Antimelanoma differentiation-associated protein 5 antibody level is a novel tool for monitoring disease activity in rapidly progressive interstitial lung disease with dermatomyositis.

Antimelanoma differentiation-associated protein (anti-MDA)5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. Twelve patients with CADM (n = 10) or DM (n = 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded. Serial measurements of anti-MDA5 antibody levels were measured. All patients were treated with corticosteroids, tacrolimus and intravenous cyclophosphamide. All patients achieved RP-ILD remission after combined immunosuppressive therapy for a mean of 6·8 months, with significant decreases noted in the mean anti-MDA5 antibody levels at remission. Six (50%) patients became anti-MDA5 antibody negative after therapy. After a mean follow-up of 31 months, RP-ILD relapse was observed in four (33%) patients in both the anti-MDA5 antibody sustained positive group and the negative conversion group. However, relapsed patients in the sustained positive group relapsed earlier than those in the negative conversion group. Thus, a decrease in anti-MDA5 antibody levels during remission was associated with longer remission. Relapses were associated with a reincrease of anti-MDA5 antibody levels in four of four (100%) patients. In contrast, none of the patients without reincrease in anti-MDA5 antibody exhibited symptoms of relapse during follow-up. Therefore, reincrease in anti-MDA5 antibody levels was associated with relapse. The anti-MDA5 antibody level is a novel parameter for monitoring and a good predictor of RP-ILD relapse in patients with CADM or DM.

Matsushita T ，Mizumaki K ，Kano M ，Yagi N ，Tennichi M ，Takeuchi A ，Okamoto Y ，Hamaguchi Y ，Murakami A ，Hasegawa M ，Kuwana M ，Fujimoto M ，Takehara K ... -  《-》

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 ... -  《-》

Recurrence of anti-MDA5 antibody-positive clinically amyopathic dermatomyositis after long-term remission: A case report.

Endo Y ，Koga T ，Ishida M ，Fujita Y ，Tsuji S ，Takatani A ，Shimizu T ，Sumiyoshi R ，Igawa T ，Umeda M ，Fukui S ，Nishino A ，Kawashiri SY ，Iwamoto N ，Ichinose K ，Tamai M ，Nakamura H ，Origuchi T ，Kuwana M ，Hosono Y ，Mimori T ，Kawakami A ... -  《-》

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 ... -  《-》

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 ... -  《-》