Variable Cardiac Responses to Immunosuppressive Therapy in Anti-Mitochondrial Antibody-Positive Myositis.

We describe a case of anti-mitochondrial antibody-positive myositis associated with cardiovascular involvement. An electrophysiological study (EPS) showed binodal dysfunction, and cardiac magnetic resonance (CMR) imaging revealed left ventricular dysfunction with diffuse, patchy T2 high-intensity areas and late gadolinium enhancement indicative of inflammation and fibrosis. The left ventricular dysfunction was successfully treated with immunosuppressive therapy as documented by CMR. Persistence of conduction system dysfunction was confirmed by EPS, and a pacemaker was implanted. CMR and EPS concisely documented the variable cardiac response to treatment in anti-mitochondrial antibody-positive myositis. We demonstrate the utility of cardiac investigations in this rare disorder.

Cytokine expression in the muscle of HIV-infected patients: evidence for interleukin-1 alpha accumulation in mitochondria of AZT fibers.

To evaluate the possible role of cytokines in human immunodeficiency virus (HIV)-associated muscular disorders, we performed immunocytochemistry for interleukin-1 alpha, -1 beta, and -6 and tumor necrosis factor-alpha on frozen muscle biopsy specimens from HIV-infected patients with various myopathies (HIV polymyositis in 5, HIV-wasting syndrome in 5, zidovudine myopathy in 10) and from seronegative individuals (normal muscle in 2, mitochondrial cytopathies in 10). The HIV-infected patients showed positive reactivities in vessels (interleukin-1) and in inflammatory cells (mainly interleukin-1 and tumor necrosis factor-alpha), including perivascular hemosiderin-laden macrophages in 5 patients. In zidovudine myopathy, a majority of AZT fibers (i.e., ragged-red fibers with marked myofibrillar changes) showed mild to marked expression of interleukin-1. Expression of interleukin-1 in the other mitochondrial myopathies was much weaker. Interleukin-1 beta messenger RNA was demonstrated in muscle fibers by in situ hybridization, implying that interleukin-1 was produced in muscle cells. Immunoelectron microscopy showed that interleukin-1 alpha was mainly bound to mitochondrial membranes in AZT fibers. Proinflammatory and destructive effects of the studied cytokines might be responsible for several myopathological changes observed in HIV-infected patients, including inflammation and hemosiderin deposits in muscle tissue, and prominent myofibrillar breakdown in AZT fibers.

Antigenic determinants of T lymphocyte alpha beta receptor and other leukocyte surface proteins as differential markers of skeletal muscle regeneration: detection of spatially and timely restricted patterns by MAM microscopy.

Different stages of human muscle regeneration have been identified by multiple antigen-mapping (MAM) microscopy at the level of a novel marker system. This immunofluorescence method allows the selective imaging of numerous antigen signals from cells or tissue sections. It is shown that 2 monoclonal antibodies (mAbs) against the common region of the alpha beta T lymphocyte antigen receptor (alpha beta and alpha TCR chains) and 3 mAbs against the leukocyte surface antigens Leu8, OKM5 and Leu19 recognize regenerating muscle cells at different time points of regeneration in human muscle sections. Paradoxically, these epitopes are not expressed by T lymphocytes or other mononuclear leukocytes invading regenerating muscle. Hence, presence of the corresponding antigens in muscle fibers may exclude their expression by muscle-invasive immune cells suggesting a function in muscle-specific cell-to-cell recognition. Simultaneous localization of these epitopes in Duchenne dystrophy reveals 10 different phenotypes of regenerating and normal infantile muscle cells due to different developmental stages during the myocyte differentiation. In adult muscle (mitochondrial myopathy) segmental muscle fiber necrosis is accompanied by high concentration of alpha beta/alpha TCR epitopes in the intact fiber ends, which are the target sites of myogenesis. The same sites are invaded by OKM5+ endomysial capillary sprouts that terminate at the tip of the alpha beta/alpha TCR reactive fiber ends. These hitherto unrecognized initial events of segmental muscle regeneration seem to be followed by fragmentation of the invasive capillaries into single endothelial cells, which then switch from the OKM5+ Leu19- through the OKM5+ Leu19+ to the OKM5- Leu19+ phenotype. This cell type exhibits the typical features of Leu19+ myogenic stem cells described earlier. The findings may give rise to a concept of muscle repair, in which the alpha beta/alpha TCR-related antigen, concentrated in fiber stumps, might provide positional information for invading endothelial cells. These cells appear to be a source of myogenic stem cells for regeneration.