Abnormalities in CD57+ cytotoxic T cells and Vδ1+ γδT cells in subclinical celiac disease in childhood are affected by cytomegalovirus. The Generation R Study.

Celiac disease (CD) is a digestive and autoimmune disorder driven by an immune response to modified gluten peptides. Affected intestines show infiltrates of various T-cell and NK-cell subsets. It is currently unclear if individuals with subclinical CD have systemic abnormalities in immune cells. We here studied whether subclinical CD is associated with changes in blood CD57-expressing and Vδ1-expressing lymphocytes in children, and whether cytomegalovirus (CMV) infection modifies this association. Included were 1068 children from the Generation R Study. Serum Immunoglobulin G (IgG) levels against CMV were measured by ELISA; Tissue transglutaminase type 2 antibody (TG2A) levels with fluorescence enzyme immunoassay (FEIA). Duodenal biopsies, additional Human Leukocyte Antigen (HLA) DQ 2.2, 2.5 and 8 and endomysial antibody (EMA) typing were performed in TG2A positive children. Subclinical CD cases (n=12) had 1.8 fold (95% CI 1.06; 3.1) fewer Vδ1+ T cells which was predominantly observed in CMV seronegative children (p-interaction 0.02), and 2.7 fold (95% CI 1.25; 5.99) more CD57+ T cells than HLA DQ2/-DQ8 positive controls (n=339). Hence, children with subclinical CD have alterations in specific blood T cell subsets that are linked to viral pathology. The observed interaction effect between subclinical CD and CMV may contribute to the understanding of disease pathogenesis.