Increased Density of Jejunal γδ ⁺ T Cells in Patients Having Normal Mucosa - Marker of Operative Autoimmune Mechanisms?

Abstract

Both from a clinical and a biological point of view, coeliac disease can be classified among the autoimmune diseases, or one could suspect autoimmune mechanisms to be operative in the disease. The aim of the present study was to find evidence for mucosal markers of coeliac disease latency in patients clinically suspected but on routine biopsy excluded for the disease. Monoclonal antibodies were used to stain jejunal intraepithelial lymphocytes and mucosal HLA-DR. Serum IgA-class reticulin autoantibodies were measured by an indirect immunofluorescence and gliadin antibodies by an enzyme-linked immunosorbent assay method. The DQA1*0501 and DQB1*0201 alleles were determined. Twenty-seven of 107 consecutive patients had coeliac disease. Altogether 39 of 79 (49%) children with normal jejunal mucosa had an increased density of intraepithelial gammadelta+ T cells (> or = 4.4 cells/mm). IgA-class reticulin autoantibodies were positive in 18 (23%) of the children excluded for coeliac disease. The antibody positivity was mostly seen in patients carrying the DQAI 0501 and DQB1*0201 alleles. Also, reticulin autoantibody-positive children having normal jejunal mucosal morphology had significantly higher densities of intraepithelial gammadelta+ T cells than antibody negative ones. On 1.5-4.5 year follow-up four out of 18 (22%) children primarily excluded for coeliac disease showed mucosal deterioration and coeliac disease. Many patients clinically suspected of coeliac disease but having normal jejunal mucosa show markers of coeliac disease latency which may be gluten-induced indicating autoimmune mechanisms to be operative in the gut.