Inclusion body myositis with human immunodeficiency virus infection: Four cases with clonal expansion of viral-specific T cells

Authors

  • Marinos C. Dalakas MD,

    Corresponding author
    1. Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
    • Neuromuscular Diseases Section, NINDS, NIH, Building 10, Room 4N248, 10 Center Drive, MSC 1382, Bethesda, MD 20892-1382
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  • Goran Rakocevic MD,

    1. Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Alexey Shatunov PhD,

    1. Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Lev Goldfarb MD,

    1. Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Raghavan Raju PhD,

    1. Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Mohammad Salajegheh MD

    1. Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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Abstract

Objective

Sporadic inclusion body myositis (sIBM), a common adult-onset myositis, is characterized by an antigen-driven inflammatory response and vacuolar degeneration. The cause is unknown. We report the association of sIBM with human immunodeficiency virus (HIV) infection and explore the clonality and viral specificity of the autoinvasive T cells.

Methods

Clinicopathological studies in four HIV-infected patients with IBM were performed. The clonal restriction of endomysial T cells, compared with peripheral blood, was examined by spectratyping. Immunohistochemical studies using human leukocyte antigen-A* 0201-gag tetramers and the most dominant Vb families were performed in serial muscle biopsy sections to examine whether clonally expanded autoinvasive T cells are viral specific and invade muscle fibers expressing the allele-specific monomorphic major histocompatibility complex class I antigen.

Results

Prominent clonal restriction of certain Vb families was noted among the endomysial T cells with evidence of in situ expansion. Approximately 10% of the autoinvasive CD8+ cells were human leukocyte antigen-A* 0201-HIV-gag specific and invaded muscle fibers expressing the specific human leukocyte antigen-A* 0201 allele. These cells belonged to restricted Vb families. The HIV gag antigen was present on several endomysial macrophages but not within the muscle fibers.

Interpretation

sIBM develops in patients who harbor HIV. In HIV-IBM, a subset of CD8+ T cells surrounding muscle fibers are viral specific and may play a role in the disease mechanism by cross-reacting with antigens on the surface of muscle fibers. This study provides a paradigm that a chronic viral infection in genetically susceptible individuals can trigger viral specific T cell clones that persist within the muscle and lead to development of sIBM. Ann Neurol 2007

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