Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease

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Abstract
Summary Background Reliable markers of early developing coeliac diseases are needed. Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of subsequent coeliac disease. Aim To investigate whether determination of intestinal transglutaminase 2-targeted autoantibody deposits would detect early developing coeliac disease better than previous methods. Methods The study investigated patients previously excluded for coeliac disease: 25 had positive serum coeliac autoantibodies (endomysial), 25 antibody-negative had Marsh I, and 25 antibody-negative had Marsh 0 finding. Seven (median) years after baseline investigation, new coeliac cases were recorded, and small bowel biopsy was offered to the rest of the patients. Serum and intestinal coeliac autoantibodies and intraepithelial lymphocytes were assessed as indicators of developing coeliac disease. Results Seventeen patients had developed coeliac disease: 13 in the autoantibody-positive group, three in the Marsh I group and one in the Marsh 0 group. At baseline, intestinal coeliac autoantibody deposits had a sensitivity and specificity of 93% and 93% in detecting subsequent coeliac disease, CD3+ 59% and 57%, γδ+ 76% and 60%, and villous tip intraepithelial lymphocytes 88% and 71%, respectively. Conclusions Endomysial antibodies with normal histology indicates early developing coeliac disease. Transglutaminase 2-targeted intestinal autoantibody deposits proved the best predictor of subsequent coeliac disease.