This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Celiac disease (CD) is a major public health problem affecting 1% of the Denver population and associated with significant morbidity. CD is under-diagnosed due to its variable clinical manifestations and absence of comprehensive screening. Case identification is now possible by testing for circulating antibodies to tissue transglutaminase (TG). However, the natural history and spectrum of CD in childhood still has not been defined. CD provides an opportunity to evaluate the interplay between genetic, immunologic, and environmental factors in the development of an autoimmune disease. Genetic susceptibility to CD, restricted to HLA-DR3,DQ2 and DR4,DQ8 haplotypes, requires further evaluation as non-HLA loci may also be important. Although TG tests are highly accurate for detecting clinical CD, their properties when used in population screening need evaluation. With progress in auto-antibody measurement technology, the predictive value of screening programs needs to be improved for widespread screening programs to be considered. The proposed studies will use cohorts of children at risk for CD, many of whom already express TG, to further evaluate genetic, environmental, immunologic, and clinical aspects of CD. In addition, after the diagnosis, children will be followed to characterize the effect of treatment. This information will be key to developing screening and prevention strategies in the future.
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