autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

, 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 s ...

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 cause ...

. 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. Fac ...

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 HLA-DR7 (DR7) is a HLA- DR serotype that recognizes the DRB1*0701 to *0705 gene products. Serology The serological reaction of DR7 is excellent for *0701. The serology of *0703 to *0705 to *0709, and *0711 to *0714 serotypes is unknown. DRB1*0 ...

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

References

{{DEFAULTSORT:Anti-Apolipoprotein Antibodies T