In autoimmune disease, anti-apolipoprotein H (AAHA) antibodies, also called anti-β₂ glycoprotein I antibodies, comprise a subset of

anti-cardiolipin antibodies Anti-cardiolipin antibodies (ACA) are antibodies often directed against cardiolipin and found in several diseases, including syphilis, antiphospholipid syndrome, livedoid vasculitis, vertebrobasilar insufficiency, Behçet's syndrome, idiopathic ...

and

lupus anticoagulant Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. Its name is a partial misnomer, as it is actually a prothrombotic antibody ''in vivo''. Lupus anticoagulant in living systems c ...

. 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 Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...

. Also, it was proposed that AAHA is responsible for

. 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

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

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 activities. AAHA interferes with

factor Xa Factor X, also known by the eponym Stuart–Prower factor, is an enzyme () of the coagulation cascade. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis. Fa ...

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.

Genetics

The haplotype

HLA-DR4 HLA-DR4 (DR4) is an HLA- DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world. Serology The serological identification of DR4 is ...

- DQ3 appears to play a role in the pathogenic AAHA production. The alleles primarily recognized are

HLA-DR53 HLA-DR53 is an HLA-DR serotype that recognizes gene products of HLA-DRB4 locus. There are 13 alleles at this locus that encode 7 proteins. DRB3, DRB4, and DRB5 are minor DR beta encoding loci, they have been recognized as having distinct evolution ...

(DRB4*01), DRB1*0402, DQA1*03, 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. HLA-DR7 may also be associated with these antibodies and the common haplotype association is the HLA-DR53 serotype.

References

{{DEFAULTSORT:Anti-Apolipoprotein Antibodies T