Autoimmune enteropathy with distinct mucosal features in T-cell activationdeficiency: The contribution of T cells to the mucosal lesion

Background: Autoimmune enteropathy is normally characterised by crypt hyper plastic villous atrophy with enterocyte autoantibodies, activation of mucos al lymphocytes and increased epithelial HLA-DR. This case involved a severe ly affected Portuguese infant who was found to have lymphocyte activation d eficiency and demonstrated correspondingly distinct mucosal features. Methods: A female infant of nonconsanguineous parents was treated for vomit ing and diarrhoea, first with milk exclusion and then with parenteral nutri tion. Lymphocyte subsets and immunoglobulin concentrations were normal, but in vitro testing showed no activation in response to phytohaemagglutinin, Candida, or purified protein derivative, although the response to interleuk in (IL)-2 was intact. Interleukin-2 deficiency was excluded. Analysis of je junal biopsy specimens revealed only mild villous blunting with absent gobl et cells, normal epithelial proliferation, and no crypt hyperplasia. The de nse infiltrate of CD8(+) and CD4(+) T lymphocytes showed normal CD2 and CD3 expression but no activation or proliferation markers, HLA-DR was not incr eased on epithelium or lymphocytes. Thus, in addition to in vitro evidence for lymphocyte activation deficiency, the mucosal specimens showed no evide nce of in situ T-cell activation. Results: After development of overwhelming septicaemia, the patient died at 18 months, just before a planned bone marrow transplant. Conclusions: These findings confirm significant heterogeneity within autoim mune enteropathy. Formal immune function testing should be performed in all affected infants to identify T-cell activation deficiencies. The distinct mucosal findings suggest that activated T cells usually induce the crypt hy perplastic villous atrophy characteristic of classic autoimmune enteropathy .