Antibodies to phospholipids and nuclear antigens in patients with repeated abortions

Abstract

The frequency of positive tests for antibodies to nuclear antigens (antinuclear, deoxyribonucleic acid, Ro, La, Smith, and ribonucleoprotein) or to phospholipids was investigated in 82 patients with isolated repeated abortions. Patients with a positive antibody test (positive or negative deoxyribonucleic acid antibodies) appeared to be a separate subgroup of those with unexplained repeated abortions from those with antibodies to cardiolipin. A total of 13.1% of the 61 patients with unexplained repeated abortions had elevated levels of IgM and/or IgG anticardiolipin antibody, while none were found in patients with explained abortions (p less than 0.1). Enzyme-linked immunosorbent assays for antibodies binding to other phospholipids suggested that sera from patients with repeated abortions who had the lupus anticoagulant contained antibodies that were most often of the IgG class with affinity for negatively charged phospholipids. Binding of IgG but not IgM antibodies to cardiolipin correlated closely with that to other negatively charged phospholipids. The use of clotting tests for the lupus anticoagulant to screen patients with repeated abortions for associated autoantibodies is likely to significantly underestimate the extent of this clinical problem.

PIP: The relationship between antibodies to nuclear antigens and to the phospholipid cardiolipin was investigated in 82 patients with repeated abortions as an isolated complaint. The study also investigated: antibody binding to other phospholipids in anticardiolipin antibody-containing sera from patients in this study as well as from patients with repeated abortions initially ascertained through the presence of the lupus anticoagulant effect or a diagnosed autoimmune disease; and the possibility that the measurement of anticardiolipin antibody might overlook antibodies binding other important phospholipids. The 82 patients had been referred to the Pregnancy Loss Center of Medical Genetics for evaluation after at least 2 pregnancy losses. Laboratory evaluation for each patient with 2 losses included parental chromosome karyotypes, autoantibody studies, and luteal phase evaluation. An obstetric history was obtained from each patient, and patients were asked about a family history of autoimmune disease, alopecia, migraine headache, Reynaud's syndrome, arthralgias, pleuritic pain, easy bruising, or a photosensitive rash. 8 patients with known autoimmune disease and repeated abortions were excluded from the 1st part of this study. 61 patients were considered to have unexplained repeated abortions (group 2) and 21 to have explained repeated abortions (group 1). An enzyme-linked immunosorbent assay for IgG and IgM antibodies binding to the phospholipid cardiolipin was used, with the modification that a standard curve was obtained with the use of appropriate dilutions of sera with known IgG or IgM class anticardiolipin antibody. Those patients with a positive antibody test (positive or negative deoxyribonucleic acid antibodies) appeared to be a separate subgroup of those with unexplained repeated abortion from those with antibodies to cardiolipin. 13.1% of the 61 patients with unexplained repeated abortions had elevated levels of IgM and/or IgG anticardiolipin antibody; none were found in patients with explained abortions. This difference was statistically significant. Enzyme-linked immunosorbent assays for antibodies binding to other phospholipids suggested that sera from patients with repeated abortions who had the lupus anticoagulant contained antibodies that were most often of the IgG class with affinity for negatively charged phospholipids. The binding of IgG but not IgM antibodies to cardiolipin correlated closely with that to other negatively charged phospholipids.