Celiac Disease - NIH Consensus Development Program - National ...

There are populations at particularly high risk of developing celiac disease, includingindividuals with multiple different autoimmune disorders and with type 1A diabetes. Figure 1(from barbaradaviscenter.org Web book on immunology of diabetes) illustrates the risk ofexpression of transglutaminase autoantibodies (TGA) amongst patients and their relatives withtype 1A diabetes subdivided by DR3 haplotypes containing DQ2.25% ID D M20%RelativesP opulation15%10%5%0%DR3+DR3­BDCFigure 1. Prevalence of TGA by HLA-DR Amongst Patients WithType 1 Diabetes Mellitus, Relatives of Patients with DiabetesMellitus, and the General PopulationOf newborns evaluated in the DAISY study, headed by Marian Rewers of the BarbaraDavis Center, 39.5 percent have either DQ2 and/or DQ8. At present, this is the primary geneticlocus that can be relied upon for determining risk at birth. Individuals not expressing DQ2 orDQ8 are at low risk. These same two alleles determine risk for type 1A diabetes and Addison’sdisease but their negative predictive values (ability with celiac disease to “exclude” 60 percent ofpopulation) are lower. It is a difficult task to ascertain additional loci determining celiac diseasegiven the development of complications such as intestinal T-cell lymphoma. At present onlyMHC alleles can be considered for genetic analysis.Given the ability to define a higher- and lower-risk group with relatively simple class IIHLA typing, an important question is whether therapy would need to be instituted in earlyinfancy. Prospective epidemiologic questions, in particular studies of diet headed by Jill Norrisof the CEDAR study, are evaluating whether timing of introduction of, for instance, gliadin willinfluence the eventual development of celiac disease. If such a dietary influence is found and hasa life-long benefit, it would be a major impetus for newborn screening.38