Journal
LUPUS
Volume 25, Issue 12, Pages 1288-1298Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0961203316638165
Keywords
Apolipoprotein B100; anticardiolipin antibody; beta2-glycoprotein I; lipoprotein-associated phospholipase A2; oxidized LDL; tissue factor
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Funding
- Japanese Ministry of Health, Labor and Welfare
- Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Grants-in-Aid for Scientific Research [15H04690, 26293230, 25461466, 15K09514] Funding Source: KAKEN
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Objective The objective of this paper is to elucidate the not yet known plasma molecule candidates involved in the induction of tissue factor (TF) expression mediated by 2GPI-dependent anticardiolipin antibody (aCL/2GPI) on monocytes. Methods Human serum incubated with FLAG-2GPI was applied for affinity chromatography with anti- FLAG antibody. Immunopurified proteins were analyzed by a liquid chromatography coupled with mass spectrometry (LC-MS). TF mRNA induced by the identified molecules on monocytes was also analyzed. Results Apolipoprotein B100 (APOB) was the only identified serum molecule in the MS search. Oxidized LDL, containing APOB as well as ox-Lig1 (a known ligand of 2GPI), was revealed as a 2GPI-binding molecule in the immunoprecipitation assay. TF mRNA was markedly induced by oxidized LDL/2GPI complexes with either WBCAL-1 (monoclonal aCL/2GPI) or purified IgG from APS patients. The activities of lipoprotein-associated phospholipase A2, one of the component molecules of oxidized LDL, were significantly higher in serum from APS patients than in those from controls. Conclusion APOB (or oxidized LDL) was detected as a major 2GPI binding serum molecule by LC-MS search. Oxidized LDL/aCL/2GPI complexes significantly induced TF expressions on monocytes. These data suggest that complexes of oxidized LDL and aCL/2GPI may have a crucial role in the pathophysiology of APS.
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