Anti-β2 GPI Research Articles

Anti beta 2glycoprotein I antibodies and lupus anticoagulant in patients with recurrent pregnancy loss: prevalence and clinical significance.

Anticardiolipin antibodies (aCL) were found to recognize beta 2glycoprotein I (beta 2GPI) structure altered by its interaction with an oxygen modified solid phase surface by gamma-ray radiation. Lupus anticoagulant (LA) has been reported to comprise anti prothrombin antibodies, anti factor X antibodies and anti beta 2GPI antibodies. The present study focuses on the possible association between antibodies against the altered beta 2GPI structure (anti beta 2GPI antibodies) and LA in patients with recurrent pregnancy loss. Moreover, the clinical significance of both subgroups of so-called antiphospholipid antibodies were investigated to cast light on the controversy of whether aCL and LA are risk factors for pregnancy losses. One hundred and ninety five women with a history of two or more unexplained consecutive miscarriages and 100 control pregnant women were tested. Lupus anticoagulant was detected by the dilute phospholipid activated partial thromboplastin time. Anti beta 2GPI antibodies were measured by the ELISA method using commercially oxygenated microtiter plates. Twenty two (11.3%) and 19 (9.7%) of the 195 recurrent aborters were, respectively, positive for LA and anti beta 2GPI antibodies. Seven (3.6%) of the aborters had both of them. None of the control pregnant women had LA. Three of the control pregnant women had anti beta 2GPI antibodies. Nine (40.9%) of 22 aborters with positive-LA had a history of miscarriages in the second trimester as compared to 8 (4.6%) of 173 aborters with negative-LA. (P = 0.000007, Odds ratio = 14.3). None of the 12 aborters with anti beta 2GPI antibodies but no LA had a history of second trimester-fetal loss. These results support the hypothesis that aCL and LA define two distinct but partly related populations and that aCL include two subtypes of antibodies, with and without LA activity. LA and anti beta 2GPI antibodies appear to be associated with pregnancy loss, with LA being linked not only to abortions in the first trimester but also to miscarriages in the second trimester.

Reactivity to β2 Glycoprotein I Clearly Differentiates Anticardiolipin Antibodies from Antiphospholipid Syndrome and Syphilis

Anticardiolipin antibodies (aCL) detected by standard ELISA are found in association with autoimmune and infectious diseases. It is now recognized that beta 2 glycoprotein I (beta 2GPI) is a cofactor for aCL binding to cardiolipin (CL). To examine differences in cofactor requirements, aCL positive sera from patients with the antiphospholipid syndrome (APS) and syphilis were studied. Using an ELISA with human purified beta 2GPI adsorbed onto irradiated plates, we detected high binding activity in 29 out of 35 samples from APS patients and low in only 1 out of 37 aCL positive syphilis sera. Moreover, a good correlation (r = 0.79) was also observed in the former group between aCL and anti beta 2GPI. Whole IgG and affinity purified IgG aCL from APS patients did not bind to CL in the absence of beta 2GPI, but recognized beta 2GPI on irradiated plates in the absence of phospholipids. In contrast, IgG purified from syphilis patients only bound to CL alone. Taken together, these data indicate that performing both ELISA (aCL and anti beta 2GPI) it could be possible to distinguish aCL from autoimmune or infectious diseases.

Platelet Activating Properties of Murine Monoclonal Antibodies to β2-Glycoprotein I

Previously developed murine monoclonal antibodies (MAbs) to human beta 2-glycoprotein I (beta 2 GPI), a plasma protein required for the binding of anti-phospholipid antibodies, were studied for anti-platelet reactivity and influence on platelet function. The six MAbs (IgG1 isotype) tested interacted with both intact and fixed platelets in a beta 2 GPI-dependent manner. Carbamylated beta 2 GPI was still recognized by MAbs but was unable to mediate platelet-antibody binding. MAbs induced aggregation and secretion responses of platelets in platelet-rich plasma (PRP) and whole blood, provided subthreshold concentrations of weak agonists (i.e. ADP or adrenaline) were added. When aggregation in PRP was evaluated by a counting technique instead of turbidometrically, the sole addition of MAbs led to a rapid fall in single platelets. Triggering gel-filtered platelets with MAbs together with beta 2 GPI, but not its carbamylated form, led to platelet activation after a lag time, as monitored by aggregometry, measurements of ATP and beta-thromboglobulin secretion and calcium mobilization. F(ab')2 fragments of one of the MAbs failed to activate platelets but inhibited the responses to the whole antibody. This process thus depends on MAbs binding to platelets through both Fab and Fc domains, as confirmed by the suppression of platelet responses upon pretreatment with the anti-Fc gamma RII MAb IV.3. Aggregation and secretion induced by MAbs plus beta 2 GPI did not require exogenous fibrinogen and were variably inhibited in the presence of acetyl salicylic acid, apyrase or Ca2+, depending on the concentrations used for the two proteins.(ABSTRACT TRUNCATED AT 250 WORDS)