Natural history of transglutaminase autoantibodies and mucosal changes in children carrying HLA-conferred celiac disease susceptibility.

Objective: The natural history of the appearance and fate of transglutaminase autoantibodies (TGAs) and mucosal changes in children carrying HLA-conferred celiac disease (CD) risk remains obscure. The aim of this study was to investigate the sequence of events leading to overt CD by retrospective analysis of TGA values in serum samples collected frequently from genetically susceptible children since birth or early childhood.

Material And Methods: A total of 1101 at-risk children were recruited in the study.

A six-fold gradient in the incidence of type 1 diabetes at the eastern border of Finland.

Objective: Type 1 diabetes results from gene-environment interactions in subjects with genetic susceptibility to the disease. We assessed the contribution of environmental and genetic factors to type 1 diabetes by comparing the incidence in two neighboring populations living in conspicuously different socioeconomic circumstances.

Research Design And Methods: We compared the incidence over a 10-year period (1990-99) in children younger than 15 years of age living in the Karelian Republic of Russia and in Finland.

Intrauterine exposure to maternal enterovirus infection as a risk factor for development of autoimmune thyroiditis during childhood and adolescence.

Maternal intrauterine enterovirus infection during pregnancy increases the risk for the offspring to develop type 1 diabetes mellitus. Type 1 diabetes mellitus and autoimmune thyroiditits (AIT) are closely linked. A common pathogenetic factor is possible.

Relationship between the incidence of type 1 diabetes and enterovirus infections in different European populations: results from the EPIVIR project.

The incidence of type 1 diabetes varies markedly between countries. As enterovirus infections have been linked to type 1 diabetes, we determined whether this variation correlates with the frequency of enterovirus infections in different Caucasian populations in Europe. Enterovirus antibodies were examined in the background population (1-year-old and 10-14-year-old children) in seven countries with either exceptionally high (Finland and Sweden) or low/intermediate incidence of diabetes (Estonia, Germany, Hungary, Lithuania, Russia) using EIA and neutralisation assays.

Epitopes recognized by CBV4 responding T cells: effect of type 1 diabetes and associated HLA-DR-DQ haplotypes.

The present study aimed at characterizing the epitopes recognized by coxsackievirus B4 (CBV4)-specific T-cell lines established from 23 children with type 1 diabetes (T1D) and 29 healthy children with T1D risk-associated HLA genotypes. Responsiveness to VP1 region was dependent on the specific infection history as 55% of the T-cell lines from donors with neutralizing antibodies to CBV serotypes responded to VP1 peptides compared to none of the T-cell lines from other donors (P = 0.01).

Real-time PCR for rapid diagnosis of entero- and rhinovirus infections using LightCycler.

Background: PCR techniques have proved to be more sensitive than traditional cell culture in the diagnosis of enterovirus and rhinovirus infections and are widely used in clinical virus laboratories. However, PCR assays are relatively time-consuming and labor intensive, particularly if separate hybridization steps are used to confirm the specificity of positive findings.

Objectives: The aim of the present study was to develop fast and sensitive real-time PCR assay, which would allow simultaneous detection of entero- and rhinoviruses and their quantification in clinical and experimental samples.

Can enteroviruses cause type 1 diabetes?

Enterovirus infections have long been considered as one possible environmental trigger of type 1 diabetes. These viruses have been detected from diabetic patients more often than from control subjects and they can infect beta cells in cell culture and induce diabetes in animal models. Furthermore, a same kind of seasonality has been observed in both the onset of clinical diabetes and subclinical beta cell autoimmunity (appearance of autoantibodies) as in enterovirus infections.

Enterovirus infection during pregnancy is not a risk factor for celiac disease in the offspring.

Background: There is a strong genetic influence on the susceptibility to celiac disease but it is also evident that environmental factors play a role in the development of the disease. Diverging studies about adenovirus infection as a possible triggering factor in the pathogenesis have been reported. Our study was undertaken to determine whether enterovirus infection during pregnancy is a risk factor for the development of celiac disease later in childhood.

Enterovirus infections are associated with the induction of beta-cell autoimmunity in a prospective birth cohort study.

Enterovirus infections have been associated with the manifestation of clinical type 1 diabetes in a number of reports, and recent prospective studies have suggested that enterovirus infections may initiate the autoimmune process, leading to the disease. In the present study, we analyzed the role of enterovirus infections in a Finnish birth cohort study, Diabetes Prediction and Prevention (DIPP), in which all newborn infants are screened for diabetes-associated HLA-DQB1 alleles, and those with an increased genetic risk are invited for prospective follow-up. Enterovirus infections were diagnosed by serology and reverse transcriptase-polymerase chain reaction (RT-PCR) from serum samples taken from birth every 3-6 months.

Enterovirus infections and type 1 diabetes.

Type 1 (insulin-dependent) diabetes is a typical organ-specific autoimmune disease where insulin-producing beta cells are destroyed by immune mediated mechanisms. The risk of the disease is modulated by genetic factors, mainly genes coding for human leukocyte antigens (HLA), but environmental factors are needed to trigger the process in genetically susceptible individuals. Possible viral triggers of the disease have been sought for years but their identification has been very difficult.

Maternal first-trimester enterovirus infection and future risk of type 1 diabetes in the exposed fetus.

Previous studies have suggested that enterovirus infections during pregnancy may increase the risk of type 1 diabetes in the offspring. Our aim was to evaluate the role of first trimester enterovirus infections in a larger cohort of pregnant women. Two series of pregnant women were analyzed as follows: 948 women (series 1) and 680 women (series 2) whose child developed clinical diabetes before the ages of 15 or 7 years, respectively.

Environmental factors in the etiology of type 1 diabetes.

Type 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes.

T cell epitopes in coxsackievirus B4 structural proteins concentrate in regions conserved between enteroviruses.

The present study aimed to characterize systematically the target epitopes of T cell responses in CBV4 structural proteins. These were studied by synthesizing 86 overlapping 20-aa-long peptides covering the known sequence of CBV4 structural proteins and analyzing the proliferation responses of 18 CBV4-specific T cell lines against these peptides. Recognized peptides differed depending on the HLA-DR genotype of the T cell donor.