HUMAN ANTICARDIOLIPIN MONOCLONAL AUTOANTIBODIES CAUSE PLACENTAL NECROSIS AND FETAL LOSS IN BALB C MICE/

Objective. To analyze the structure, specificity, and in vivo pathogen etic potential of 2 human anticardiolipin (aCL) monoclonal antibodies (MAb). Methods. Human aCL IgG MAb were generated from hybridized Epste in-Barr virus-induced B cell lines from a healthy subject (MAb 519) an d from a patient with primary antiphospholipid syndrome (MAb 516). Stu dies of antigen-binding specificity and analysis of Ig V-gene mutation s were carried out. The MAb were independently injected into mated fem ale BALB/c mice, and their effect on pregnancy outcome was compared wi th that of MAb 57, a highly mutated and antigen-selected human IgG1 la mbda rabies virus antibody. Results. Both MAb 519 and MAb 516 utilized minimally mutated V(H)DJ(H) and V(kappa)J(kappa) gene segments and bo und cardiolipin and other anionic phospholipids in the absence of beta (2)-glycoprotein I (beta(2)-GPI). The mice injected with aCL MAb displ ayed a significantly higher rate of fetal resorption and a significant reduction in fetal and placental weight as compared with those inject ed with MAb 57. These findings were accompanied by a finding of placen tal human IgG deposition and necrosis in the aCL MAb-treated animals. Conclusion. The results of this study indicate that human aCL IgG that are beta(2)-GPI independent can induce pathology.