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 ... -  《-》

Prognostic values of anti-Ro52 antibodies in anti-MDA5-positive clinically amyopathic dermatomyositis associated with interstitial lung disease.

Anti-Ro52 antibody often co-occurs with anti-Jo1 antibody in antisynthetase syndrome and their co-occurrence correlates with a more aggressive clinical phenotype and poorer prognosis. The strong association of anti-Ro52 antibody with anti-melanoma differentiation-associated protein-5 (anti-MDA5) antibody has been indicated in juvenile myositis. The aim of this study was to assess the clinical significance of anti-Ro52 antibody in a cohort of adult patients with anti-MDA5-positive clinically amyopathic dermatomyositis with interstitial lung disease (CADM-ILD). We assessed a cohort of 83 consecutive patients with anti-MDA5-positive CADM-ILD. Anti-MDA5 antibodies and anti-Ro52 antibodies were detected in immunoblotting and semi-quantitatively analysed by densitometry. Clinical features and the 24 month survival were compared between anti-MDA5-positive patients with and without anti-Ro52 antibodies. Anti-Ro52 antibodies were found in 74.7% of anti-MDA5-positive CADM-ILD patients and were associated with an increased frequency of rapidly progressive interstitial lung disease (RP-ILD; 54.8% vs 23.8%; P = 0.014) and cutaneous ulcerations (27.4% vs 4.8%; P = 0.033). The cumulative 24 month survival rate tended to be lower in patients with anti-Ro52 antibodies than patients without (59.9% vs 85.7%; P = 0.051). The combination of anti-Ro52 antibody status and anti-MDA5 antibody levels further stratified patients' survival rates, showing that the survival rate of patients who were dual positive for anti-MDA5 antibody and anti-Ro52 antibody was significantly lower than patients with mild positive anti-MDA5 antibody alone (59.9% vs 100%; P = 0.019). Anti-Ro52 antibody is highly prevalent in anti-MDA5-positive CADM-ILD patients and their coexistence correlates with a subgroup of patients with more aggressive phenotypes. The combination of anti-MDA5 antibody levels and anti-Ro52 antibody status could help to predict patients' prognosis and guide risk-based therapy.

Xu A ，Ye Y ，Fu Q ，Lian X ，Chen S ，Guo Q ，Lu LJ ，Dai M ，Lv X ，Bao C ... -  《-》

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 ... -  《-》

Clinical Features of Anti-MDA5 Antibody-positive Rapidly Progressive Interstitial Lung Disease without Signs of Dermatomyositis.

Sakamoto N ，Ishimoto H ，Nakashima S ，Yura H ，Miyamura T ，Okuno D ，Hara A ，Kitazaki T ，Kakugawa T ，Ishimatsu Y ，Satoh M ，Mukae H ... -  《-》

A case of anti-MDA5-positive rapidly progressive interstitial lung disease in a patient with clinically amyopathic dermatomyositis ameliorated by rituximab, in addition to standard immunosuppressive treatment.

Koichi Y ，Aya Y ，Megumi U ，Shunichi K ，Masafumi S ，Hiroaki M ，Masahiko K ，Shinsuke K ，Manabu U ，Kenichiro H ，Fumiaki A ，Nozomi A ，Toshitaka M ，Masayoshi Y ，Chikako K ，Yoshinao M ，Tatsuo S ，Masahiko K ... -  《-》