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Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome?

Servizio di Immunologia Clinica, Spedali Civili, Brescia

Angela Tincani

Servizio di Immunologia Clinica, Spedali Civili, Brescia

Laura Spatola

Servizio di Immunologia Clinica, Spedali Civili, Brescia

Flavio Allegri

Servizio di Immunologia Clinica, Spedali Civili, Brescia

Enrica Prati

Servizio di Immunologia Clinica, Spedali Civili, Brescia

Roberto Cattaneo

Servizio di Immunologia Clinica, Spedali Civili, Brescia

Guido Valesini

Clinica Medica I, Università La Sapienza, Roma

Nicoletta Del Papa

Clinica Medica , Universita degli Studi, Milano, Italy

Pierluigi Meroni

Clinica Medica , Universita degli Studi, Milano, Italy

Anticardiolipin (aCL) and anti-beta2-glycoprotein I(antiß2GPI) antibodies have been shown in animal models as not cross-reacting antibody populations. This observation prompted us to prove if anti-ß2GPI exist in human sera by using a reliable method and then to investigate if these are independent from aCl antibodies. We have developed a new ELISA for the detection of anti-ß2GPI antibodies employing the coating of the protein in carbonate buffer to irradiated microtitre plates and the filtration of serum samples, that makes irrelevant the binding to the uncoated wells. IgG F(ab)₂ fragments from IgG positive sera were shown bind ß2GPI, providing that the binding was a specific antibody binding, mediated by the antigen binding site of the antibody molecule; moreover the antibodies were not able to differentiate native and delipidated ß2GPI coated plates, making a possible role of a phospholipid contaminant unlikely. On the other hand, the phosphorus content of native as well as delipitated ß2GPI was undetectable. IgG, but not IgM, anti-ß2GPI antibodies were classically inhibited by the addition of soluble ß2GPI, while cardiolipin liposomes appear to modify the reaction in a completely different way, possibly by the described interaction between cardiolipin and ß2GPI. The application of the new ELISA to the study of patients has shown that: (1) the presence of anti-ß2GPI is statistically associated with the presence of aCL antibodies (P < 0.0001), (2) anti-ß2GPI antibodies are related to the classical features of antiphospholipid syndrome (thrombosis: P < 0.001; fetal loss: P < 0.001) while, in this series of patients, aCl antibodies are not (thrombosis: P < 0.126; fetal loss: P < 0.061).

Key Words: Anti-beta2-glycoprotein I • Antiphospholipid antibodies • anticardiolipin antibodies • antiphospholipid syndrome

Lupus, Vol. 4, No. 2, 122-130 (1995)
DOI: 10.1177/096120339500400208


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