β2-Glycoprotein I/HLA class II complexes are novel autoantigens in antiphospholipid syndrome

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

研究成果: Contribution to journalArticle査読

32 被引用数 (Scopus)

抄録

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy complications. b2-glycoprotein I (b2GPI) 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 b2GPI, 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 b2GPI/HLA class II complexes in the absence of phospholipids. In situ association between b2GPI and HLA class II was observed in placental tissues of APS patients but not in healthy controls. Furthermore, autoantibodies against b2GPI/HLA class II complexes mediated complement-dependent cytotoxicity against cells expressing the complexes. These data suggest that b2GPI/HLA class II complexes are a target in APS that might be involved in the pathogenesis. (Blood. 2015;125(18):2835-2844)

本文言語英語
ページ(範囲)2835-2844
ページ数10
ジャーナルBlood
125
18
DOI
出版ステータス出版済み - 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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