PMID- 25733579
OWN - NLM
STAT- MEDLINE
DCOM- 20150803
LR  - 20210202
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 125
IP  - 18
DP  - 2015 Apr 30
TI  - beta2-Glycoprotein I/HLA class II complexes are novel autoantigens in 
      antiphospholipid syndrome.
PG  - 2835-44
LID - 10.1182/blood-2014-08-593624 [doi]
AB  - Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by 
      thrombosis and/or pregnancy complications. beta2-glycoprotein I (beta2GPI) 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 beta2GPI, 
      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 
      beta2GPI/HLA class II complexes in the absence of phospholipids. In situ association 
      between beta2GPI and HLA class II was observed in placental tissues of APS patients 
      but not in healthy controls. Furthermore, autoantibodies against beta2GPI/HLA class 
      II complexes mediated complement-dependent cytotoxicity against cells expressing 
      the complexes. These data suggest that beta2GPI/HLA class II complexes are a target 
      in APS that might be involved in the pathogenesis.
CI  - (c) 2015 by The American Society of Hematology.
FAU - Tanimura, Kenji
AU  - Tanimura K
AD  - Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka 
      University, Suita, Osaka, Japan; Department of Obstetrics and Gynecology, Kobe 
      University Graduate School of Medicine, Kobe, Hyogo, Japan;
FAU - Jin, Hui
AU  - Jin H
AD  - Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka 
      University, Suita, Osaka, Japan; Laboratory of Immunochemistry, Immunology 
      Frontier Research Center, Osaka University, Suita, Osaka, Japan;
FAU - Suenaga, Tadahiro
AU  - Suenaga T
AD  - Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka 
      University, Suita, Osaka, Japan; Laboratory of Immunochemistry, Immunology 
      Frontier Research Center, Osaka University, Suita, Osaka, Japan;
FAU - Morikami, Satoko
AU  - Morikami S
AD  - Department of Obstetrics and Gynecology, Kobe University Graduate School of 
      Medicine, Kobe, Hyogo, Japan; Laboratory of Immunochemistry, Immunology Frontier 
      Research Center, Osaka University, Suita, Osaka, Japan;
FAU - Arase, Noriko
AU  - Arase N
AD  - Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka 
      University, Suita, Osaka, Japan; Department of Dermatology, Osaka University 
      Graduate School of Medicine, Suita, Osaka, Japan;
FAU - Kishida, Kazuki
AU  - Kishida K
AD  - Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka 
      University, Suita, Osaka, Japan; Laboratory of Immunochemistry, Immunology 
      Frontier Research Center, Osaka University, Suita, Osaka, Japan;
FAU - Hirayasu, Kouyuki
AU  - Hirayasu K
AD  - Laboratory of Immunochemistry, Immunology Frontier Research Center, Osaka 
      University, Suita, Osaka, Japan;
FAU - Kohyama, Masako
AU  - Kohyama M
AD  - Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka 
      University, Suita, Osaka, Japan; Laboratory of Immunochemistry, Immunology 
      Frontier Research Center, Osaka University, Suita, Osaka, Japan;
FAU - Ebina, Yasuhiko
AU  - Ebina Y
AD  - Department of Obstetrics and Gynecology, Kobe University Graduate School of 
      Medicine, Kobe, Hyogo, Japan;
FAU - Yasuda, Shinsuke
AU  - Yasuda S
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Hokkaido, Japan;
FAU - Horita, Tetsuya
AU  - Horita T
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Hokkaido, Japan;
FAU - Takasugi, Kiyoshi
AU  - Takasugi K
AD  - Department of Internal Medicine, Center for Rheumatic Diseases, Dohgo Spa 
      Hospital, Matsuyma, Ehime, Japan;
FAU - Ohmura, Koichiro
AU  - Ohmura K
AD  - Department of Rheumatology and Clinical Immunology, Kyoto University Graduate 
      School of Medicine, Kyoto, Kyoto, Japan;
FAU - Yamamoto, Ken
AU  - Yamamoto K
AD  - Division of Genome Analysis, Medical Institute of Bioregulation, and.
FAU - Katayama, Ichiro
AU  - Katayama I
AD  - Department of Dermatology, Osaka University Graduate School of Medicine, Suita, 
      Osaka, Japan;
FAU - Sasazuki, Takehiko
AU  - Sasazuki T
AD  - Institute for Advanced Study, Kyushu University, Fukuoka, Fukuoka, Japan;
FAU - Lanier, Lewis L
AU  - Lanier LL
AD  - Department of Microbiology and Immunology and the Cancer Research Institute, 
      University of California San Francisco, San Francisco, CA; and.
FAU - Atsumi, Tatsuya
AU  - Atsumi T
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Hokkaido, Japan;
FAU - Yamada, Hideto
AU  - Yamada H
AD  - Department of Obstetrics and Gynecology, Kobe University Graduate School of 
      Medicine, Kobe, Hyogo, Japan;
FAU - Arase, Hisashi
AU  - Arase H
AUID- ORCID: 0000-0002-1153-3166
AD  - Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka 
      University, Suita, Osaka, Japan; Laboratory of Immunochemistry, Immunology 
      Frontier Research Center, Osaka University, Suita, Osaka, Japan; Core Research 
      for Evolutional Science and Technology, Japan Science and Technology Agency, 
      Honcho Kawaguchi, Saitama, Japan.
LA  - eng
GR  - R01 AI068129/AI/NIAID NIH HHS/United States
GR  - AI068129/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150302
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Antiphospholipid)
RN  - 0 (Autoantibodies)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (beta 2-Glycoprotein I)
SB  - IM
CIN - Blood. 2015 Apr 30;125(18):2741. PMID: 25931579
MH  - Adult
MH  - Aged
MH  - Antibodies, Antiphospholipid/*blood/immunology
MH  - *Antiphospholipid Syndrome/blood/immunology
MH  - Autoantibodies/immunology
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Female
MH  - HEK293 Cells
MH  - Histocompatibility Antigens Class II/*immunology/metabolism
MH  - Humans
MH  - Lupus Erythematosus, Systemic/blood/immunology
MH  - Male
MH  - Multiprotein Complexes/*immunology
MH  - Pregnancy
MH  - Pregnancy Complications/blood/immunology
MH  - beta 2-Glycoprotein I/*immunology/metabolism
PMC - PMC4424631
EDAT- 2015/03/04 06:00
MHDA- 2015/08/04 06:00
PMCR- 2016/04/30
CRDT- 2015/03/04 06:00
PHST- 2014/08/04 00:00 [received]
PHST- 2015/02/02 00:00 [accepted]
PHST- 2015/03/04 06:00 [entrez]
PHST- 2015/03/04 06:00 [pubmed]
PHST- 2015/08/04 06:00 [medline]
PHST- 2016/04/30 00:00 [pmc-release]
AID - S0006-4971(20)31745-6 [pii]
AID - 2014/593624 [pii]
AID - 10.1182/blood-2014-08-593624 [doi]
PST - ppublish
SO  - Blood. 2015 Apr 30;125(18):2835-44. doi: 10.1182/blood-2014-08-593624. Epub 2015 
      Mar 2.