Small-Bowel Mucosal Inflammation in Reticulin or Gliadin Antibody-Positive Patients without Villous Atrophy

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Abstract
We investigated whether individuals with positive coeliac disease antibodies but without small-bowel villous atrophy have mucosal inflammation implicating gluten-sensitivity. Small-bowel mucosal morphology; CD3+, alphabeta+, and gammadelta+ T-cell receptor-bearing intraepithelial lymphocytes; and mucosal HLA-DR expression were studied in 96 IgA-class antireticulin or antigliadin antibody-positive adults suspected of having coeliac disease and in 27 control subjects. Villous atrophy compatible with coeliac disease was found in altogether 29 patients, in 18 of 21 (86%) patients with both antireticulin and antigliadin antibodies, in 9 of 15 (60%) patients with antireticulin antibodies only, and in 2 of 60 (3%) with antigliadin antibodies only. In 67 antibody-positive patients with normal villous architecture the densities of CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes were significantly higher than in non-coeliac control subjects. Ten patients with initially increased densities of gammadelta+ T cells but normal villous structure underwent a follow-up biopsy after 4-18 months, which showed villous atrophy in five patients. IgA-class antireticulin or antigliadin antibody-positive patients with normal small-bowel mucosal morphology frequently have immunohistochemical markers of coeliac disease latency. Together with our follow-up data this implies that they may be gluten-sensitive.