Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta 2-glycoprotein I (beta 2GPI) or apolipoprotein H has been described as a necessary cofactor for antiphospholipid antibody (aPA) binding in ELISA. Some investigators disagree with the beta 2-GPI requirement whereas data from other laboratories indicate that beta 2GPI, not phospholipid (PL), is the antigen for aPA. To investigate the cofactor we have produced three IgG1 monoclonal antibodies (mAb) to human beta 2GPI; 3G9, 1B4 and 3D11. Western blot analyses showed the mAb to bind human beta 2GPI (40 kDa), but no reactivity was observed with adult or fetal bovine sera. In contrast, rabbit anti-beta 2GPI reacted with both human and bovine sera. None of the mAb reacted with phosphatidylserine (PS) or cardiolipin (CL) by ELISA. There were no significant differences in ELISA binding to purified beta 2GPI when the mAb were adjusted to the same concentration. mAb 3G9 and 1B4 gave stronger signals in ELISA after beta 2GPI bound to PS; the increase for 3G9 was significantly greater than for 1B4 (p < 0.002). mAb 3D11 was unique inasmuch as it failed to recognize beta 2PGI bound to PS. In comparison, the rabbit anti-beta 2GPI was unaffected by PS-beta 2GPI binding. These observations indicate that the mAb recognize three distinct epitopes on beta 2GPI. The data suggest that beta 2GPI undergoes conformational changes subsequent to binding PL. Our findings are consistent with the hypothesis that aPA recognize a beta 2GPI neotope formed subsequent to binding PL.
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PMID:Changes in beta 2-glycoprotein I antigenicity induced by phospholipid binding. 768 33

Apolipoprotein H (apoH, protein; APOH, gene) has been implicated as a necessary cofactor for the binding of certain autoimmune antiphospholipid antibodies to anionic phospholipids. APOH exhibits genetically determined structural polymorphism with the occurrence of four alleles. Recently three IgG1k monoclonal antibodies (mAb) to human apoH, designated 3G9, 1B4, and 3D11, have been produced. The mAb 3D11 does not recognize apoH bound to anionic phospholipids in contrast to mAb 3G9 and 1B4, which recognize free and phospholipid-bound apoH. In this investigation we have determined the reactivity of the three mAb with four APOH allele products and the binding ability of these allele products with anionic phospholipids. The mAb 3G9 and 1B4, like the polyclonal anti-apoH, were equally reactive with all four allelic products, but the 3D11 recognized only the APOH*3 allele product. In the 159 APOH*3 carriers tested from five ethnic groups, the reactivity of mAb 3D11 was observed with all the Chinese but none of the African blacks. For the U.S. whites and Polynesians 89% and 75%, respectively, of the APOH*3 allele products were recognized by 3D11, while 87% of the U.S. blacks with this allele had no 3D11 reactivity. These data show that the APOH*3 allele, originally identified as a single entity by the polyclonal anti-apoH, is heterogeneous with at least one distinct variation based on mAb 3D11 reactivity. Our data also demonstrate that the apoH from certain homozygous APOH*3 individuals is unable to bind to anionic phospholipids. Such ethnic-specific apoH variations could play a significant role in the binding properties of autoimmune antiphospholipid antibodies to anionic phospholipids.
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PMID:Heterogeneity of the apolipoprotein H*3 allele and its role in affecting the binding of apolipoprotein H (beta 2-glycoprotein I) to anionic phospholipids. 770 32