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

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.

• 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
• Journal: Blood (Blood) Vol. 125 Issue 18 Pg. 2835-44 (Apr 30 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 25733579 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

• Antibodies, Antiphospholipid
• Autoantibodies
• Histocompatibility Antigens Class II
• Multiprotein Complexes
• beta 2-Glycoprotein I

Topics

• Adult
• Aged
• Antibodies, Antiphospholipid (blood, immunology)
• Antiphospholipid Syndrome (blood, immunology)
• Autoantibodies (immunology)
• Case-Control Studies
• Cells, Cultured
• Female
• HEK293 Cells
• Histocompatibility Antigens Class II (immunology, metabolism)
• Humans
• Lupus Erythematosus, Systemic (blood, immunology)
• Male
• Multiprotein Complexes (immunology)
• Pregnancy
• Pregnancy Complications (blood, immunology)
• beta 2-Glycoprotein I (immunology, metabolism)