PMID- 9627012 OWN - NLM STAT- MEDLINE DCOM- 19980707 LR - 20111117 IS - 0004-3591 (Print) IS - 0004-3591 (Linking) VI - 41 IP - 6 DP - 1998 Jun TI - Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c mice. PG - 1026-39 AB - 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. FAU - Ikematsu, W AU - Ikematsu W AD - Cornell University Medical College, New York, New York, USA. FAU - Luan, F L AU - Luan FL FAU - La Rosa, L AU - La Rosa L FAU - Beltrami, B AU - Beltrami B FAU - Nicoletti, F AU - Nicoletti F FAU - Buyon, J P AU - Buyon JP FAU - Meroni, P L AU - Meroni PL FAU - Balestrieri, G AU - Balestrieri G FAU - Casali, P AU - Casali P LA - eng GR - AR-40908/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Antibodies, Anticardiolipin) RN - 0 (Antibodies, Monoclonal) RN - 0 (Autoantibodies) RN - 0 (Cardiolipins) RN - 0 (Epitopes) RN - 0 (Immunoglobulin G) SB - IM CIN - Arthritis Rheum. 1999 Aug;42(8):1783-4. PMID: 10446886 MH - Adult MH - Amino Acid Sequence MH - Animals MH - Antibodies, Anticardiolipin/*immunology MH - Antibodies, Monoclonal/*immunology MH - Autoantibodies/*immunology MH - Base Sequence MH - Binding Sites, Antibody/genetics MH - Cardiolipins/immunology MH - Epitopes/immunology MH - Female MH - Fetal Resorption/*immunology MH - Humans MH - Immunoglobulin G/immunology MH - Mice MH - Mice, Inbred BALB C MH - Molecular Sequence Data MH - Necrosis MH - Placenta/*immunology/*pathology MH - Pregnancy EDAT- 1998/06/17 00:00 MHDA- 1998/06/17 00:01 CRDT- 1998/06/17 00:00 PHST- 1998/06/17 00:00 [pubmed] PHST- 1998/06/17 00:01 [medline] PHST- 1998/06/17 00:00 [entrez] AID - 10.1002/1529-0131(199806)41:6<1026::AID-ART9>3.0.CO;2-1 [doi] PST - ppublish SO - Arthritis Rheum. 1998 Jun;41(6):1026-39. doi: 10.1002/1529-0131(199806)41:6<1026::AID-ART9>3.0.CO;2-1.