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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.[1] As a result, AAHA are strongly implicated in autoimmune deep vein thrombosis.
Autoantibody | |
---|---|
Anti-Apolipoprotein, β-2 Glycoprotein 1 | |
Autoantigen Isoform | Apolipoprotein H |
Autoantigen gene | APOH |
Affected organ(s) | Cardiovascular |
Affected tissue(s) | serum |
Affected cell(s) | blood platelets |
Also Affected | serum proteins |
Associated Disease(s) | Idiopathic Thrombosis, Sclerosis, Systemic lupus erythematosus |
DR4-DQ3 | |
HLA associations | DR53 |
DRB1*0402 (DR4) | |
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 frequent 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.[citation needed]
The haplotype 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 disequilibrium 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.[citation needed]
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