Rheumatology (Oxford). 2026 Jan 2:keaf670. doi: 10.1093/rheumatology/keaf670. Online ahead of print.
ABSTRACT
OBJECTIVES: Cardiac involvements in idiopathic inflammatory myopathies (IIM) is rare but potentially severe. Anti-mitochondrial M2 antibody (AMA-M2) has been implicated in cardiac involvements, but the association remains under-explored. This study aims to evaluate the clinical, pathological, and prognostic features of AMA-M2 IIM.
METHODS: This historic prospective cohort included IIM patients hospitalized at Peking Union Medical College Hospital between 2008 and 2020. Outcomes were prospectively collected through the PROMIS registry. Cox regression models were employed to identify risk factors of cardiac involvements and mortality.
RESULTS: Among 987 IIM patients, 55 (6%) were AMA-M2 positive. These patients exhibited higher rates of polymyositis (56% vs 23.5%, p< 0.001), and elevated baseline gamma-glutamyl transferase (GGT) (78.0 vs 35.0, p< 0.001) and alkaline phosphatase (ALP) (85.0 vs 64.0, p< 0.001). Throughout disease courses, AMA-M2 positive patients had significantly higher rates of cardiac involvements (60% vs 12.9%, p< 0.001), including arrhythmias (56%), heart failure (44%), and pulmonary hypertension (31%). Some of the muscle biopsies showed features consistent with immune-mediated necrotizing myopathy (IMNM), cardiac biopsies demonstrating structural degeneration with minimal inflammation, and liver biopsies confirming early-stage primary biliary cholangitis (PBC). Multivariate COX analysis identified AMA-M2 positivity as an independent risk factor for cardiac involvements (HR 3.156, p< 0.001). Despite frequent cardiac manifestations, long-term survival did not differ between AMA-M2 positive and negative patients (mean survival: 103.9 months vs 98.0 months, p= 0.86).
CONCLUSION: AMA-M2 positivity defines an IIM subgroup with significant cardiac involvements, an immune-mediated inflammatory muscle histology, but not necessarily worse long-term survival. These findings highlight the need for early recognition and tailored management of AMA-M2 IIM.
PMID:41485097 | DOI:10.1093/rheumatology/keaf670
