Summary. Background: Diagnosis of the antiphospholipid syndrome (APS) is difficult as a result of limited specificity of existing assays for detecting clinically relevant antiphospholipid antibodies. Anti-beta2-glycoprotein I (beta2GPI) antibodies play a central role in the disease process of APS. Objectives: We have investigated the relation between antiphospholipid antibodies with specificity for domain I of beta2GPI and thrombosis/pregnancy morbidity in an international multicenter study. Patients/methods: Four hundred and seventy-seven patients derived from nine different centres met the inclusion criterion of having anti-beta2GPI antibodies in their plasma/ serum. Clinical data and results of tests for lupus anticoagulant, anti-cardiolipin antibodies and anti-beta2GPI antibodies were established at the different centres of inclusion. After being retested for the presence of IgG and/or IgM anti-beta2GPI antibodies, the samples were tested for the presence of IgG-directed against domain I of beta2GPI and results were correlated with the thrombotic and obstetric history. Results: Re-testing for the presence of anti-beta2GPI antibodies resulted in inclusion of 442/477 patients. IgG class anti-domain I antibodies were present in plasma of 243/442 patients (55%).201/243 (83%) had a history of thrombosis. This resulted in an odds ratio of 3.5 (2.3-5.4, 95% confidence interval) for thrombosis. Anti-domain I IgG antibodies were also significantly correlated with obstetric complications [odds ratio: 2.4 (1.4-4.3, 95% confidence interval)]. Conclusion: In this multicenter study, the detection of IgG antibodies that are directed against domain I of beta2GPI proved to be more strongly associated with thrombosis and obstetric complications than those detected using the standard anti-beta2GPI antibody assay.
SummaryPolycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age. Free radicals, as a product of oxidative stress, impair cells and tissue properties related to human fertility. These free radicals, together with the oxidized molecules, may have a cytotoxic or deleterious effects on sperm and oocytes, on early embryo development or on the endometrium. Aldehyde-modified proteins are highly immunogenic and circulating autoantibodies to new epitopes, such as malondialdehyde (MDA), may affect the reproductive system. Autoantibodies or elevated reactive oxygen species (ROS) in serum are often associated with inflammatory response. The purpose of this work is to investigate whether PCOS women show increased levels of oxidized proteins (protein-MDA) and anti-endometrial antibodies (AEA) in their sera, compared with control patients, and to determine whether AEA specificity is related to oxidized protein derivatives. Sera from 31 women [10 patients with PCOS (PCOS group) and 21 women with male factor of infertility (control group)] were chosen from patients attending for infertility. Anti-endometrial antibodies were determined by enzyme-linked immunosorbent assay (ELISA) with an endometrial cell line (RL-95). Antibodies against MDA modified human serum albumin (HSA-MDA) were also determined by ELISA. Oxidized proteins (protein-MDA) in serum were determined by a colorimetric assay. Patients with PCOS have significantly higher levels of AEA and anti-HSA-MDA, as well as oxidized proteins (protein-MDA) in serum than control patients. For the first time, we describe an autoimmune response in PCOS patients, in terms of AEA. The evidence of protein-MDA in the serum of these patients, together with the increased antibody reactivity to MDA-modified proteins (HSA-MDA) in vitro , supports the conclusion that oxidative stress may be one of the important causes for abnormal endometrial environment with poor embryo receptivity in PCOS patients.
Immunologic cause of male infertility is a very important risk factor in the pathogenesis of sperm cells. Sperm autoantibodies and the presence of intra-acrosomal factors must be studied together, cytokines according to accessory cellularity in the semen.
The prevalence of celiac disease (CD) was determined in healthy blood donors and in high-risk groups of adults (a total of 1835 adults--randomly selected 1312 healthy blood donors, 102 patients with primary osteoporosis, 58 patients with autoimmune diseases and 365 infertile women). It was calculated on the basis of a two-step serologic screening method--in the first step IgA and IgG antigliadin antibodies (AGA) and IgA anti-gamma-glutamyltransferase ('transglutaminase') antibodies (ATG) were estimated, in the second step sera positive for IgA AGA and/or IgA ATG were examined for antiendomysial IgA (AEA) antibodies. Immunoenzymic assay (ELISA) was used for determining of AGA and ATG antibodies; immunofluorescence method, performed on human umbilical cord tissue, was used for assaying of AEA antibodies. Total serum IgA level in only IgG AGA positive subjects was measured by routine turbidimetric method. 0.45% of healthy blood donors, 0.98% of osteoporotic patients, 2.7% of patients suffering from autoimmune disease and 1.13% of women with infertility considered as immunologically mediated were found to be positive in both steps of serologic screening (AGA and/or ATG and antiendomysium positive). The presumed high prevalence of seropositivity for CD in apparently healthy Czech adult population was confirmed. In the high-risk groups, the prevalence of seropositivity for CD was approximately 2-4 times higher than in healthy blood donors. The real prevalence of CD in the tested groups, however, can be estimated after performing small intestinal biopsy in the seropositive patients.
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