PubMed · 4734092
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B D Schmitt, H P Martin, G Nellhaus, J Cravens, B W Camp, K Jordan. 1973. The hyperactive child.. https://doi.org/10.1177/000992287301200310
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Demonstration of autoimmune antiphospholipid antibodies (aPA) to negatively charged phospholipids (PL) in an enzyme-linked immunosorbent assay (ELISA) requires the presence of certain phospholipid-binding plasma proteins, eg, beta 2-glycoprotein I. We found a requirement for plasma against the electrically neutral or zwitterionic phospholipid, phosphatidylethanolamine (PE). Two of these PE-binding plasma proteins were identified as high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). We studied anti-PE antibody (aPE) seropositive plasma from 13 patients with SLE and/or recurrent spontaneous abortions by using partially purified kininogens and kininogen binding proteins from adult bovine serum isolated by carboxymethyl (CM)-papain affinity chromatography. Eleven of 13 sera recognized a kininogen-PE complex and/or a kininogen-binding protein-kininogen-PE complex. Some aPE-positive patient sera were shown to recognize highly purified HMWK and LMWK by ELISA only when the kininogens were presented on a PE substrate. These aPE sera did not recognize PE, HMWK, or LMWK when they were presented independently as the sole antigens on the ELISA plates. Other aPE-positive sera that did not react with PE-bound HMWK or LMWK reacted with the CM-papain column eluate when it was bound to PE, which suggests that these aPE recognize factor XI or prekallikrein, which normally bind to HMWK. The aPE ELISA reactivity of two patient sera were inhibited by preincubation of the CM-papain column eluate in the ELISA plate. These data show that most aPE are not specific for PE but require the presence of certain PL-binding plasma proteins that are kininogens or proteins in complex with kininogens. Our studies indicate that aPE bind to different plasma proteins than those implicated in anionic PL, aPA ELISA reactivity.
OBJECTIVE: To compare the meta-analytic results from published literature vs those obtained from pooling original patient data. DATA SOURCES: Individual patient data from 15 completed or ongoing trials on paternal white blood cell immunization as treatment for recurrent miscarriage were obtained through the American Society for Reproductive Immunology. STUDY SELECTION: Only randomized controlled trials were selected. Within these eight selected trials, 202 patients were from four published studies, 43 were added by the same investigators after publication, and 140 were from four unpublished trials. DATA EXTRACTION: Individual patient data were collected using a standardized form and double data entry. DATA SYNTHESIS: Using the fixed treatment effect model, we found that the effect of immunization, denoted as the relative live-birth ratio (RR), was greater by pooling summary data from published articles (RR, 1.29; 95% confidence interval [CI], 1.03 to 1.60) than by pooling all individual patient data from the same investigators (RR, 1.17; 95% CI, 0.97 to 1.37) or when individual patient data were pooled from four unpublished trials (RR, 1.01; 95% CI, 0.74 to 1.28). A similar diminishing treatment effect for the same comparisons was observed using the random treatment effect model (RR, 1.38; 95% CI, 0.89 to 1.87 using published summary data; RR, 1.18; 95% CI, 0.98 to 1.42 using individual patient data; RR, 1.01; 95% CI, 0.74 to 1.28 using unpublished trials). CONCLUSIONS: Meta-analytic results may differ depending on the use of various data sources: whether the source was from summary statistics in the literature, from individual patient data provided by trialists, or from unpublished trials.