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Anti-apolipoprotein antibodies

anti-apolipoprotein antibodies in blood, anti-apolipoprotein antibodies definition

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

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

structure of Apolipoprotein H

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


The haplotype HLA-DR4-DQ3 appears to play a role in the pathogenic AAHA production The alleles primarily recognized are HLA-DR53 DRB401, DRB10402, DQA103, and possibly DQB10302 All of these alleles are in linkage disequilibrium in the DRB401:DRB10402:DQA10301:DQB10302 haplotype, also called DR4-DQ8 and also the DQA1:0303:DQB10301 haplotype, DR4-DQ73 However in European Americans which reflects a broad area of Europe in which the original studies were conducted only DR40402-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


  1. ^ Viard JP, Amoura Z, Bach JF 1991 "" Comptes Rendus de l'Académie des Sciences, Série III in French 313 13: 607–12 PMID 1782567 
  2. ^ Sammaritano LR, Gharavi AE, Soberano C, Levy RA, Lockshin MD 1992 "Phospholipid binding of antiphospholipid antibodies and placental anticoagulant protein" J Clin Immunol 12 1: 27–35 doi:101007/BF00918270 PMID 1372614 
  3. ^ Galli M, Bevers EM, Comfurius P, Barbui T, Zwaal RF 1993 "Effect of antiphospholipid antibodies on procoagulant activity of activated platelets and platelet-derived microvesicles" Br J Haematol 83 3: 466–72 doi:101111/j1365-21411993tb04672x PMID 8485053 
  4. ^ Tsutsumi A, Matsuura E, Ichikawa K, et al 1996 "Antibodies to beta 2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus" Arthritis Rheum 39 9: 1466–74 doi:101002/art1780390905 PMID 8814057 
  5. ^ Takeya H, Mori T, Gabazza EC, et al 1997 "Anti-beta2-glycoprotein I beta2GPI monoclonal antibodies with lupus anticoagulant-like activity enhance the beta2GPI binding to phospholipids" J Clin Invest 99 9: 2260–8 doi:101172/JCI119401 PMC 508058  PMID 9151800 
  6. ^ Shi W, Chong BH, Hogg PJ, Chesterman CN 1993 "Anticardiolipin antibodies block the inhibition by beta 2-glycoprotein I of the factor Xa generating activity of platelets" Thromb Haemost 70 2: 342–5 PMID 8236146 
  7. ^ Schousboe I, Rasmussen MS 1995 "Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I" Thromb Haemost 73 5: 798–804 PMID 7482406 
  8. ^ Hattori N, Kuwana M, Kaburaki J, Mimori T, Ikeda Y, Kawakami Y 2000 "T cells that are autoreactive to beta2-glycoprotein I in patients with antiphospholipid syndrome and healthy individuals" Arthritis Rheum 43 1: 65–75 doi:101002/1529-013120000143:1<65::AID-ANR9>30CO;2-I PMID 10643701 
  9. ^ Galeazzi M, Sebastiani GD, Tincani A, et al 2000 "HLA class II alleles associations of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus" Lupus 9 1: 47–55 doi:101177/096120330000900109 PMID 10715100 
  10. ^ Ioannidis JP, Tektonidou MG, Vlachoyiannopoulos PG, et al 1999 "HLA associations of anti-beta2 glycoprotein I response in a Greek cohort with antiphospholipid syndrome and meta-analysis of four ethnic groups" Hum Immunol 60 12: 1274–80 doi:101016/S0198-88599900122-6 PMID 10626742 
  11. ^ Klitz W, Maiers M, Spellman S, et al 2003 "New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans" Tissue Antigens 62 4: 296–307 doi:101034/j1399-0039200300103x PMID 12974796 

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Anti-apolipoprotein antibodies

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