HLA-DQ genotyping combined with serological markers for the diagnosis of celiac disease: is intestinal biopsy still mandatory?

OBJECTIVES: The aim of this study was to evaluate the value of HLA-DQ2/DQ8 allelic genotyping combined with serologic testing for the diagnosis of celiac disease (CD). PATIENTS AND METHODS: One hundred seventy children, who underwent jejunal biopsy for digestive symptoms or malnutrition, were tested for HLA-DQ2/DQ8 and serologic markers (tTG and/or anti-endomysial antibodies). Children were classified in 2 groups, according to jejunal histology: group 1, when partial or total villous atrophy was associated with an increased intraepithelial lymphocytosis suggesting CD, and group 2, when these histological criteria were absent. RESULTS: Eight children were excluded from the study because their intestinal histology was not informative; 82 children were classified in group 1 and 80 in group 2. Eighty-one of 82 children in group 1 were positive for HLA and serologic testing. The other child had negative HLA and serologic testing but marked villous atrophy, and further investigation showed an allergic disease. Among the 80 children in group 2, 53 were negative for both HLA and serologic testing, 22 were positive for HLA but negative for serologic testing, 2 were negative for HLA and positive for serologic testing, and 3 patients were positive for both HLA and serologic testing. The last 3 children were shown to have an autoimmune background and had probably a latent form of CD. The association of HLA-DQ2/DQ8 and serologic markers had a sensitivity of 98.8%, a specificity of 96.2%, a positive likelihood ratio of 26.3, and a negative likelihood ratio of 0.013. CONCLUSIONS: The association of positive HLA-DQ2/DQ8 and serologic testing has a high predictive value for CD. We suggest that symptomatic children with high titers of immunoglobulin (Ig)A tTG could be diagnosed as patients with CD without performing jejunal biopsy. In other children, HLA-DQ2/DQ8 could be useful to exclude the diagnosis of CD if negative. In cases of low IgA tTG titers or in patients with IgA deficiency, intestinal biopsy remains mandatory.