Proteomic profiling of antigens in circulating immune complexes associated with each of seven autoimmune diseases.

OBJECTIVE: Immune complexes (ICs) trigger humoral immune responses. Therefore, the identification of constituent antigens within ICs would have very different clinical significance than identification of free antigens.

DESIGN AND METHODS: Here, we applied immune complexome analysis of serum to the study of seven major autoimmune diseases-anti-neutrophil cytoplasmic antibody-associated vasculitis, Takayasu's arteritis, mixed connective tissue disease, dermatomyositis, Sjögren's syndrome, systemic scleroderma, and systemic lupus erythematosus-and healthy donors to comprehensively identify antigens incorporated into circulating ICs and to find disease-specific antigens.

RESULTS: We identified 468 distinct IC-associated antigens using this method. Importantly, 62 of those antigens were disease-specific antigens, and there were at least three disease-specific antigens for each of the seven autoimmune diseases. Of the disease-specific antigens identified, coiled-coil domain-containing protein 158 and spectrin were identified as potential autoantigens important to SSc and SS pathogenesis, respectively; notable titin and spectrin autoantibodies are reportedly found in SSc and SS patients, respectively.

CONCLUSION: Immune complexome analysis may be generally applicable to the study of the relationship between ICs and autoimmune diseases in animals and humans.