Is endometriosis an autoimmune disease?
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Autoimmune Diseases↗
Biomedical subjects
N S Rote
Publications and source records attributed to N S Rote.
Association of lupus anticoagulant with antibody against phosphatidylserine.
Lupus anticoagulant (LAC) is an antiphospholipid autoantibody identified by prolongation of in vitro phospholipid-dependent coagulation tests. Its presence is associated with thromboembolic disease and recurrent pregnancy loss in patients with or without clinical autoimmune disease. The purpose of this study was to identify the specific phospholipid(s) against which LAC is directed. The sera of 15 patients with LAC and of 41 LAC-negative controls were evaluated. Specific phospholipids were used to inhibit IgG binding in a partial thromboplastin ELISA, and serologic reactivity was measured with ELISAs which used specific phospholipids in the solid phase. Both phosphatidylserine and cardiolipin significantly inhibited IgG binding in the partial thromboplastin ELISA (76 and 75%, respectively); however, the serum of one patient who was strongly positive for LAC in coagulation assays was not inhibited by cardiolipin. In the specific phospholipid ELISAs, LAC-positive sera contained IgG (15 of 15 sera) and frequently IgM (9 of 15 sera; 60%) to phosphatidylserine. Most LAC-positive sera also contained IgG antibodies against other phospholipids: cardiolipin (10 of 11 sera; 91%), phosphatidylcholine (1 of 15 sera; 7%), phosphatidylethanolamine (12 of 15 sera; 80%), phosphatidylglycerol (12 of 15 sera; 80%), and phosphatidylinositol (10 of 15 sera; 67%). None of the LAC-negative controls had measurable IgG against any of these phospholipids. We conclude that LAC-positive sera contain antibody specificities against multiple phospholipids; however, anticoagulant activity is always associated with the presence of antibodies against phosphatidylserine.
Abortion, Habitual↗
Platelet-binding immunoglobulins in pregnancy-induced hypertension. I. Platelet-associated IgM on fetal platelets: evidence of a fetal autoimmune reaction?
Pregnancy-induced hypertension (PIH) can be complicated by maternal or fetal thrombocytopenia, or both. In order to investigate possible immunologic causes of these thrombocytopenias, platelet-associated IgG (PAIgG) and IgM (PAIgM) were measured in mothers with PIH and in their infants and compared with those from patients with autoimmune thrombocytopenic purpura (ATP), a known immunodestructive platelet disorder. Many PIH patients (33.3%) and most ATP patients (68.1%) had elevated levels of maternal PAIgG. In both diseases, the amount of PAIgG was directly proportional with the degree of thrombocytopenia (r = 0.446 in PIH and r = 0.668 for ATP). But in neither disease did the degree of maternal thrombocytopenia correlate with the degree of neonatal thrombocytopenia (r = 0.153 for PIH and r = 0.175 for ATP). Umbilical cord samples from PIH patients contained PAIgG (53.3%) and PAIgM (53.8%), whereas the umbilical cord samples from ATP patients had elevated amounts of PAIgG but not PAIgM. PAIgM in the umbilical cord blood could not be accounted for by IgM rheumatoid factors, IgM-containing immune complexes, or non-specific adsorption because of elevated total IgM levels. The umbilical cord blood PAIgM was probably not of maternal origin because it was observed even when the maternal blood contained no PAIgM and maternal IgM is not normally transported transplacentally. Therefore, the PAIgM appears to be of fetal origin. These results suggest that both maternal and fetal immunologic mechanisms may be involved in PIH-induced thrombocytopenia; if so, this is one of the first reported examples of a possible fetal autoimmune response.
Autoantibodies↗
Platelet-binding immunoglobulins in pregnancy-induced hypertension. II. Origin of circulating IgG and IgM antiplatelet antibodies in the umbilical cord serum.
IgG and IgM have been identified on the surface of maternal platelets in both autoimmune thrombocytopenia (ATP) and pregnancy-induced hypertension (PIH). IgG is also found on the umbilical cord platelets of patients with ATP and PIH, whereas IgM is only found on the umbilical cord platelets of patients with PIH. The possible maternal or fetal origins of these umbilical cord blood immunoglobulins were investigated by immunoblot analysis of antibodies in paired maternal and umbilical cord blood sera of ATP and PIH patients. Maternal sera contained IgG and IgM antibodies which reacted with several platelet proteins, however, a large amount of patient-to-patient variation was observed in the specific antigens that were identified. Analysis of paired maternal and umbilical cord sera from patients with ATP or PIH showed identical patterns of antigen specificity, which suggested that the IgG antibodies in the fetal circulation were of maternal origin. Circulating IgM antibodies were not observed in the umbilical cord sera of ATP patients. The umbilical cord sera of PIH patients, however, contained IgM antibodies that reacted against a variety of platelet antigens. In addition, most umbilical cord sera from PIH patients had identical patterns and relative intensities of reactivity, which differed from the patterns observed in the paired maternal sera. Antiplatelet IgM in the umbilical cord blood of PIH patients, therefore, appears to be a product of the fetal immune system.
Autoantibodies↗
A new postpartum syndrome associated with antiphospholipid antibodies.
Three women with antiphospholipid antibodies and a postpartum syndrome of pleuropulmonary disease, fever, and cardiac manifestations are presented. Each patient had either lupus anticoagulant or anticardiolipin antibodies or both, but did not have antinuclear antibodies or fulfill the criteria for the diagnosis of systemic lupus erythematosus. No infection or embolus was detected that could explain the pulmonary findings. All three patients had electrocardiographic abnormalities, and one patient developed a cardiomyopathy with extensive immunoglobulin G (IgG), IgM, IgA, and C3 deposition in the myocardium. In addition to the reported association between antiphospholipid antibodies and fetal loss, fetal growth retardation, and preeclampsia, we suggest that patients with antiphospholipid antibodies are at risk for a previously unreported and serious autoimmune postpartum syndrome.
Adult↗
Immunologic aspects of recurrent abortion and fetal death.
Although mechanisms that prevent rejection of the conceptus are incompletely understood, recent evidence suggests that maternal immunologic aberrations may cause repeated abortions. Autoimmune conditions associated with antiphospholipid antibodies sometimes produce vascular abnormalities in the decidua and placenta; successful pregnancies can be achieved in most of these women by treatment with corticosteroids and low-dose aspirin. Abnormal maternal immune responses to paternal or trophoblast alloantigens, with insufficient production of blocking antibodies or suppressor cells, have also been implicated. Immunization of these patients with paternal or third-party leukocytes has resulted in a number of live births. However, the mechanism of action, effectiveness, and safety of all treatment regimens remain controversial. Present recommendations for the evaluation of recurrent-abortion patients include diagnosis and appropriate treatment of traditional nonimmunologic and more recently recognized autoimmune factors. The remaining patients with no detectable cause for repetitive pregnancy loss are candidates for referral to research centers for further immunologic evaluation and experimental immunotherapy.
Abortion, Habitual↗
The demonstration of lupus anticoagulant by an enzyme-linked immunoadsorbent assay.
Lupus anticoagulant, an autoantibody associated with thromboembolic disease and pregnancy loss, is currently identified by its capability to prolong phospholipid-dependent coagulation tests, such as the activated partial thromboplastin time (APTT). The use of a coagulation assay for the detection of an antibody has several inherent disadvantages: fresh plasma is required for accurate testing, prolongation of coagulation test(s) is not specific for lupus anticoagulant, and coagulation assays are not easily manipulated for the characterization of antigen-antibody interactions. Using partial thromboplastin an the antigen, we have developed an enzyme-linked immunoadsorbent assay (ELISA) for the detection of lupus anticoagulant. Fifteen women with lupus anticoagulant (being evaluated for recurrent pregnancy loss or autoimmune disease) and 40 lupus anticoagulant-negative controls (including 20 with recurrent pregnancy loss, 12 parous women, and 8 with known autoimmune disease) were evaluated using the APTT and ELISA assays for lupus anticoagulant. All patients with lupus anticoagulant, as defined by the APTT, had significantly elevated IgG (sensitivity and specificity, 100%) or IgG + IgM (sensitivity 93%, specificity 95%) levels compared to controls.
Autoantibodies↗
Immunologic thrombocytopenic purpura.
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Adrenal Cortex Hormones↗
Methods of assessment and importance of opsonic activity for GBS.
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Animals↗
Monoclonal antibody preparations for immunotherapy of experimental GBS infection.
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Animals↗
Protective efficacy of hybridoma type-specific antibody against experimental infection with group-B Streptococcus.
Murine monoclonal antibodies to group-B Streptococcus type III were developed by fusion of splenic lymphocytes from immunized BALB/c mice with the mouse-myeloma cell line SP 2/0. The four type III-specific antibodies, which were of the IgM class, protected neonatal rats against intraperitoneal infection with homologous-type group-B streptococci; survival rates were 95%-100% for protected rats but only 17% for unprotected rats. One antibody preparation offered excellent protection against any of five type-III strains employed. Monoclonal antibody provided protection when administered 4, 8, or 12 hr after infection, although delayed administration was less efficacious against more virulent strains. Monoclonal IgM also protected against intranasal inoculation of bacteria. These results indicate the potential therapeutic efficacy of monoclonal antibody in neonatal group-B streptococcal disease, but further laboratory investigations must precede clinical investigation of monoclonal or polyclonal antibody therapy in humans.
Animals↗
Circulating immune complexes in pregnancy, preeclampsia, and autoimmune diseases: evaluation of Raji cell enzyme-linked immunosorbent assay and polyethylene glycol precipitation methods.
Sera from 86 individuals were tested for circulating immune complexes by the polyethylene glycol precipitation method and a Raji cell enzyme immunoassay (Raji-ELISA). These included normal nonpregnant control subjects, nonpregnant patients with autoimmune diseases, healthy women in the second and third trimesters of pregnancy, patients with preeclampsia, and women with pregnancies complicated by preexisting autoimmune diseases. Diseases such as systemic lupus erythematosus and rheumatoid arthritis were associated with increased levels of immune complexes in both pregnant and nonpregnant individuals. Circulating immune complexes were not observed in normal pregnancies or in preeclampsia. Although pregnancy itself is not an immune complex-associated state, the presence of immune complexes in autoimmune diseases may explain some of the complications observed during pregnancy in these patients.
Antigen-Antibody Complex↗
Antiplatelet antibodies and platelet counts in pregnancies complicated by autoimmune thrombocytopenic purpura.
In 48 pregnant women with autoimmune thrombocytopenic purpura, no consistent correlation was found between the infant platelet count and either the maternal platelet count, a previous maternal splenectomy, or maternal treatment with corticosteroids. Although the concentration of antiplatelet antibody in maternal serum frequently reflected the severity of neonatal thrombocytopenia, a number of exceptions to this observation limited the clinical usefulness of the test for individual patients. Antiplatelet antibody levels in the amniotic fluid were always low. A twin gestation in this series of patients in which one infant was thrombocytopenic and the other was not also showed that no antepartum maternal clinical characteristic or laboratory test can accurately predict the fetal platelet count. Only fetal platelet counts from scalp samples obtained prior to or early in labor from 25 patients with autoimmune thrombocytopenic purpura proved to be reliable in assessing the degree of fetal thrombocytopenia and selecting the appropriate route of delivery.
Adrenal Cortex Hormones↗
Detection of circulating immune complexes with a Raji cell enzyme immunoassay.
The Raji cell assay for circulating immune complexes (CIC) is frequently the method of choice when the detection of large, complement fixing complexes is desired. We have developed an enzyme-linked immunosorbent assay modification (Raji-ELISA) of the Raji cell technique which is easy to perform, uses commercially available reagents and is more convenient than the conventional Raji cell radioimmune assay (Raji-RIA). Fourteen samples were tested by both assays and a good correlation was observed (P = 0.05). Sera from patients with suspected immune complex associated diseases were tested in the Raji-ELISA. Unsensitized Raji cells gave a value of 1.25 micrograms of immune complex associated IgG/ml. Using 2 standard deviations as a cutoff to determine positivity, 2 of 32 healthy controls (6.2%) had elevated levels of circulating immune complexes. In our study population, 9 of 23 cancer patients (39.1%), 10 of 13 patients with autoimmune diseases (76.9%), 3 of 17 patients with positive rheumatoid factor titers (17.6%), 1 of 23 pregnant patients (4.3%), 1 of 5 preeclamptic patients (20%) and 9 of 30 other patients with suspected immune complex associated diseases (30%) had elevated levels of CIC.
Animals↗
Histocompatibility in couples with recurrent spontaneous abortion and normal fertility.
Histocompatibility between husband and wife at the HLA locus has been suggested as a determinant of recurrent spontaneous abortion. We measured the incidence of HLA antigen sharing within 12 couples with histories of unexplained recurrent abortion and in a fertile control population of 77 couples. In the recurrent abortion group, 6 of 12 (50%) of the couples shared no HLA antigens, whereas only 3 of 12 (25%) shared one antigen, 1 of 12 (8.3%) shared two antigens, and 2 of 12 (17%) shared three antigens. In the fertile group, 27 of 77 (35.1%) shared no antigens, 33 of 77 (42.8%) shared one antigen, 14 of 77 (18.2%) shared two antigens, 2 of 77 (2.6%) shared three antigens, and 1 of 77 (1.3%) shared four antigens. In 50 of these control couples who were available for complete reproductive histories, there were no significant correlations between the incidence of antigen sharing and the numbers of offspring, the incidence of spontaneous abortion, or infertility problems. Six of the women in the recurrent abortion group became pregnant during the study. Three of these (50%) delivered live infants independent of the degree of antigen sharing and without the benefit of immunologic treatment. Therefore, the degree of HLA antigen sharing did not define a population with increased pregnancy wastage or predict subsequent pregnancy outcome.
Abortion, Habitual↗
Assessment of the virulence factors of group B streptococci: correlation with sialic acid content.
Previous studies demonstrated strain-specific differences in opsonic requirements and virulence in neonatal rats among organisms of the same serotype of group B streptococci. The present study investigated the role of sialic acid cell-surface determinants in differences in virulence. Serotype III strains resistant to opsonization by antibody-containing sera had a higher percentage of cellular sialic acid than other organisms (1.02% sialic acid for four type III resistant strains versus 0.59% for three type III sensitive strains; P less than 0.01). Neuraminidase removed up to 70% of the extractable sialic acid from serotype III strains, markedly decreased their virulence, and made them more sensitive to the effects of protective antibody. No differences in sialic acid content were detected between sensitive and resistant strains of serotype II, and neuraminidase did not significantly remove sialic acid or affect their virulence. The present studies suggest differences in the nature or mode of attachment of virulence factors between types II and III of group B streptococci.
Antibodies, Bacterial↗
Studies by enzyme-linked immunosorbent assay (ELISA) of antiplatelet antibody and transient neonatal thrombocytopenic purpura.
Autoimmune thrombocytopenic purpura (ATP) is an antibody-mediated autoimmune disease of platelets. Transplacental passage of the antibody during pregnancy can result in transient neonatal thrombocytopenia, but it is not known why some infants of antibody-positive, thrombocytopenic mothers are not affected. We have developed a competitive enzyme-linked immunosorbent assay (ELISA) to measure circulating antiplatelet antibody and have used this technique to investigate the influence of maternal titers on the occurrence of neonatal thrombocytopenia. The assay is sensitive over a range of 12.5 to 800 ng of immunoglobulin G (IgG) per microtiter well and closely correlates with the complement lysis inhibition assay (CLIA) for antiplatelet antibody (correlation coefficient = 0.726). In many instances, the level of circulating antiplatelet antibody in maternal and cord bloods reflected the degree of maternal and neonatal thrombocytopenia, but several important exceptions were observed. We suggest that levels of antiplatelet antibody in the maternal blood and cord blood are not always predictive of the degree of neonatal thrombocytopenia.
Autoantibodies↗
A comparison of acid-elution techniques and alpha-fetoprotein levels for the detection of fetomaternal bleeding.
Practical and reliable methods to identify and/or quantitate fetal blood are becoming more important in the modern practice of obstetrics. In this study, two commercially available acid-elution techniques were compared with plasma -alpha-fetoprotein (AFP) by simultaneously testing samples of fetal blood mixed with adult blood in fixed ratios. Thirty-one samples representing a range of amounts of fetomaternal hemorrhage, from 0.024 to 48 ml, were analyzed. The acid-elution techniques were equally effective in detecting fetomaternal hemorrhage greater than 15 ml, but the bmc Reagent set was the most accurate for detection of small numbers of fetal erythrocytes. The accuracy of AFP was greater than that of either acid-elution technique, but its clinical usefulness is limited by the necessity for a prehemorrhage sample.
Female↗