Food allergy, coeliac disease and chronic inflammatory bowel disease in man

Abstract

It is often stated that the gastrointestinal tract has a limited number of responses to pathogens. Entirely different agents can produce a similar histopathological reaction. However, the expression of the disease in man is very heterogeneous, it varies with the age of the subject and is to a certain extent genetically determined. For example, food allergy is frequent in childhood and not common in adulthood. The intestinal mucosa in the child with cows milk allergy shows a 'flat' mucosa, which may be indistinguishable of that observed in gluten sensitive enteropathy or coeliac disease. Subjects with other forms of food allergy may have a morphologically normal small intestinal mucosa, occasionally with increased IgE plasma cells and often only characterised by an increased intestinal permeability. An abnormal intestinal permeability is one of the hallmarks of an inflamed gut, however, subjects with a latent form of coeliac disease have an abnormal permeability only without overt signs of inflammation. Recently, it has become clear that what determines the characteristics of the intestinal inflammatory response is dependent on the cytokines involved during the response and this seems to be the same in the stomach, the small intestine and the colon. A so-called Th1 response, with an increased production of IFN-gamma, TNF-alpha and other pro-inflammatory cytokines, occurs in the stomach when infected by Helicobacter pylori, in the small intestine when the subject with coeliac disease consumes normal bread and during the active phases of Crohn's disease. A Th2 response is characteristic of the allergic subject and there is some evidence that it is the predominant response in subjects with ulcerative colitis. We still do not know the fine-tuning of the cytokine response but IL-12 appears to be a key cytokine in polarising the response to a Th1 type. More recently it has become clear that the intestinal mucosa has a unique subset of CD4+ T cells that secrete TGF-beta (Th3 cells) that provide help for IgA. These cells have downregulatory properties for Th1 cells and therefore play an important role in the active suppression of oral tolerance and IgE response. What determines that an individual develops one of these diseases? It is now clear that these different pathological entities are multifactorial. Different environmental factors and a complex genetic predisposition where more that one gene and more than one chromosome are involved. The extent and severity of the inflammatory response depends on the genetic diversity of the bacteria or the amount of the antigen on the one hand and on the genetic constitution of the host on the other. The abnormal immune response in the human gut is predominantly a Th1-like inflammatory response. This can be elicited by bacteria, peptides, possibly the bacterial flora and some viruses. The recent findings in the pathogenesis of the intestinal inflammatory response will probably alter the therapy of the future.