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


CONCLUSIONS
The results of this study indicate that human aCL IgG that are beta2-GPI independent can induce pathology.
Ikematsu
W
W
Cornell University Medical College, New York, New York, USA.
Luan
F L
FL
La Rosa
L
L
Beltrami
B
B
Nicoletti
F
F
Buyon
J P
JP
Meroni
P L
PL
Balestrieri
G
G
Casali
P
P
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics; D002308:Cardiolipins / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005327:Fetal Resorption / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009336:Necrosis; D010920:Placenta / Q000276:immunology* / Q000473:pathology*; D011247:Pregnancy
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D002308:Cardiolipins; D000939:Epitopes; D007074:Immunoglobulin G