HRCT features of interstitial lung disease in dermatomyositis with anti-CADM-140 antibody.

Anti-CADM-140 antibody (anti-CADM-140), also referred to as anti-melanoma differentiation-associated gene 5 (MDA5) antibody, is a myositis-specific antibody identified in the sera of patients with clinically amyopathic dermatomyositis (C-ADM) and is associated with a worse prognosis in dermatomyositis-associated interstitial lung disease (DM-ILD). We sought to determine high-resolution computed tomography (HRCT) features of DM-ILD with anti-CADM-140. Twenty-five patients newly diagnosed with DM-ILD at Kyoto University Hospital between 2005 and 2009 were retrospectively reviewed. Serum anti-CADM-140 was measured in all patients at their first visit. Chest HRCT images taken prior to treatment were classified based on the dominant findings and their distribution, and compared between patients with and without the antibody. Of 25 DM-ILD patients, 12 were positive and 13 were negative for anti-CADM-140. HRCT patterns differed significantly between anti-CADM-140-positive and negative patients (P = 0.002). Lower consolidation or ground-glass attenuation (GGA) pattern (50.0%) and random GGA pattern (33.3%) were the predominant patterns in anti-CADM-140-positive cases, while lower reticulation pattern (69.2%) was frequently seen in anti-CADM-140-negative cases. Anti-CADM-140-positive cases were also significantly characterized by the absence of intralobular reticular opacities (0% in anti-CADM-140 (+) vs. 84.6% in anti-CADM-140 (-), P < 0.0001). Anti-CADM-140-positive DM-ILD was characterized by lower consolidation or GGA pattern, random GGA pattern, and the absence of intralobular reticular opacities.

Tanizawa K ，Handa T ，Nakashima R ，Kubo T ，Hosono Y ，Watanabe K ，Aihara K ，Oga T ，Chin K ，Nagai S ，Mimori T ，Mishima M ... -  《-》

The prognostic value of HRCT in myositis-associated interstitial lung disease.

Polymyositis and dermatomyositis-associated interstitial lung disease (PM/DM-ILD) can have variable courses. We evaluated the prognostic value of high-resolution computed tomography (HRCT) in PM/DM-ILD. The cases of 51 patients newly diagnosed with PM/DM-ILD were retrospectively reviewed. HRCT images at diagnosis were categorized into four radiological patterns based on the major findings and distributions of these abnormalities, and the disease extent on HRCT was scored. The impact of HRCT findings and other clinical parameters on day 90 and overall mortality were analyzed. Of the 51 patients (11 with polymyositis and 40 with dermatomyositis), the lower consolidation/ground-glass attenuation (GGA) pattern was observed in 21 patients (41%), lower reticulation was observed in 23 patients (45%), random GGA was observed in four patients (8%), and other patterns were observed in three patients (6%). Twenty-one patients (42%) were positive for anti-CADM-140. The lower consolidation/GGA pattern, clinically amyopathic dermatomyositis, fever (≥38.0 °C), ferritin levels >500 ng/mL, and the presence of anti-CADM-140 were significantly associated with 90-day mortality in univariate analysis. Multivariate analysis revealed that the lower consolidation/GGA pattern (odds ratio, 23.1; P = 0.02) and the presence of anti-CADM-140 (odds ratio, 14.1; P = 0.03) were independent predictors of 90-day mortality. This HRCT pattern was also associated with a higher 90-day morality rate among anti-CADM-140-positive patients. The lower consolidation/GGA pattern was also associated with overall mortality in univariate analysis, whereas only the presence of anti-CADM-140 was an independent determinant of overall mortality in multivariate analysis. HRCT patterns at diagnosis can help predict the prognosis of patients with PM/DM-ILD as well as the presence of anti-CADM-140.

Tanizawa K ，Handa T ，Nakashima R ，Kubo T ，Hosono Y ，Aihara K ，Ikezoe K ，Watanabe K ，Taguchi Y ，Hatta K ，Oga T ，Chin K ，Nagai S ，Mimori T ，Mishima M ... -  《-》

Serum cytokine profiles of patients with interstitial lung disease associated with anti-CADM-140/MDA5 antibody positive amyopathic dermatomyositis.

Patients with amyopathic dermatomyositis (ADM) sometimes develop rapidly progressive interstitial lung disease (ILD) predominantly in Asia. Although anti-CADM-140/MDA5 antibody titer could correlate with disease activity and predict the course of ILD associated with ADM, it is not clear how this antibody is involved in the pathogenesis of ILD in ADM. We retrospectively collected clinical records and preserved serum before treatment of consecutive patients with ADM-ILD treated in the Niigata University Medical and Dental Hospital since 2000. We measured anti-CADM-140/MDA5 antibody titer and compared it between survivors and non-survivors. Serum cytokine/growth factor protein concentration was measured using a multiplex immunoassay system. The associations between anti-CADM-140/MDA5 antibody titer and each cytokine/growth factor protein concentration were evaluated. Thirteen patients were enrolled into the study. Among them, four patients did not respond to intensive immunosuppressive therapy and died. The mean anti-CADM-140/MDA5 antibody titer was significantly higher in patients who did not responded to therapy than in those who survived (p < 0.05). Relationship analyses between the antibody titer and each cytokine/GF protein concentration revealed that Spearman's rank correlation coefficients were more than 0.4 in thirteen cytokine/GF proteins. In particular, the strongest correlation was found between anti-CADM-140/MDA5 antibody titer and CX3CL1 (r = 0.8897). These results confirmed that anti-CADM-140/MDA5 antibody levels could predict outcomes of ADM-ILD. Relationship analyses suggested that CX3CL1 might be involved in the pathogenesis of anti-CADM-140/MDA5 antibody positive ADM-ILD.

Takada T ，Aoki A ，Asakawa K ，Sakagami T ，Moriyama H ，Narita I ，Sato S ... -  《-》

Differential clinical features of patients with clinically amyopathic dermatomyositis who have circulating anti-MDA5 autoantibodies with or without myositis-associated autoantibodies.

Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies have been identified as myositis-specific autoantibodies that are often associated with clinically amyopathic dermatomyositis (CADM) and a poor prognosis due to rapidly progressive interstitial lung disease (RP-ILD) in East Asian patients. Besides anti-MDA5 autoantibodies, patients with CADM may have myositis-associated autoantibodies (MAAs), which characterize other connective tissue diseases such as rheumatoid arthritis and Sjögren's syndrome. However, the clinical significance of the coexistence of anti-MDA5 autoantibodies and MAAs in patients with CADM remains unclear. We retrospectively analyzed 24 patients with CADM who had anti-MDA5 autoantibodies. Their clinical phenotypes including laboratory test results, high-resolution lung computed tomography data, response to therapy, and prognosis were compared between those who were positive and negative for MAAs, such as antinuclear antibody (ANA), anti-cyclic citrullinated peptide (CCP), anti-SSA, and anti-SSB antibodies. Among 24 patients, 9 (37.5%) additionally had at least one of the MAAs examined in this study: 1 patient was positive for ANA, 5 for anti-CCP, 5 for either anti-SSA or anti-SSB, 1 for anti-cardiolipin, and 1 for anti-Scl-70. Although all anti-MDA5-positive patients with CADM had ILD, the MAA-positive patients showed a lower risk of developing RP-ILD (p = 0.03), a more favorable response to combination therapy of corticosteroids and immunosuppressive agents, and a lower mortality rate than patients with no MAAs (p = 0.03). Our data suggest that anti-MDA5-positive patients with CADM who also have MAAs have a better prognosis than those without MAAs; thus, anti-MDA5 autoantibodies by themselves may not be strong predictors of worse clinical outcomes in patients with CADM. Coexistent MAAs could be biomarkers for a favorable prognosis in anti-MDA5-positive patients with CADM.

Yamaguchi K ，Yamaguchi A ，Kashiwagi C ，Sawada Y ，Taguchi K ，Umetsu K ，Oshima K ，Uchida M ，Suzuki M ，Kono S ，Takemura M ，Masubuchi H ，Kitahara S ，Hara K ，Maeno T ，Motegi SI ，Muro Y ，Sakairi T ，Hisada T ，Kurabayashi M ... -  《-》

Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody-positive Dermatomyositis-associated Interstitial Lung Disease.

Fujisawa T ，Hozumi H ，Yasui H ，Suzuki Y ，Karayama M ，Furuhashi K ，Enomoto N ，Nakamura Y ，Inui N ，Suda T ... -  《-》