Heterogeneity of the apolipoprotein H*3 allele and its role in affecting the binding of apolipoprotein H (beta 2-glycoprotein I) to anionic phospholipids.
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.
Kamboh
M I
MI
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15261, USA.
Wagenknecht
D R
DR
McIntyre
J A
JA
D000328:Adult; D000483:Alleles; D000838:Anions; D000911:Antibodies, Monoclonal / Q000032:analysis; D001053:Apolipoproteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D001667:Binding, Competitive / Q000276:immunology; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000032:analysis; D007525:Isoelectric Focusing; D008297:Male; D010718:Phosphatidylserines / Q000276:immunology / Q000378:metabolism*; D044469:Racial Groups; D053482:beta 2-Glycoprotein I
D000838:Anions; D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D010718:Phosphatidylserines; D053482:beta 2-Glycoprotein I