A Phospholipid-β2-Glycoprotein I Complex Is an Antigen for Anticardiolipin Antibodies Occurring in Autoimmune Disease But Not with Infection

Abstract

Anticardiolipin antibodies (aCL) purified from patients with autoimmune disease have recently been shown to interact with a phospholipid-binding plasma protein, β₂-glycoprotein I (β₂-GPI). The aim of this study was to determine whether aCL purified from patients with infection also interact with β₂ -GPI.

aCL purified from 23 patients with malaria, infectious mononucleosis, tuberculosis, hepatitis A or syphilis did not require the presence of β₂-GPI to bind cardiolipin (CL). In contrast, aCL were purified from 11 out of 12 patients with autoimmune disease that bound CL only in the presence of β₂-GPI. Thrombotic complications appear to be associated with aCL occurring in autoimmune disease but not with aCL associated with infections. We postulate that this increased risk of thrombosis in the autoimmune group may be due to the presence of aCL that bind CL in association with β₂-GPI, a plasma protein with anticoagulant activity.

Keywords

Anticardiolipin antibodies β2-Glycoprotein I Thrombosis

Get full access to this article

View all access options for this article.

References

Pangborn MC A new serologically active phospholipid from beef heart. Proc Soc Exper Biol Med 1941 ; 48: 484-6.

Moore JE , Mohr CF Biologically false positive serological tests for syphilis. JAMA 1952; 150(5): 467-73.

Colaco CB , Mackie IJ , Irving W. , Machin SJ Anticardiolipin antibodies in viral infection. Lancet 1989; ii: 622 (letter).

Harris EN , Gharavi AE , Boey ML et al. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; ii: 1211-4.

Canosa RT , de Oliveira RM. Chlorpromazine-induced anticardiolipin antibodies and lupus anticoagulant: absence of thrombosis. Am J Hematol 1988; 27: 272-5.

Manoussakis MN , Tzioufas AG , Silas MP , Pange Pje , Goudevenos J. , Moutsopoulos HM High prevalence of anticardiolipin and other autoantibodies in a healthy elderly population. Clin Exper Immunol 1987; 69: 557-65.

Lockshin MD , Qamar T. , Druzin ML , Goei S. Antibody to cardiolipin, lupus anticoagulant, and fetal death. J Rheumatol 1987; 14: 259-62.

Harris EN , Asherson RA , Gharavi AE , Morgan SH , Derce G. , Hughes Grv. Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibody. Br J Haematol 1985 ; 59: 227-30.

Love PE , Santoro SA Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non SLE disorders. Ann Intern Med 1990; 112: 682-98.

10.

Harris EN , Gharavi AE , Wasley GD , Hughes Grv. Use of an enzyme-linked immunosorbent assay and of inhibition studies to distinguish between antibodies to cardiolipin from patients with syphilis or autoimmune disorders. J Infect Dis 1988; 157 (1): 23-31.

11.

McNeil HP , Simpson RJ , Chesterman CN , Krilis SA Antiphospholipid antibodies are directed against a complex antigen which includes a lipid binding inhibitor of coagulation: beta-2 glycoprotein-I (apolipoprotein H). Proc Natl Acad Sci USA 199(l; 87: 4120-4.

12.

Matsuura E. , Igarashi Y. , Fujimoto M. , Ichikawa K. , Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet 1990 ; 336: 177-8 (letter).

13.

Gharavi AE , Harris EN , Asherson RA , Hughes Grv. Anticardiolipin antibodies: isotype distribution and phospholipid specificity . Ann Rheum Dis 1987; 46: 1-6.

14.

McNeil HP , Chesterman CN , Krilis SA Binding specificity of lupus anticoagulants and anticardiolipin antibodies . Thromb Res 1988; 52: 609-19.

15.

Harris EN , Gharavi AE , Patel SP , Hughes Grv. Evaluation of the anticardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol 1987; 68: 215-22.

16.

McNeil HP , Krilis SA , Chesterman CN Purification of antiphospholipid antibodies using a new affinity method. Thromb Res 1988; 52: 641-8.

17.

McNeil HP , Shi W. , Chesterman CN et al. A new radioimmunoassay for β2-glycoprotein-I levels in plasma . (Submitted for publication)

18.

Thorell JI , Johansson BG Enzymatic iodination of polypeptides with 125I to high specific activity. Biochem Biophys Acta 1971; 251: 363-9.

19.

Rodbard D. , Munson PJ BCTIC Computer Code Collection (technical manual). Nashville , USA: Biomedical Computing Technology Information Center, 1984.

20.

McNeil HP , Chesterman CN , Krilis SA Anticardiolipin antibodies and lupus anticoagulants comprise separate antibody subgroups with different phospholipid binding characteristics. Br J Haematol 1989; 73: 506-13.

21.

Galli MD , Comfurius P. , Maasen C. et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990 ; 335: 1544-7.

22.

Wurm H. β2-Glycoprotein-I (apolipoprotein-H) interactions with phospholipid vesicles . Int J Biochem 1984; 16: 511-5.

23.

Harris EN , Gharavi AE , Loizou S. et al. Cross reactivity of antiphospholipid antibodies. J Clin Lab Immunol 1985; 16: 1-6.

24.

McNeil HP , Chesterman CN , Krilis SA Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991 ; 49: 193-280.

25.

Nimpf J. , Wurm H. , Kostner GM β2-Glycoprotein-I (apo H) inhibits the release reaction of human platelets during ADP-induced aggregation, Atherosclerosis 1987; 63: 109-14.

26.

Nimpf J. , Bevers EM , Bomans Phh et al. Prothrombinase activity of human platelets is inhibited by β2-glycoprotein-I . Biochem Biophys Acta 1986; 884: 142-9.