Enterovirus infections in young infants: are children still protected by maternal antibodies?

Enterovirus infections are frequent in childhood and may be involved in development of several chronic diseases including type 1 diabetes. Maternal antibodies have a protective effect in young infants. It has been proposed that this protection is now vanishing due to decreasing circulation of enteroviruses in Western countries. We aimed to analyse the occurrence of enterovirus infections in 55 infants and to assess the protection provided by maternal antibodies to these children and the development of enterovirus antibodies in a prospective cohort study. In addition, the presence of enteroviruses was detected in faeces using RT-PCR and their serotype identified using VP1 region sequencing. Our results showed that before polio vaccination 12 of 194 faecal samples were positive for enterovirus RNA (coxsackieviruses A4, A5, A16 or echoviruses 13 and 16). After vaccination Sabin 1, 2 and 3 poliovirus strains predominated in stool samples. From birth to 6 months of age polio IgG and IgA increased in most of children whereas the levels of other enterovirus antibodies started to increase from 6 months to 24 months age. The frequency of maternal neutralizing antibodies was generally quite high but still 3 out of 8 infants had no maternal antibodies against the enterovirus serotype which they had in stool sample. This study shows that enterovirus infections are relatively frequent already before the age of 3 months. Considerable proportion of infants lack maternal antibodies against the virus causing their infection. The significance of this phenomenon needs to be evaluated in larger studies.

Demonstration of high prevalence of SS-A antibodies in a general population: association with HLA-DR and enterovirus antibodies.

Autoantibodies are helpful markers for diagnosing autoimmune diseases and there is a link between HLA-DR3 and the prevalence of SS-A antibodies in clinical groups. We aimed to study this association at the level of general adult population and to verify whether these antibodies are more common in persons with antibodies against enteroviruses as possible associates of Sjögren syndrome. The studied material included sera from 200 persons, randomly selected from a general population sample. The IgG type of SS-A/SS-B autoantibodies were measured by nuclear immunoblot, developed by us, and the results were compared to other results obtained by anti-SS-A immunoblot and ELISA. Enterovirus antibodies were detected by ELISA using common enterovirus antigenic peptide KEVPALTAVETGAT. Altogether 33 out of 200 sera showed SS-A and/or SS-B bands in immunoblot, including all seven ANA Profile 3 (Euroimmune) positive sera. One of the persons positive in these two tests showed also positive reaction on anti-SS-A ELISA (Euroimmune). None of the antibody-positive persons had Sjögren's syndrome or other rheumatic disease. Among 82 HLA typed persons, selected at random, the HLA-DRB1*03 and HLA-DRB1*11 allele carriers included significantly more persons with SS-A antibodies than the non-carries (p = 0.008). Antibodies against enterovirus peptide were present more frequently in persons with SS-A autoantibodies than in age- and sex-matched controls (p = 0.009). Summing up, our study showed that the prevalence of SS-A/SS-B antibodies in a general random population might be higher than thought previously being detected in up to 16.5% of persons including a significant number of those with HLA-DR3 or/and DR11 alleles and with antibodies against enteroviruses. Whether all these persons have the risk of developing rheumatic diseases should be evaluated by follow up studies.

Higher FoxP3 mRNA expression in peripheral blood mononuclear cells of GAD65 or IA-2 autoantibody-positive compared with autoantibody-negative persons.

The role of regulatory T cells (Tregs) in type 1 diabetes has been studied extensively. The most prevalent way to define Tregs has been by their surface expression of CD4 and CD25. As currently the transcription factor FoxP3 and the low expression of CD127 are regarded to be the most specific markers of Tregs, we analysed the number of Tregs defined by these molecules in peripheral blood mononuclear cells of diabetic patients and healthy controls. The gene expression of transforming growth factor beta and two isoforms of FoxP3 was measured as well. There were no significant differences between diabetic patients and healthy controls regarding the number of Tregs, or the expression of FoxP3 isoforms and TGFbeta in peripheral blood mononuclear cells. However, we found significantly higher expression of both full-length and Delta2FoxP3 in study subjects, positive for either GAD65 or IA-2 autoantibodies. The ratio of the expression of different isoforms was not changed. This study shows the possible role of FoxP3 in the development of tissue characteristic humoral immunity in type 1 diabetes.

Putative predictors of antibodies against follicle-stimulating hormone in female infertility: a study based on in vitro fertilization patients.

PROBLEM: We have previously demonstrated the presence of naturally occurring antibodies against follicle-stimulating hormone (FSH) in patients with endometriosis and polycystic ovary syndrome (PCOS). Here, we investigated the parameters associated with anti-FSH antibodies in in vitro fertilization (IVF) patients. METHODS OF STUDY: The following parameters were studied in 135 patients: peripheral FSH levels, FSH beta-subunit gene (FSHB) haplotypes, history of previous IVF, and susceptibility to autoimmune reactions in general [seven common autoantibodies (against nuclear antigens on human and rodent substrates, smooth muscle, gastric parietal cells, beta2-glycoprotein I, cardiolipin, and thyroid peroxidase) and HLA-DQB1 alleles]. RESULTS: Although the anti-FSH levels were higher in patients when compared with controls, those higher levels were not associated with FSHB haplotypes. The anti-FSH IgM associated with (i) the levels of FSH in women with male and tubal factor infertility; (ii) the history of IVF in patients with PCOS, endometriosis, and unexplained infertility; and (iii) the production of common autoantibodies among all IVF patients. The anti-FSH IgA associated with HLA-DQB1*03. The anti-FSH IgG correlated with the values of anti-FSH IgA and IgM. CONCLUSION: Anti-FSH may be naturally occurring antibodies associated with peripheral FSH concentrations, but increased in infertile women with dysregulation of immune reactions and repeatedly performed IVF.