woman had a score > 10. At 5 years, total score was 0 in 14% of men and 40% of women (p = 0.018); 17% of men and 7% of women had scores > 10. Mean total scores for men and women had increased. Baseline erythrocyte sedimentation rate was associated with baseline total radiographic score. In men, swollen joint count was positively, and in women tender joint count negatively, correlated to total radiographic score. After 5 years, only male scores, mainly hand scores, significantly correlated with 28-joint Disease Activity Score and Disease Activity Index for Psoriatic Arthritis scores, swollen joint count, and dactylitis. Achieving remission or minimal disease activity after 5 years protected against structural damage, mainly in men. CONCLUSION: Radiographic progression in early PsA was generally slow but substantial. Male sex appears to be a risk factor for early radiographic damage while the presence of baseline radiographic damage and dactylitis developing during followup seem to predict further destruction. Hand and foot radiograph scoring cannot be substituted with clinical signs.

PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus.

OBJECTIVES: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA. METHODS: A total of 15 single nucleotide polymorphisms were selected (PImmunochip <1×10(-4)) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity. RESULTS: We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49×10(-9), OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2×10(-4)). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27×10(-9)). CONCLUSIONS: For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis.

Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8(+) memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.

S-calprotectin (S100A8/S100A9): a potential marker of inflammation in patients with psoriatic arthritis.

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; rs=0.441), swollen joint count (P=0.002, rs=0.397), and CXCL10 (P=0.046, rs=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 than mono-/oligoarthritis. S-calprotectin is considered a potential marker of disease activity in patients with PsA.

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).

OBJECTIVE: The 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. METHODS: In 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. RESULTS: Mean 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 well-being (global visual analogue scale); and low Health Assessment Questionnaire at inclusion. CONCLUSIONS: In 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.

Variants in RUNX3 contribute to susceptibility to psoriatic arthritis, exhibiting further common ground with ankylosing spondylitis.

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 × 10(-8) by Cochran-Mantel-Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.15-1.33). 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 × 10(-2) ; OR 1.13 [95% CI 1.00-1.28]), 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 cell-mediated diseases.

Association between the PTPN22 +1858 C/T polymorphism and psoriatic arthritis.

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.

Diagnostic properties of metabolic perturbations in rheumatoid arthritis.

INTRODUCTION: The aim of this 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 that 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-ribofuranose and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was without regard to the presence of antibodies against cyclic citrullinated peptides.

Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis.

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 × 10⁻²°, 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.

The Swedish early psoriatic arthritis register-- 2-year followup: a comparison with early rheumatoid arthritis.

OBJECTIVE: Patients with symptoms and signs compatible with psoriatic arthritis (PsA), with or without psoriasis, have been documented in the Swedish Early Psoriatic Arthritis (SwePsA) register. Our aim was to find markers for disease progression and to evaluate treatments for PsA using these data. METHODS: Patients referred to rheumatology outpatient clinics within 2 years of onset were assessed on inclusion and at followup 2 years later. Data collection was performed according to the program for SwePsA, and classification was as described by Moll and Wright and the ClASsification Criteria for Psoriatic ARthritis (CASPAR). Remission was recorded if the patient had no tender or swollen joints and if erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were within the reference range. Patients with early rheumatoid arthritis (RA) recruited from the Swedish Early Rheumatoid Arthritis Register (Ramona) provided comparison data. RESULTS: One hundred thirty-five patients with PsA according to CASPAR were assessed; 44% were classified as having mono/oligoarthritis and 47% as polyarthritis. Two patients (1%) were in remission initially, and 23 (17%) at followup. Patients with polyarticular disease had the highest inflammatory activity, measured by swollen and tender joint counts, ESR, Health Assessment Questionnaire, and self-assessment by visual analog scale of pain and global disease activity. Dactylitis was associated with radiological findings. Compared with RA patients, they had significantly lower CRP, ESR, and number of swollen joints (p = 0.0003, p = 0.0026, p = 0.0380, respectively) at inclusion, but equal numbers of tender joints and self-assessment of pain and disease activity. CONCLUSION: About half the patients had polyarthritis and the other half had mono/oligoarthritis at followup after 2 years. Patients with polyarthritis had the highest inflammatory activity. Apart from ESR, CRP, and swollen joint count, there were no significant differences in activity between RA and polyarticular PsA.

Analysis of 6 genetic loci for disease susceptibility in psoriatic arthritis.

OBJECTIVE: To analyze the association of several autoimmune disease susceptibility loci in a population of patients with psoriasis and defined joint disease from northern Sweden. METHOD: One hundred twenty patients with psoriasis and defined joint disease were examined clinically, radiologically, and with laboratory-based analyses. Disease classification was based on peripheral and/or axial engagement. The tumor necrosis factor (TNF) locus, 1q21 (PSORS4), 3q21 (PSORS5), 8q24, 16q21, and the CTLA4 gene were analyzed using a total of 38 microsatellite markers and 2 single nucleotide polymorphisms (SNP). Ninety-four controls with the same ethnic background as the patients were randomly selected from the same region of Sweden. RESULTS: An association was found with one of the markers in the TNFB locus within the HLA region (p = 0.012, pc = 0.024). Three markers at the PSORS4 locus on chromosome 1q21 and 2 markers at the 8q24 locus showed nominal p values of < 0.05. After applying the Bonferroni correction for multiple analyses these markers did not reach significance. No other marker showed significant association. In a subgroup of the patients, possible linkage disequilibrium between the TNFB123 and HLA-B antigens, B17, B27, B37, B44, and B62 was analyzed. A significant linkage (p = 0.0001) was found. CONCLUSION: We identified an association between psoriatic arthritis and one of the microsatellite markers within the TNFB locus at the HLA region on chromosome 6. Linkage disequilibrium between TNFB123 and certain HLA-B antigens was found.

Inflammatory joint manifestations are prevalent in psoriasis: prevalence study of joint and axial involvement in psoriatic patients, and evaluation of a psoriatic and arthritic questionnaire.

OBJECTIVE: To examine the prevalence of inflammatory manifestations, such as peripheral arthritis, axial disease, undifferentiated spondyloarthropathy (uSpA) and enthesopathies in patients with psoriasis, and to evaluate a psoriatic and arthritic questionnaire (PAQ) to identify patients with arthritis. Methods. An evaluation of a questionnaire (PAQ) in a hospital- and community-based population of 276 psoriatic patients, and clinical, radiological, and laboratory examination of the 202 patients answering the questionnaire and willing to participate in the subsequent study. Results. Ninety-seven patients (48%) were identified as having, or having had, inflammatory manifestations (peripheral arthritis, axial disease, uSpA, and enthesopathies). Sixty-seven patients (33%) had peripheral arthritis and/or axial disease, 30 of whom had not previously been diagnosed. A total PAQ score of 4 out of 8 was the best cutoff value detecting arthritis with a sensitivity of 60% and a specificity of 62.2%. A positive answer to the question "Have you ever thought you might have arthritis?" in combination with morning stiffness in peripheral joints for at least 60 min, had a sensitivity of 30% and a specificity of 91.1% and was significantly associated with peripheral arthritis and/or axial disease in multiple logistic regression analysis. Conclusion. We found a high prevalence of inflammatory joint/axial disease in this group of psoriatic patients. Almost half the patients with peripheral arthritis and/or axial disease had not previously been diagnosed. The PAQ did not, either as a total score or by combining questions, discriminate for arthritis in this population with psoriasis.