Immune complexome analysis of antigens in circulating immune complexes isolated from patients with IgG4-related dacryoadenitis and/or sialadenitis

Abstract

Objectives. IgG4-related disease (IgG4-RD) is characterized by various serological abnormalities. Some patients with IgG4-RD present with hypergammaglobulinemia, hypocomplementemia, and autoantibodies recognizing rheumatoid factors and nuclear factors. However, whether IgG4-RD is an autoimmune disease remains unclear.

Methods. Here, we used immune complexome analysis to comprehensively identify constituent antigens of circulating immune complexes isolated from 10 patients with IgG4-related dacryoadenitis and/or sialadenitis (IgG4-RDS) which is one condition associated with IgG4-RD.

Results. We detected each of 125 distinct antigens in independent samples from two or more patients with IgG4-RDS. Of them, 17 antigens were found to be specific to patients with IgG4-RDS by comparing 125 antigens with all the antigens found in other connective tissue diseases (antineutrophil cytoplasmic antibody-associated vasculitis, Takayasu's arteritis, mixed connective tissue disease, dermatomyositis, Sjögren's syndrome, systemic scleroderma, and systemic lupus erythematosus) or healthy donors. The number of disease-specific antigens associated with IgG4-RDS was comparable to those autoimmune diseases.

Conclusions. Studies of the 17 IgG4-RDS-specific antigens might lead to a better understanding of the pathogenesis of IgG4-RD, but further study of the prevalence of these CIC-associated antigens that involves a selective and sensitive assay will be needed to determine their potential as diagnostic or pathogenic biomarkers.

Keywords:

• Autoimmune disease
• IgG4-related disease
• Immune complex
• Immune complexome analysis
• Tandem mass spectrometry

Acknowledgement

This work was supported by a Grant-in-Aid for Young Scientist (B), Grant-in-aid for Scientific Research (C) and challenging Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Grant-in-Aid for Scientific Research from Nagasaki University, the Joint Research Promotion Project of Nagasaki University Graduate School of Biomedical Sciences in 2013, and the Research Foundation for Pharmaceutical Sciences.

Conflict of interest

Research Funding: K. Ohyama, Eisai Co., Ltd.