The role of β2-glycoprotein I in the antiphospholipid syndrome

Abstract

Antiphospholipid antibodies were originally thought to bind negatively-charged (aniomic) phospholipids. Current evidence suggests that the target antigen is considerably more complex and includes β₂-glycoprotein I, a phospholipid-binding plasma protein. Our under standing of the pathophysiology of the antiphospholipid syndrome has increased exponen tially with a number of studies into the interactions of antiphospholipid antibodies and β₂-glycoprotein I.

Keywords

antiphospholipid syndrome antiphospholipid antibodies β2-glycoprotein I

Get full access to this article

View all access options for this article.

References

McNeil HP , Chesterman CN and Krilis SA Immunology and Clinical Importance of antiphospholipid antibodies. Advances in Immunology, 1991; 193-279.

Love PE and Santoro SA Antiphospholipid Antibodies: Anticardiolipin and the Lupus Anticoagulant in Systemic Lupus Erthematosus (SLE) and in Non-SLE Disorders. Annals of Internal Medicine 1990; 112: 682-698.

McNeil HP et al. Antiphospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2-glycoprotein-I (apolipoprotein H). Proc Natl Acad Sci USA 1990; 87: 4120-4124.

Galli M. et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990 ; 335: 1544-1547.

Hunt, JE et al. A phospholipid-β2-glycoprotein-I complex is the antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infections. Lupus 1992; 1: 75-81.

Reid Kbm and Day AJ Structure-function relationships of the complement components. Immunology Today 1989; 10: 177-180. 7. Kandiah DA and Krilis SA Beta-2-Glycoprotein I. Lupus 1994; 3: 207-212.

Arvieux J. et al. Measurement of antiphospholipid antibodies by ELISA using Beta-2-glycoprotein I as an antigen. J Immunol Meth 1991; 143: 223-229.

Viard JP , Amoura Z. and Bach JF Association of anti-beta-2-glycoprotein-I antibodies with lupus-type circulating anticoagulants and thrombosis in systemic lupus erythematosus . Am J Med 1992; 93(2): 181-186.

Pierangeli SS et al. Are immunoglobulins with lupus anticoagulant activity specific for phospholipids? Br J Haematol 1993; 85: 124-132.

10.

Pierangeli SS et al. β2-glycoprotein-I (β 2GPI) enhances cardiolipin binding activity but is not the antigen for antiphospholipid antibodies. Br J Haematol 1992; 82: 565-570.

11.

Matsuura E. et al. Anticardiolipin antibodies recognise β 2glycoprotein-I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179: 457-462.

12.

Hunt JE and Krilis SA The fifth domain of β2-glycoprotein-I contains a phospholipid binding site (Cys 281-Cys 288) and a region recognised by anticardiolipin antibodies. J Immunol 1994; 152: 653-659.

13.

Hunt JE , Simpson RJ and Krilis SA Identification of a region of β2-glycoprotein-I critical for lipid binding and anti-cardiolipin antibody cofactor activity. Proc Nat Acac Sci 1993; 92: 2141-2145.

14.

Wang M-X. , Kandiah DA , Ichikawa K. et al. Epitope specificity of monoclonal anti-β2-glycoprotein-I antibodies derived from patients with the antiphospholipid syndrome. J of Immunology 1995; 155: 1629-1636.

15.

Roubey RA Eisenberg RA , Harper MF , Winfield JB Anticardiolipin autoantibodies recognise β2-glycoprotein-I in the absence of phospholipid: Importance of Ag density and bivalent binding . J of Immunology 1995; 154: 954-960.