Anti-apolipoprotein antibodies

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 strongly associate with thrombitic forms of lupus.^[1]. As a result AAHA are strongly implicated in autoimmune deep vein thrombosis.

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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^[2]. This contrasts with the major, specific, activity of AAHA, defining a subset of anti-cardiolipin antibodies that specifically interacts with Apo-H.^[3] AHAA only inhibits the anti-coagulation activity in the presence of Apo-H and the AAHA component of ACLA correlates with a history of freqeunt thrombosis.^[4]. 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.^[5] 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 activities.

  AAHA interferes with factor Xa inhibition by Apo-H increasing factor Xa generation. However, like Apo-H the Lupus anticoagulant inhibits factor Xa generation.^[6]

AAHA also inhibited the autoactivation of factor XII ^[7] 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.

Genetics

The hapolotype HLA-DR4-DQ3 appears to play a role in the pathogenic AAHA production. The alleles primarily recognized are HLA-DR53^[8] (DRB4*01), DRB1*0402^[9], DQA1*03^[10], and possibly DQB1*0302. All of these alleles are in linkage disequilbrium in the DRB4*01:DRB1*0402:DQA1*0301:DQB1*0302 haplotype, also called DR4-DQ8 and also the DQA1:0303:DQB1*0301 haplotype, DR4-DQ7.3. However in European Americans which reflects a broad area of Europe in which the original studies were conducted only DR4(0402)-DQ8 was found, indicating that the entire haplotype is involved.^[11]

HLA-DR7 may also be associated with these antibodies and the common haplotype association is the HLA-DR53 serotype.

References