Anti-apolipoprotein antibodiesanti-apolipoprotein antibodies in blood, anti-apolipoprotein antibodies definition
In autoimmune disease, anti-apolipoprotein H AAHA antibodies, also called anti-β2 glycoprotein I antibodies, comprise a subset of anti-cardiolipin antibodies and lupus anticoagulant These antibodies are involved in sclerosis and are strongly associated with thrombotic forms of lupus As a result AAHA are strongly implicated in autoimmune deep vein thrombosis
Also, it was proposed that AAHA is responsible for lupus anticoagulant However, antiphospholipid antibodies bind phospholipids at sites similar to sites bound by anti-coagulants such as PAP1 sites and augment anti-coagulation activity This contrasts with the major, specific, activity of AAHA, defining a subset of anti-cardiolipin antibodies that specifically interacts with Apo-H AHAA only inhibits the anti-coagulation activity in the presence of Apo-H and the AAHA component of ACLA correlates with a history of frequent thrombosis This can be contrasted with lupus anticoagulant which inhibits agglutination in the presence of thrombin A subset of AHAA appear to mimic the activity of lupus anticoagulant and increase Apo-H binding to phospholipids These two activities can be differentiated by the binding to Apo-H domains, whereas binding to the 5th domain promotes that anti-coagulant activity binding to the more N-terminal domains promotes lupus anticoagulant-like activitiesstructure of Apolipoprotein H
AAHA interferes with factor Xa inhibition by Apo-H increasing factor Xa generation However, like Apo-H the Lupus anticoagulant inhibits factor Xa generation
AAHA also inhibited the autoactivation of factor XII while at high AAHA concentrations, factor XIIa activation increases at levels comparable to Apo-H that cause inhibition of factor XIIa activation A synchronized inhibition of factor XII autoactivation by Apo-H and AHAA has been suggested
The haplotype HLA-DR4-DQ3 appears to play a role in the pathogenic AAHA production The alleles primarily recognized are HLA-DR53 DRB401, DRB10402, DQA103, and possibly DQB10302 All of these alleles are in linkage disequilibrium in the DRB401:DRB10402:DQA10301:DQB10302 haplotype, also called DR4-DQ8 and also the DQA1:0303:DQB10301 haplotype, DR4-DQ73 However in European Americans which reflects a broad area of Europe in which the original studies were conducted only DR40402-DQ8 was found, indicating that the entire haplotype is involved
HLA-DR7 may also be associated with these antibodies and the common haplotype association is the HLA-DR53 serotype
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