期刊
BLOOD
卷 125, 期 18, 页码 2835-2844出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-08-593624
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资金
- Japan Science and Technology Agency, Core Research for Evolutional Science and Technology
- Ministry of Education, Culture, Sports, Science & Technology Japan [22133009, 22133003, 25133705]
- Japan Society for the Promotion of Science [23390112, 24590584, 25460565, 26870334]
- National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI068129]
- Grants-in-Aid for Scientific Research [24115005, 23390112, 15K09514, 24590584, 15K05577, 26462489, 25460565, 26870334, 26117714, 22133009, 22133003] Funding Source: KAKEN
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy complications. beta 2-glycoprotein I (beta 2GPI) complexed with phospholipid is recognized as a major target for autoantibodies in APS; however, less than half the patients with clinical manifestations of APS possess autoantibodies against the complexes. Therefore, the range of autoantigens involved in APS remains unclear. Recently, we found that human leukocyte antigen (HLA) class II molecules transport misfolded cellular proteins to the cell surface via association with their peptide-binding grooves. Furthermore, immunoglobulin G heavy chain/HLA class II complexes were specific targets for autoantibodies in rheumatoid arthritis. Here, we demonstrate that intact beta 2GPI, not peptide, forms a complex with HLA class II molecules. Strikingly, 100 (83.3%) of the 120 APS patients analyzed, including those whose antiphospholipid antibody titers were within normal range, possessed autoantibodies that recognize beta 2GPI/HLA class II complexes in the absence of phospholipids. In situ association between beta 2GPI and HLA class II was observed in placental tissues of APS patients but not in healthy controls. Furthermore, autoantibodies against beta 2GPI/HLA class II complexes mediated complement-dependent cytotoxicity against cells expressing the complexes. These data suggest that beta 2GPI/HLA class II complexes are a target in APS that might be involved in the pathogenesis.
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