Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c mice

Abstract

Objective To analyze the structure, specificity, and in vivo pathogenetic potential of 2 human anticardiolipin (aCL) monoclonal antibodies (MAb). Methods Human aCL IgG MAb were generated from hybridized Epstein‐Barr virus‐induced B cell lines from a healthy subject (MAb 519) and from a patient with primary antiphospholipid syndrome (MAb 516). Studies of antigen‐binding specificity and analysis of Ig V‐gene mutations were carried out. The MAb were independently injected into mated female BALB/c mice, and their effect on pregnancy outcome was compared with that of MAb 57, a highly mutated and antigen‐selected human IgG1λ rabies virus antibody. Results Both MAb 519 and MAb 516 utilized minimally mutated V_HDJ_H and V_κJ_κ gene segments and bound cardiolipin and other anionic phospholipids in the absence of β₂‐glycoprotein I (β₂‐GPI). The mice injected with aCL MAb displayed a significantly higher rate of fetal resorption and a significant reduction in fetal and placental weight as compared with those injected with MAb 57. These findings were accompanied by a finding of placental human IgG deposition and necrosis in the aCL MAb‐treated animals. Conclusion The results of this study indicate that human aCL IgG that are β₂‐GPI independent can induce pathology.