부산대학교 도서관

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 VHDJH and VκJκ 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 areβ2-GPI independent can induce pathology.