β2-Glycoprotein I/HLA class II complexes are novel autoantigens in antiphospholipid syndrome
Year: 2015
Type: article
Study design: Observational Study
Abstract: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy complications. β2-glycoprotein I (β2GPI) 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 β2GPI, 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 β2GPI/HLA class II complexes in the absence of phospholipids. In situ association between β2GPI and HLA class II was observed in placental tissues of APS patients but not in healthy controls. Furthermore, autoantibodies against β2GPI/HLA class II complexes mediated complement-dependent cytotoxicity against cells expressing the complexes. These data suggest that β2GPI/HLA class II complexes are a target in APS that might be involved in the pathogenesis.
Source: Blood
Authors: Kenji Tanimura, Hui Jin, Tadahiro Suenaga, Satoko Morikami, Noriko Arase, Kazuki Kishida, Kouyuki Hirayasu, Masako Kohyama, Yasuhiko Ebina, Shinsuke Yasuda, Tetsuya Horita, Kiyoshi Takasugi, Koichiro Ohmura, Ken Yamamoto, Ichiro Katayama, Takehiko Sasazuki, Lewis L. Lanier, Tatsuya Atsumi, Hideto Yamada, Hisashi Arase
Institutions: Research Institute for Microbial Diseases, The University of Osaka, Kobe University, The University of Osaka, Immunology Frontier Research Center, The University of Osaka, Hokkaido University, Dogo Onsen Hospital, Kyoto University, Medical Institute of Bioregulation, Kyushu University, Kyushu University, Kyushu University Institute for Advanced Study, University of California, San Francisco, Japan Science and Technology Agency
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Analysis of tissue macrophage development and its role in vivo, Autoantibody to beta2GPI/MHC class II and obstetrical complications, NK Memory, Mechanisms of viral entry and membrane fusion of herpesvirus, G3142121030, Evaluation study of antioxidative abilities of the keto-carotenoid species found in photosynthetic bacteria, G3208073714, The mechanism how RasGRP4 promotes proliferation of synovial fibroblasts in rheumatoid arthritis, Functional and genetic diversity of the activating receptor to recognize microbially cleaved antibody, G5878503461, G6718509927, Mechanism of herpesvirus infection, G7879866177
OpenAlex ID: W1985773947