Eosinophilic myocarditis associated with anti-mitochondrial M2 antibodies: a mechanism underlying the onset of myocarditis

Abstract

A 68-year-old woman was diagnosed with eosinophilic myocarditis. Laboratory tests showed abnormally increased eosinophils (50.2%) on the leucocyte counts (17 600 /μL). An endomyocardial biopsy (EMB) was performed from the right ventricular septum and revealing numerous eosinophilic infiltrations. Immediately after starting prednisolone 30 mg/day, her eosinophil count normalized, we gradually decreased treatment. Three months later, she became aware of poor mobility in her right lower limb when prednisolone reduced to 5 mg. Femoral magnetic resonance imaging revealed a high-intensity area in her right biceps femoris muscle by short T1 inversion recovery method (Panel A, arrows). Testing for relevant antibodies showed positivity for anti-mitochondrial M2 only, prompting a diagnosis of myositis with anti-mitochondrial M2 antibody. Skeletal muscle biopsy was performed. Immunohistochemistry for pyruvate dehydrogenase complex-E2 subunit (PDC-E2), an antigen for anti-mitochondrial M2 antibodies, showed granular cytoplasmic staining in myocytes (Panel B). We also performed immunohistochemistry for PDC-E2 in the previous EMB samples, and found granular staining in the cytoplasm of all cardiomyocytes (Panel C). Reviewing the electron microscopy of EMB samples revealed degenerated mitochondria (Panel D, arrows) in cardiomyocytes. Comparable samples from a patient with eosinophilic myocarditis negative for anti-mitochondrial M2 antibodies revealed no immunostaining for myocardial PDC-E2 (Panel E). Myositis with anti-mitochondrial M2 antibodies is characterized by high frequency of cardiac involvement, similar to myocarditis. Mitochondrial damage released PDC-E2 into the cytoplasm, prompting inflammatory activation against those damaged cells. The presence of such immune reactions in cardiomyocytes and skeletal muscle could result in myocarditis and myositis, respectively, as seen in the present patient.