Update on immunologic basis of celiac disease.
During the past few years several seminal studies have greatly expanded our knowledge on celiac disease pathogenesis. This review focuses on aspects that have been most properly addressed and where substantial new information has been gathered include. Topics covered include (a) the identification of T-cell epitopes in gluten and the mechanisms of specific T-cell response in celiac disease small intestine; (b) the mechanisms of induction of mucosal lesion; and (c) the putative role of non-T-cell factors in driving mucosal response to gliadin. After discussing a brief history of the "quest for the cause of celiac disease," we examine the development of the typical celiac lesion (the crypt hyperplastic mucosal atrophy) as it generally unfolds: the increased entry of dietary antigens; the early changes, linked to specific components of the innate immunity rather than to its adaptive branch; the most thoroughly investigated subsequent response, involving a strong T-cell response and cytokines; and the factors responsible for enterocytes' death. The emerging pattern is that of a complex interaction of factors, although far from being completely understood, but fascinating as it opens an incredible window of knowledge on an autoimmune disorder whose environmental factor is known, whose autoantigen is known, whose autoantibodies are known: a truly unique situation in medicine.
Guandalini
Stefano
S
University of Chicago, Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Chicago, Illinois 60637, USA. sguandal@peds.bsd.uchicago.edu
Gokhale
Ranjana
R