Inflammatory Myopathy Associated with Antimitochondrial Antibodies

Abstract & Commentary

Synopsis: Specific antibody-mediated inflammatory myopathies are being better defined and classified within the spectrum of dermatomyositis and polymyositis.

Source: Maeda MH, et al. Inflammatory myopathy associated with antimitochondrial antibodies. Brain 2012;135:1767-1777.

The authors report that 24 of 212 (11.3%) consecutive patients with inflammatory myopathies had elevated levels of antimitochondrial antibodies, which typically are associated with primary biliary cirrhosis. Eight of the 24 had cardiac arrhythmias, with six exhibiting low ejection fractions. Of those with arrhymias, five had supraventricular tachycardia, two had ventricular tachycardia, and one had A-V block. Six of the patients had pulmonary involvement with decreased vital capacity, two of whom required respiratory support. Six patients were not aware of weakness at the time of diagnosis, but had progressive muscle atrophy, with four exhibiting elevated creatine kinase levels and two cardiac arrhythmia. Seven of the 24 patients had biliary cirrhosis, with more frequent cardiac involvement. In pathological studies, all had inflammatory infiltrates in muscle biopsies, with 13 exhibiting chronic myopathic changes and six granulomatous lesions.

Statistically, the presence of antimitochondrial antibodies was more frequently associated with a chronic course, presence of muscle atrophy, cardiopulmonary involvement, and pathological finding of granulomatous inflammation, in comparison to patients without antimitochondrial antibodies. The inflammatory myopathies associated with antimitochondrial antibodies may thus form a characteristic subgroup.


The inflammatory myopathies constitute a heterogeneous group of disorders that traditionally include polymyositis (PM), dermatomyositis (DM), and sporadic inclusion body myositis (sIBM). DM is characterized by complement mediated microangiopathy with perifascicular inflammation, whereas PM and sIBM are characterized by the presence of cytotoxic T-cells that invade MCH-I expressing muscle fibers, which in sIBM also contain vacuoles with amyloid. Necrotizing autoimmune myositis (NAM) is a more recently recognized entity that is mediated by macrophages, and characterized by necrotic muscle fibers, absence of inflammatory infiltrates, and deposition of C5b-9 complexes on non-MHC-I expressing muscle cells.1,2 Modifications to this general classification also have been proposed based on other pathological features.3 Granulomatous inflammation traditionally has been associated with sarcoidosis, but as reported by Maeda et al, is apparently also present in association with antimitochondrial antibodies.

Myositis specific autoantibodies include anti-Jo-1 antibodies in polymositis or dermatomyositis,4 anti-signal recognition particle (SRP) antibodies in necrotizing myopathy,5 and occasionally anti-p155, and MJ antibodies in select patients.6 Other autoantibodies that are less specific for myositis include anti-synthetase antibodies, anti-PM/Sc antibodies, anti-Ku antibodies, anti-U1-5RNP antibodies, anti-CADM-140 antibodies, and anti-HMGCR antibodies. Such antibodies can help identify distinct clinical syndromes, as is reported in the current paper by Maeda et al, for antimitochondrial antibodies.

Autoantibodies can be pathogenic or serve as disease markers. Valivil et al reported that necrotizing myositis associated with anti-SRP antibodies, which is resistant to traditional immunosuppressive agents, can respond to therapy with rituximab, a B-cell depleting monoclonal antibody.5 Research into immune mechanisms in the inflammatory myopathies can thus lead to improved clinical classification, and development of more targeted therapies that can be tested in clinical trials.


1. Dalakas MC. Pathogenesis and therapies of immune mediated myopathies. Autoimmun Rev 2012;11:203-206.

2. Cong L, et. al. Role of C5b-9 expression in skeletal muscle blood vessels in necrotizing myopathy. Nan Fang Yi Ke Da Xue Xue Bao 2012;32:714-717.

3. Pestronk A. Acquired immune and inflammatory myopathies: pathological classification. Curr Opin Rheumatol 2011;23: 595-604.

4. Stone KB, et. al. Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis Rheum 2007;56:3125-3131.

5. Valivil R, et. al. Rituximab therapy for myopathy associated with anti-signal recognition particle antibodies: A case series. Arthritis Care Res 2010;62; 1328-34.

6. Miller FW. New approaches to the assessment and treatment of the idiopathic inflammatory myopathies. Ann Rheum Dis 2012; 71 (supp II): i82-i85