This spotlight article summarises the common gastrointestinal ( GI ) immune-mediated diseases , their clinical presentations , disease course , and their incidence and prevalence for easy reference
Silvio Danese MD PhD IRCCS Ospedale San Raffaele ; University Vita-Salute San Raffaele Milan , Italy
Three of the most common gastrointestinal autoimmune / immune-mediated diseases are inflammatory bowel disease ( IBD ), which includes Crohn ’ s disease ( CD ), ulcerative colitis ( UC ), and coeliac disease . Although their clinical presentations have been known for some time , the underlying causes are not fully understood . At present , these conditions are treatable but not curable . In recent years , a greater understanding of some of their associated molecular biology has begun to suggest possible causative mechanisms . Understanding these mechanisms could help to point the way for future treatments .
Autoimmune diseases arise when self-antigen tolerance fails and the immune system turns its antimicrobial defences upon healthy tissues . 1 , 2 The result is tissue injury , inflammation and organ or system malfunction . In coeliac disease and IBD , the main organ in question is the gut – predominantly the small and large bowel .
Gastrointestinal autoimmune diseases result from an interplay between certain factors , including environmental factors , a genetic predisposition , and the gut microbiome . Disruptions of the integrity of the gut barrier (‘ leaky gut ’) and antimicrobial peptide secretion are also believed to be involved . 3 , 4 Furthermore , abnormal interactions between the microbiome and the immune system in genetically susceptible individuals may also contribute to the development of these diseases .
IBD Incidence and prevalence IBD is estimated to affect some 4.2 million people globally . 1 Europe , North America and Oceania have the highest incidence rates , but incidence in Eastern Europe , Asia and South America is on the rise . 5 Rates vary considerably and North – South and East – West gradients have been described in Europe , with higher rates in the North and West and lower rates in the South and East . The prevalence of CD and UC in Europe range from 1.5 to 213 cases per 100,000 and from 2.4 to 294 cases per 100,000 , respectively . 5
Caucasians are most prone to IBD . Both CD and UC are polygenic , but CD is more likely to be associated with family history than UC . Peak incidences of UC and CD are in the second to fourth decade of age . 1
Genetic susceptibility First-degree relatives are five times more likely to develop IBD than those without IBD . 1 There is a possibility that some genes
20 | hospitalpharmacyeurope . com are shared by both CD and UC as the conditions can occur within the same family . 1 A total of 163 IBD-associated gene loci have been identified , of which 110 are associated with both diseases , 30 with CD , and 23 with UC . 1
Genetic analyses have identified two autophagy-related genes in IBD : ATG16L1 and IRGM . Autophagy plays an important role in intracellular homeostasis , degrading cytosolic contents and organelles , resisting infection , and eliminating microorganisms inside the cell . 1
Intestinal microbial flora In contrast to healthy control individuals , IBD patients are reported to have unstable gut microbiota ; specifically , a reduction in the diversity of species , which is considered one of the triggers for IBD . 1 In addition , there is evidence to support an underlying role of gut dysbiosis in IBD . 3
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