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 IgG1lambda rabies virus antibody. RESULTS: Both MAb 519 and MAb 516 utilized minimally mutated V(H)DJ(H) and VkappaJkappa gene segments and bound cardiolipin and other anionic phospholipids in the absence of beta2-glycoprotein I (beta2-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 beta2-GPI independent can induce pathology.
|Titolo:||Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c mice|
|Parole Chiave:||Animals ; Fetal Resorption ; Humans ; Cardiolipins ; Mice ; Amino Acid Sequence ; Mice, Inbred BALB C ; Antibodies, Anticardiolipin ; Pregnancy ; Antibodies, Monoclonal ; Necrosis ; Base Sequence ; Autoantibodies ; Placenta ; Adult ; Molecular Sequence Data ; Immunoglobulin G ; Binding Sites, Antibody ; Epitopes ; Female|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||giu-1998|
|Digital Object Identifier (DOI):||10.1002/1529-0131(199806)41:6<1026::AID-ART9>3.0.CO;2-1|
|Appare nelle tipologie:||01 - Articolo su periodico|