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, beta 2-glycoprotein I (beta 2-GPI). The aim of this study was to determine whether aCL purified from patients with infection also interact with beta 2-GPI. aCL purified from 23 patients with malaria, infectious mononucleosis, tuberculosis, hepatitis A or syphilis did not require the presence of beta 2-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 beta 2-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 beta 2-GPI, a plasma protein with anticoagulant activity.

Beta-2 glycoprotein I and its role in antiphospholipid syndrome—lessons from knockout mice

“…It is currently evident that the h 2 GPI ELISA has greater specificity and positive predictive value than the cardiolipin ELISA for the diagnosis of clinically significant APS [7,8]. These data confirmed previous experimental results on the role of h 2 GPI-dependent aPL in distinguishing between APS occurring in the setting of autoimmune diseases and the transient occurrence of aPL associated with infections [9]. In addition, it has been shown that most cases of clinically significant LA are associated with concomitant presence of anti-h 2 GPI antibodies in the sera of APS patients [10,11].…”

β2‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

“…Recently, it was demonstrated that the binding of aCL from patients with SLE and with the APS to solid-phase CL was dependent on the presence of a serum cofactor, P,-GPI (13)(14)(15)(16). In contrast, aCL from patients with infectious diseases without thrombosis bound to CL without P,-GPI (13,14,17). Anticardiolipin antibodies that are dependent on P2-GPI might therefore be more important in the APS than aCL that are independent of P,-GPI, but the specificity and the epitope of these aCL have not been clarified.…”

“…Anticardiolipin antibodies have also been found in sera from patients with various infectious diseases, but aCL from these latter patients (who rarely had thrombosis) bound to CL without P,-GPI (13,14,17). P,-GPI consists of 326 amino acids and binds to anionic PLs (14,1&21).…”

Origin and pathogenesis of antiphospholipid antibodies

“…Autoimmune and drug-induced IgG and IgM aPL require ß 2 GPI for binding to phospholipids (PL). In contrast, the PL binding of aPL associated with syphilis, HIV, or other infection-induced antibodies is inhibited by ß 2 GPI (63,77). This divergence in the phospholipid binding by autoimmune and infectious aPL supports the proposal of a different origin for these two groups of aPL (61,78).…”