Autoantibodies produced at the site of tissue damage provide evidence of humoral autoimmunity in inclusion body myositis

• Published in: PloS one 2012-10, Vol.7 (10), p.e46709-e46709
• Main Authors: Ray, Arundhati, Amato, Anthony A, Bradshaw, Elizabeth M, Felice, Kevin J, DiCapua, Daniel B, Goldstein, Jonathan M, Lundberg, Ingrid E, Nowak, Richard J, Ploegh, Hidde L, Spooner, Eric, Wu, Qian, Willis, Simon N, O'Connor, Kevin C
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antigens; Arthritis; Autoantibodies; Autoantibodies - blood; Autoantibodies - chemistry; Autoantibodies - isolation & purification; Autoantigens; Autoantigens - immunology; Autoantigens - isolation & purification; Autoimmunity; B cells; Biology; Biomedical research; Biopsy; Biotechnology; Brain research; Case-Control Studies; Cell Line; Cell lines; Cytometry; Damage; Desmin; Desmin - immunology; Desmin - isolation & purification; Disease; Flow cytometry; Hospitals; Humans; Immune response; Immune response (humoral); Immune system; Immunity (Physiology); Immunity, Humoral; Immunoblotting; Immunoglobulin G - blood; Immunoglobulin G - chemistry; Immunoglobulin G - isolation & purification; Immunoglobulins; Immunology; Inflammation; Inflammatory diseases; Intermediate filament proteins; Lymphocytes; Mass spectrometry; Mass spectroscopy; Medicin och hälsovetenskap; Medicine; Mice; Multiple sclerosis; Muscle Proteins - immunology; Muscle Proteins - isolation & purification; Muscle, Skeletal - immunology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Musculoskeletal diseases; Musculoskeletal system; Myositis; Myositis, Inclusion Body - blood; Myositis, Inclusion Body - immunology; Neurology; Pathogenesis; Pathology; Patients; Plasma; Plasma cells; Protein Binding; Proteins; Rheumatology; T cell receptors; Target recognition; Tissues
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046709

Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG). These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens.