Comparison of frequencies of antibodies against tissue transglutaminase and HLA haplotypes, associated with celiac disease among Lithuanian children with type 1 diabetes mellitus and healthy controls.

Type 1 diabetes (T1D) is caused by the irreversible loss of pancreatic β cell function. Dysfunction of glucose metabolism and subsequent hyperglycemia results from the lack of insulin, which is produced by β cells. Celiac disease is a chronic disorder of the small intestine. It is characterized by damage to the intestinal mucosa and intestinal malabsorption, which is caused by the wheat protein gluten or similar proteins from barley or rye. T1D and celiac disease are autoimmune disorders that are linked together by common genetic (e.g. human leukocyte antigen (HLA) haplotypes DQ2 and DQ8), environmental (e.g. dietary gluten) risk factors, similarities in pathogeneses and a tendency to occur together. Incidence rates of T1D and celiac disease vary greatly between countries. However a growing tendency is evident. Between 1 and 16 percent of patients with T1D also develop celiac disease. Therefore it is imperative that the links between the two diseases are investigated. Our aim was to determine the frequencies of celiac disease associated HLA haplotypes and occurrence of antibodies against tissue transglutaminase (TTG) among children with T1D and healthy children and to evaluate the link between these biomarkers and T1D. The tasks set to reach our aim were: to determine the frequencies of celiac disease associated HLA haplotypes, to determine the frequencies of antibodies against TTG and to evaluate the associations between antibodies against TTG and HLA haplotypes. This study was a continuation of the case-control study “Effects of environmental factors on the incidence of T1D in children”. 271 children with T1D and 289 healthy children from the Lithuanian population were tested. HLA genotyping was performed by polymerase chain reaction using sequence specific oligonucleotides and primers. IgG class antibodies against TTG were detected by radioimmunoassay. We found that 41.5 percent of children with T1D had the DR3-DQ2 haplotype, compared with 7.0 percent of healthy children. The frequency of DR4-DQ8 among children with T1D was 54.9 percent, compared with an 11.3 percent frequency among healthy children. 11.1 percent of children with T1D also had antibodies against TTG, while only 1.4 percent of healthy children had antibodies against TTG. We determined that the DR3-DQ2 haplotype increased the risk of developing antibodies against TTG by almost 124 times for healthy children, but not children with T1D. Our conclusions: children with T1D more frequently than healthy children had DR3-DQ2 and DR4-DQ8 celiac disease associated haplotypes, while healthy children more frequently had the DQ7 haplotype. Antibodies against TTG were detected more frequently and at higher titers in children with T1D than healthy children. HLA DR3-DQ2 haplotype increased the risk of developing antibodies against TTG for healthy children. Celiac disease and T1D are linked by similar pathogeneses. They share many genetic and environmental risk factors, therefore the diseases often coincide. Due to this link it is beneficial to monitor and periodically perform screening assays for children afflicted by one of these illnesses