Anti-mitochondrial M2 antibody-positive myositis may be an independent subtype of autoimmune myositis.

It is still unknown whether anti-mitochondrial M2 antibody (AM2A)-positive myositis is an independent subtype of autoimmune myositis (AIM). As such, the aim of this study is to better characterize the clinicopathological features in a large cohort of patients. This study utilized the muscle biopsy samples from AM2A-positive patients, which were sent to the National Center of Neurology and Psychiatry for diagnostic purposes from January 2008 to December 2020. The clinicopathologic information of 201 patients were compared with those who were diagnosed with immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome, or dermatomyositis. AM2A-positive patients had the longest pre-biopsy disease duration (PBDD) at 48.7 ± 63.0 months and the highest frequency of arrhythmia of 51.1%. Necrotic and/or regenerating fibers were seen in 93.5% and membrane attack complex sarcolemmal deposits were noted in 43.3%, similar to IMNM. Furthermore, AM2A-positive patients with shorter PBDD showed more CD8-positive lymphocyte infiltrates. Clinically, shorter PBDD was associated with higher serum creatine kinase levels, whereas longer PBDD was associated with a higher frequency of arrhythmia. Principal component analysis separated disease groups with high weight of muscle pathology components on two-dimensional plotting, although AM2A-positive myositis and IMNM partly overlapped. On logistic regression model analysis, we obtained high sensitivity (0.846) and specificity (0.842) for distinguishing them using clinical and pathological variables. This largest cohort study suggests that AM2A-positive myositis may be an independent subtype of AIM characterized by a chronic myositis with IMNM-like pathology, along with a high prevalence of cardiac involvement and respiratory muscle weakness.