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 are strongly associated with thrombotic forms of lupus. 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. 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 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.
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.