Clinicopathological features of anti-mitochondrial M2 antibody-positive myositis based on a cohort of 201 patients from Japan

It is still unknown whether anti-mitochondrial M2 antibody (AM2A)-positive myositis is an independent subtype of autoimmune myositis (AIM). The aim of this study is to better characterize the clinicopathological features of AM2A-associated myositis. This study utilized muscle biopsy samples from serologically AM2A-positive patients, which were sent to the National Center of Neurology and Psychiatry for diagnostic purposes from January 2008 to December 2020. We reviewed muscle biopsies and clinical information of 201 patients. The clinicopathologic features of them were compared with the features of 101 patients with immune-mediated necrotizing myopathy (IMNM), 212 with anti-synthetase syndrome or 256 with dermatomyositis using uniform manifold approximation and projection, principal component analysis (PCA) and logistic regression model. AM2A-positive patients had the longest disease duration before muscle biopsy (pre-biopsy disease duration: PBDD), 48.7±63.0 months and the highest frequency of arrhythmia, 51.1%. Necrotic and/or regenerating fibers were seen in 93.5% and membrane attack complex sarcolemmal deposits were noted in 43.3%. Interestingly, patients with shorter PBDD showed more CD8-positive lymphocyte infiltrates and higher serum creatine kinase (CK) levels, whereas longer PBDD was associated with a higher frequency of arrhythmia. PCA separated disease groups with high weight of muscle pathology components on 2D plotting, although AM2A-positive myositis and IMNM were partly overlapped. On logistic regression model analysis, we obtained high sensitivity (0.846) and specificity (0.842) for distinguishing them. We proposed that AM2A-positive myositis is an independent subtype of AIMs characterized by IMNM-like muscle pathology with a high prevalence of cardiac involvement and a chronic disease course; the disease is associated with high CK level and endomysial CD8-positive lymphocyte infiltration in early stages and arrhythmia in later stages. It is still unknown whether anti-mitochondrial M2 antibody (AM2A)-positive myositis is an independent subtype of autoimmune myositis (AIM). The aim of this study is to better characterize the clinicopathological features of AM2A-associated myositis. This study utilized muscle biopsy samples from serologically AM2A-positive patients, which were sent to the National Center of Neurology and Psychiatry for diagnostic purposes from January 2008 to December 2020. We reviewed muscle biopsies and clinical information of 201 patients. The clinicopathologic features of them were compared with the features of 101 patients with immune-mediated necrotizing myopathy (IMNM), 212 with anti-synthetase syndrome or 256 with dermatomyositis using uniform manifold approximation and projection, principal component analysis (PCA) and logistic regression model. AM2A-positive patients had the longest disease duration before muscle biopsy (pre-biopsy disease duration: PBDD), 48.7±63.0 months and the highest frequency of arrhythmia, 51.1%. Necrotic and/or regenerating fibers were seen in 93.5% and membrane attack complex sarcolemmal deposits were noted in 43.3%. Interestingly, patients with shorter PBDD showed more CD8-positive lymphocyte infiltrates and higher serum creatine kinase (CK) levels, whereas longer PBDD was associated with a higher frequency of arrhythmia. PCA separated disease groups with high weight of muscle pathology components on 2D plotting, although AM2A-positive myositis and IMNM were partly overlapped. On logistic regression model analysis, we obtained high sensitivity (0.846) and specificity (0.842) for distinguishing them. We proposed that AM2A-positive myositis is an independent subtype of AIMs characterized by IMNM-like muscle pathology with a high prevalence of cardiac involvement and a chronic disease course; the disease is associated with high CK level and endomysial CD8-positive lymphocyte infiltration in early stages and arrhythmia in later stages.