PATHOGENIC ANTIBODIES IN WOMEN WITH OBSTETRIC FEATURES OF ANTIPHOSPHOLIPID SYNDROME WHO HAVE NEGATIVE TEST-RESULTS FOR LUPUS ANTICOAGULANT AND ANTICARDIOLIPIN ANTIBODIES

OBJECTIVE: Our goal was to determine whether women with clinical featu res of antiphospholipid syndrome but negative test results for lupus a nticoagulant and anticardiolipin antibodies have pathogenic antibodies not identified by currently used methods. STUDY DESIGN: Sera were obt ained from women with clinical features associated with antiphospholip id antibodies who had negative test results for lupus anticoagulant an d anticardiolipin antibodies (antiphospholipid syndrome-like). We stud ied (1) the effect of passive immunization with their purified immunog lobulin G fraction on murine pregnancy (n = 35) and (2) the presence o f antiphospholipid antibodies other than lupus anticoagulant or antica rdiolipin antibodies (n = 39). Sera were also retested for anticardiol ipin antibodies and lupus anticoagulant. RESULTS: Fetal loss occurred in 235 of 1088 (22%) pups in 137 mice immunized with immunoglobulin G fraction from antiphospholipid syndrome-like women compared with 23 of 402 (6%) pups in 53 control mice. Immunoglobulin G from 11 study pati ents resulted in the loss of at least one third of the exposed pups. F ive women had positive levels of antiphosphatidylserine antibodies (>9 9th percentile). All levels were low positive, and three women also ha d low-positive levels of anticardiolipin antibodies on repeat testing. Five of the 11 (45%) women whose immunoglobulin G fractions caused at least 33% fetal loss also had positive test results for antiphospholi pid antibodies. CONCLUSIONS: A subset of women with clinical disorders suspicious for antiphospholipid syndrome but who had negative test re sults for lupus anticoagulant and anticardiolipin antibodies by curren t methods have serum immunoglobulin G that is pathogenic to murine pre gnancy. Testing for pathogenic immunoglobulin G may provide additional means to identify women with an as yet uncharacterized immune conditi on. The clinical relevance of low levels of antiphospholipid antibodie s in these women remains unproved.