Autoantibodies produced at the site of tissue damage provide evidence of humoral autoimmunity in inclusion body myositis.
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.
Department of Neurology, Yale School of Medicine, New Haven, Connecticut, United States of America.
Arundhati
A
Ray
Anthony A
AA
Amato
Elizabeth M
EM
Bradshaw
Kevin J
KJ
Felice
Daniel B
DB
DiCapua
Jonathan M
JM
Goldstein
Ingrid E
IE
Lundberg
Richard J
RJ
Nowak
Hidde L
HL
Ploegh
Eric
E
Spooner
Qian
Q
Wu
Simon N
SN
Willis
Kevin C
KC
O'Connor
D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D001324:Autoantigens / Q000276:immunology / Q000302:isolation & purification; D015551:Autoimmunity; D016022:Case-Control Studies; D002460:Cell Line; D003893:Desmin / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification; D051379:Mice; D009124:Muscle Proteins / Q000276:immunology / Q000302:isolation & purification; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000097:blood / Q000276:immunology*; D011485:Protein Binding
D001323:Autoantibodies; D001324:Autoantigens; D003893:Desmin; D007074:Immunoglobulin G; D009124:Muscle Proteins