Localized and peripheral autoantibodies: evidence of humoral autoimmunity in patients with inclusion body myositis (159.21)

Abstract Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The disease is viewed to be T cell mediated. However, emerging data suggests that B cells may play a role in IBM. To further the understanding of IBM immunopathology and explore the role of the humoral autoimmune response in IBM, we searched for autoantibodies both in the periphery and at the site of tissue damage. Peripheral autoantibodies that recognized muscle-derived cells were demonstrated in IBM serum using both immunohistochemistry and flowcytometry. To focus on the site of tissue injury, we examined the immunoglobulin-secreting plasma cells that infiltrate IBM muscle. A series of single, tissue-associated plasma cells were isolated from IBM muscle. Recombinant immunoglobulins (rIgG) produced from these cells were used as molecular tools to search for autoantigens. Flow cytometry and immunoblotting revealed that these tissue-derived rIgGs recognized human muscle tissue-associated antigens. To identify the target of the rIgGs, a multi-step protein separation scheme and mass spectrometry were employed. Desmin, a major intermediate filament protein expressed in muscle, was identified as a candidate autoantigen for one IBM rIgG. Specificity to desmin was confirmed with a solid-phase assay. Collectively, these data indicate that IBM autoimmunity includes a humoral component.