Suppressor of TCR signaling-2 (STS-2) suppresses arthritis development in mice

<p><b>Objectives:</b> Suppressor of TCR signaling-2 (STS-2) is one of the RA susceptibility genes identified in genome-wide association studies (GWAS). We tried to verify the involvement of STS-2 on the development of autoimmune arthritis in a mouse model.</p> <p><b>Methods:</b> STS-2 knock-out (KO) and wild type (WT) mice were immunized with chicken type II collagen (CII). For CD4⁺ helper T cell (Th) subset analysis, intracellular cytokines in splenocytes and lymph node cells were stained and analyzed by flow cytometry. Regulatory T cell (Treg) function was analyzed by co-culturing effector CD4⁺T cells and Tregs collected from non-immunized mice.</p> <p><b>Results:</b> CII-immunized STS-2 KO mice developed arthritis more frequently than WT mice. Although the T cell activation profile and Th subset in spleen and LNs were similar between STS-2 KO and WT mice, STS-2 KO mice showed increased IL-2-producing CD4⁺T cells in spleen when compared with WT mice. Accordingly, STS-2 KO CD4⁺T cells promoted IL-2 production by TCR stimulation. However, STS-2 KO Tregs normally suppressed T cell proliferation.</p> <p><b>Conclusion:</b> We proved that STS-2 is involved in the arthritis development by collagen-induced arthritis. Higher IL-2 production from STS-2 KO T cells is suggested to have a main pathogenic role in arthritis development.</p

Prognostic Significance of Anti-Aminoacyl-tRNA Synthetase Antibodies in Polymyositis/Dermatomyositis-Associated Interstitial Lung Disease: A Retrospective Case Control Study

<div><p>Background</p><p>In polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established.</p><p>Objective</p><p>We aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients.</p><p>Methods</p><p>Forty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group).</p><p>Results</p><p>Anti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, <i>P</i> = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, <i>P</i> = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08–0.80; <i>P</i> = 0.01).</p><p>Conclusions</p><p>The presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD.</p></div

Treatment and outcome.

<p>Data are presented as n (%), median (range).</p><p>*<i>P</i> < 0.05</p><p>Treatment and outcome.</p

Univariate Cox hazards analysis for survival.

<p>*<i>P</i> < 0.05</p><p>HR, hazard ratio; 95%CI, 95% confidence interval; ILD, interstitial lung disease; PM, polymyositis; DM, dermatomyositis; CADM, clinically amyopathic dermatomyositis; PaO₂, arterial oxygen pressure; %FVC, predicted forced vital capacity.</p><p>Univariate Cox hazards analysis for survival.</p

Inverse Association between Air Pressure and Rheumatoid Arthritis Synovitis

<div><p>Rheumatoid arthritis (RA) is a bone destructive autoimmune disease. Many patients with RA recognize fluctuations of their joint synovitis according to changes of air pressure, but the correlations between them have never been addressed in large-scale association studies. To address this point we recruited large-scale assessments of RA activity in a Japanese population, and performed an association analysis. Here, a total of 23,064 assessments of RA activity from 2,131 patients were obtained from the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Detailed correlations between air pressure and joint swelling or tenderness were analyzed separately for each of the 326 patients with more than 20 assessments to regulate intra-patient correlations. Association studies were also performed for seven consecutive days to identify the strongest correlations. Standardized multiple linear regression analysis was performed to evaluate independent influences from other meteorological factors. As a result, components of composite measures for RA disease activity revealed suggestive negative associations with air pressure. The 326 patients displayed significant negative mean correlations between air pressure and swellings or the sum of swellings and tenderness (p = 0.00068 and 0.00011, respectively). Among the seven consecutive days, the most significant mean negative correlations were observed for air pressure three days before evaluations of RA synovitis (p = 1.7×10⁻⁷, 0.00027, and 8.3×10⁻⁸, for swellings, tenderness and the sum of them, respectively). Standardized multiple linear regression analysis revealed these associations were independent from humidity and temperature. Our findings suggest that air pressure is inversely associated with synovitis in patients with RA.</p></div

Time course, in each disease, of same-finger <i>C</i> values for images compared with those first acquired data in June.

<p>August DM/PM data could not be acquired because of the absence of patients. Mean values are plotted. ** p<0.01, *** p<0.001.</p

HRCT distributions, findings, and patterns.

<p>Data are presented as n (%), median (range).</p><p>Interobserver agreement on HRCT distributions, findings, and patterns between both radiologists was fair to good (κ = 0.37–0.79).</p><p>*<i>P</i> < 0.05</p><p>HRCT, high-resolution computed tomography; SCLL, subpleural curve linear line; UIP, usual interstitial pneumonia; NSIP, nonspecific interstitial pneumonia; OP, organizing pneumonia.</p><p>HRCT distributions, findings, and patterns.</p

Time course of same-finger <i>C</i> values for images compared with those first acquired in June.

<p>Mean values plus/minus one standard deviation are plotted. *** p<0.001.</p

Patient characteristics.

<p>Data are presented as n (%), median (range).</p><p>*<i>P</i> < 0.05</p><p>ILD, interstitial lung disease; IIM, Idiopathic inflammatory myopathy; PM, polymyositis; DM, dermatomyositis; CADM, clinically amyopathic dermatomyositis.</p><p>Patient characteristics.</p

Number of patients included in this study and disease classification.

<p>Of 56 patients identified, 8 patients were excluded because of comorbid connective tissue diseases (CTDs) (5 patients with Sjögren’s syndrome, 1 with systemic sclerosis, 1 with rheumatoid arthritis, and 1 with systemic lupus erythematosus). There were no patients who had active malignancies at initial diagnosis. Finally, 48 PM/DM-ILD patients were included in this study. PM, polymyositis; DM, dermatomyositis; ILD, interstitial lung disease; CTD, connective tissue disease; SS, Sjögren syndrome; SSc, systemic sclerosis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; ELISA, enzyme-linked immunosorbent assay; RNA-IP, RNA immunoprecipitation.</p