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Disturbances in intraepithelial lymphocyte homeostasis in coeliac disease may lead to the emergence of lymphoid malignancies
Enteropathy-type intestinal T cell lymphomas (EITCL) are a recognised complication of coeliac disease (CD).1 A recent survey confirmed that non-Hodgkin lymphomas, although rare, are the main cause of mortality in CD.2 The mechanisms favouring the development of EITCL in CD patients but not in other chronic inflammatory bowel diseases remain elusive, but mounting evidence points to a profound disturbance in intraepithelial lymphocyte (IEL) homeostasis, leading to the emergence of lymphoid malignancies. A link between IELs and EITCL was first advocated in 1988 by Spencer et al who observed that most EITCL expressed the CD103 IEL marker.3 Two complementary observations suggested that EITCL derive from a reactive T cell population present in the intestine of CD patients: thus the same T cell clonal rearrangement was detected by Murray et al in EITCL and in the adjacent non-tumoral flat mucosa,4 and by Ashton-Key et al in non-lymphomatous ulcers of ulcerative jejunitis and in lymphomas, which later developed in these patients.5 Recent work in refractory sprue (RS) provided a missing link between IELs and lymphomas in CD.
RS is a coeliac-like enteropathy, primary or secondary resistant to a strict gluten free diet (GFD). Several conditions underlie villous atrophy resistant to GFD6 (Cellier et al, …