Celiac sprue is primarily a disease of blocked cellular recognition

A key initial event is proposed for the pathogenesis of celiac sprue. The indigestible fragments generated from gluten are actively transported to the vicinity of sites which are critical for recognition of intestinal basement membrane by enterocytes. The fragments are attached in the vicinity of those sites by transamidation and make the recognition sites unavailable. Enterocytes are lost because they do not recognize that they are in the right place. Proliferation in the crypts of Lieberkühn and immune reactions in the epithelium are normal and appropriate. This hypothesis is shown to be compatible with a variety of observations, some of which are difficult to explain otherwise. Absence of a good animal model is laid to the sensitive site being a human peculiarity. The pattern of damage and the fact of recovery on a gluten-free diet are explained since the immune reactions and tissue remodeling observed are normal responses to tissue damage.