Anticardiolipin Antibodies in Infections are Heterogenous in Their Dependency on β 2-Glycoprotein I: Analysis of Anticardiolipin Antibodies in Leprosy

Abstract

We studied the effect of β₂-GPI on binding of antibodies in sera from patients with leprosy and patients with the antiphospholipid syndrome (APS) to CL in enzyme-linked immunosorbent assays (ELISAs). Increased levels of IgG aCL were detected in 59 of 61 leprosy patients' sera by the standard aCL-ELISA in the presence of bovine β₂-GPI and in 60 of the 61 leprosy patients' sera by the modified aCL-ELISA without β₂-GPI. When tested by both aCL-ELISAs on the same plate, 10/31 leprosy sera and 9/10 APS sera bound better in the standard aCL-ELISA, 16/31 leprosy sera bound better in the modified aCL-ELISA and in five leprosy and one APS sera the difference was not significant. A dose-dependent enhancing effect of β₂-GPI on the leprosy and APS sera binding to CL was confirmed using purified human β₂-GPI. Enhanced binding was seen if β₂-GPI was added either before or together with the test serum. In 11/61 leprosy sera increased levels of IgG antibodies against β₂-GPI were found by ELISA. Leprosy anti-β₂-GPI antibodies appear to be a separate antibody population recognizing only β₂-GPI adsorbed on the ELISA plate. These results demonstrate heterogeneity of leprosy aCL with respect to their β₂-GPI requirement for binding to CL.

Keywords

Leprosy Anticardiolipin antibodies Antiphospholipid antibodies β2-glycoprotein 1

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References

Harris EN Annotation: antiphospholipid antibodies. Br J Haematol 1990; 74: 1-9.

Derksen Rhwm , Kater L. Lupus anticoagulant: revival of an old phenomenon . Clin Exp Rheumatol 1985; 3: 349-57.

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

Tomer Y. , Buskila D. , Shoenfeld Y. Pathogenic significance and diagnostic value of lupus autoantibodies. Int Arch Allergy Immunol 1993; 100: 293-306.

Sammaritano LR , Gharavi AE , Lockshin MD Antiphospholipid antibody: immunologic and clinical aspects. Semin Arthritis Rheum 1990 ; 20: 81-96.

Tomer Y. , Shoenfeld Y. The relationship between the lupus anticoagulant, anticardiolipin antibodies and antiphospholipid antibodies. Isr J Med Sci 1990; 28: 38-40.

Hunt JE , McNeil HP , Morgan GJ , Crameri RM , Krilis SA A phospholipid-β2-glycoprotein 1 complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. Lupus 1992; 1: 75-81.

Matsuura E. , Igarashi Y. , Fujimoto M. et al. Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J Immunol 1992; 148: 3885-91.

McNeil HP , Hunt JE , Krilis SA New aspects of anticardiolipin antibodies. Clin Exp Rheumatol 1990; 8: 525-7.

10.

Sammaritano LR , Lockshin MD , Gharavi AE Antiphospholipid antibodies differ in aPL cofactor requirement. Lupus 1992; 1: 83-90.

11.

Cabral AR , Cabiedes J. , Alarcon-Segovia D. , Sanchez-Guerrero J. Phospholipid specificity and requirement of β2-glycoprotein-1 for reactivity of antibodies from patients with primary antiphospholipid syndrome. J Autoimmunity 1992; 5: 787-801.

12.

Gharavi AE Antiphospholipid cofactor. Stroke 1992; 23: 17-110.

13.

Pierangeli S. , Davis S. , Harris EN Comparison of the effect of β2-glycoprotein 1 on the anticardiolipin binding to phospholipids. Arthritish Rheum 1992; 35: S70 (abstract).

14.

McNeil HP , Simpson RJ , Chesterman CN , Krilis SA Antiphospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2-glycoprotein 1 (apilipoprotein H). proc Natl Acad Sci USA 1990; 87: 4120-4.

15.

Blank M. , Cohen J. , Toder V. , Shoenfeld Y. Induction of antiphospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc Natl Acad Sci USA 1991; 88: 3069-73.

16.

Bakimer R. , Fishman P. , Blank M. , Sredni B. , Djaldetti M. , Shoenfeld Y. Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3). J Clin Invest 1992; 89: 1558-63.

17.

Furukawa F. , Kashihara M. , Imamura S. , Ohshio G. , Hamashima Y. Evaluation of anticardiolipin antibody and its cross reactivity in sera of patients with lepromatous leprosy. Arch Dermatol Res 1986; 278: 317-9.

18.

Gharavi AE , Lockshin MD Enhancement of anti-phospholipid antibody activity Tween 20. J Immunol Methods 1988; 114: 277.

19.

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.

20.

Arvieux J. , Roussel B. , Jacob MC , Colomb MG Measurement of antiphospholipid antibodies by ELISA using β2-glycoprotein 1 as an antigen. J Immunol Methods 1991; 143: 223-9.

21.

Wurm H. β2-glycoprotein-1 (apolipoprotein-H) interactions with phospholipid vesicles . Int J Biochem 1984; 16: 511-5.

22.

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

23.

Viard JP , Amoura Z. , Bach JF Association of anti-β2-glycoprotein 1 antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus. Am J Med 1992; 93: 181-6.

24.

Shapiro SS , Essex D. , Thiagarjan P. , Love T. Immunologic specificity of anticardiolipin antibodies. Blood 1991; 78 (Suppl. 1): 221 (abstract).

25.

Wagenknecht DR , McInture JA Changes in β2-glycoprotein 1 antigenicity induced by phospholipid binding. Thrombos Haemostas 1993; 69: 361-5.

26.

Tomer Y. , Shoenfeld Y. The significance of natural autoantibodies. Immunol Invest 1988; 17: 389-424.

27.

Gharavi AE , Harris EN , Sammaritano LR , Pierangeii SS , Wen J. Do patients with antiphospholipid syndrome have autoantibodies to β2-glycoprotein 1? J Lab Clin Med 1993; 122: 426-31.

28.

Pierangeli SS , Harris EN , Davis SA , DeLorenzo G. β2-glycoprotein 1 (β2-GP1) enhances cardiolipin binding activity but is not the antigen for antiphospholipid antibodies . Br J Haematol 1992 ; 82: 565-70.

29.

Hoeg JM , Segal P. , Gregg RE et al. Characterization of plasma lipids and lipoproteins in patients with β2-glycoprotein 1 (apolipoprotein H) deficiency. Atherosclerosis 1985; 55: 25-34.