Contribution of genetics to a new vision in the understanding of inflammatory bowel disease

Abstract

Inflammatory bowel diseases (IBD), such as Crohn' s d i s e a s e ( C D ) a n d u l c e ra t i v e c o l i t i s ( U C ) , a r e chronic inflammatory autoimmune conditions of the gastrointestinal tract. Other organs, such as the eyes, skin and articulations, are often affected and IBD may be accompanied by other diseases of autoimmune origin. There is no single etiological factor responsible for the onset of IBD. Recent advances in genetics and in the molecular mechanisms of the proteins coded by these genes have given rise to a new vision in understanding these complex diseases. Activation of specific genes that affect antigen presentation and the handling of cells by innate immunity may lead to autoimmunity with the consequent activation of the major histocompatibility complex (MHC) and multiple cytokines involved in the regulation of acquired immunity. In this review IBD is described as a constellation of diseases that can best be classified as barrier diseases. This vision, developed by Kiel in Germany, includes the idea that changes in our environment due to the westernization of civilization have not been met with adaptation of the innate immune system, and this has given rise to autoimmune diseases. These diseases affect 1-5 of 1000 individuals and represent a major burden on the national health systems of many countries on different continents. On a world scale, a major challenge is to generate interventions to prevent the development of these diseases in Asia, Latin America and Africa.

Differential susceptibility of P-glycoprotein deficient mice to colitis induction by environmental insults

“…Inflammatory bowel diseases (IBDs) are diseases of unknown etiology characterized by recurrent, spontaneous inflammation of the gastrointestinal tract (GI) 1. IBD consists of 2 disease phenotypes, ulcerative colitis (UC) and Crohn's disease (CD).…”

“…These diseases are proposed to be the result of genetic predispositions for either altered immune function leading to aberrant immune responses to natural stimuli, or overall autoimmune dysregulation 2. Studies show that 20% of patients with IBD have a relative with either UC or CD; in fact, a positive family history is thought to be the single greatest predictive factor associated with the disease 1, 3…”

“…Expression of genetic mutations may leave individuals predisposed toward colitis development in response to mitigating factors, such as a bacterial colonization or infection 1. We therefore hypothesized that the B6.…”

Linfocitos intraepiteliales y células dendríticas: Distribución y utilidad en el diagnóstico y en la modulación de la respuesta inmunitaria intestinal.

“…Aunque se ha descubierto una treintena de posibles mutaciones del gen NOD2/CARD15, hoy se sabe que sólo 3 de ellas se asocian a pacientes afectados por ECr (Duerr, 2003). Lakatos et al, 2006;Pena, 2006).…”