期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：12
页码：4788-4792
DOI：10.1073/pnas.0807319106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The inhibitory Fc-{gamma} receptor Fc{gamma}RIIB, expressed on myeloid and B cells, has a critical role in the balance of tolerance and autoimmunity, and is required for the antiinflammatory activity of intravenous Ig (IVIG) in various murine disease models. However, the function of Fc{gamma}RIIB and its regulation by IVIG in human autoimmune diseases are less well understood. Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy, and IVIG is widely used as a first-line initial and maintenance treatment. We found that untreated patients with CIDP, compared with demographically matched healthy controls, showed consistently lower Fc{gamma}RIIB expression levels on naive B cells, and failed to up-regulate or to maintain up-regulation of Fc{gamma}RIIB as B cells progressed from the naive to the memory compartment. Concomitantly, the rare -386C/-120A Fc{gamma}RIIB promoter polymorphism resulting in reduced promoter activity previously associated with autoimmune phenotypes was overrepresented in CIDP. Also, Fc{gamma}RIIB protein expression was up-regulated on monocytes and B cells after clinically effective IVIG therapy. Thus, our results suggest that the inhibitory Fc{gamma}RIIB is impaired at a critical B cell differentiation checkpoint in CIDP, and that modulating Fc{gamma}RIIB expression might be a promising approach to efficiently limit antibody-mediated immunopathology in CIDP.
关键词：autoimmunity ; human ; immunology ; Fc receptor ; CIDP
