Crohn’s

Crohn’s is one of two major forms of Inflammatory Bowel Disease, the other being Ulcerative Colitis. Crohn’s differs from ulcerative colitis in that Crohn’s can affect any part of the gastrointestinal tract from the mouth to the anus, whereas ulcerative colitis mainly affects the large intestine. Crohn’s disease is characterised by abdominal pain, diarrhoea, which may be bloody, vomiting and weight loss. Crohn’s is often associated with complications outside of the gastrointestinal tract such as skin rash, arthritis, Uveitis, tiredness and lack of concentration. Onset of Crohn’s during childhood can have a significant effect on development.

The specific cause of Crohn’s is unknown but epidemiological studies do suggest a dysregulation of the immune response against the gut flora in a genetically susceptible individual, perhaps as a result of infection of the gut with an atypical microbe. Other environmental factors do perhaps play a part with some studies showing that smoking and appendectomy may act as triggers.

The most consistently replicated association of Crohn’s disease is with the HLA class II allele HLA-DRB1*07. The association is specifically in patients with ileal involvement. HLA-DRB1*01:03 has also been shown more recently to be associated with Crohn’s. As with ulcerative colitis, HLA-DRB1*01:03 may be associated with more severe disease, as defined by patients who require colectomy. HLA-DRB1*15:01 appears to confer protection against Crohn’s.

The advent of genome wide association studies have identified a large number of potential candidate genes which are being studied for association with Crohn’s. Of particular interest are the innate pattern recognition receptors ‘Nucleotide-binding Oligomerisation Domain containing 2’ / ‘Caspase Recuitment Domain family, member 15’ (NOD2/CARD15). NOD2/CARD15 is a member of the family of pattern recognition receptors that recognise microbial components. NOD2/CARD15 expression is high in the intestinal crypts.

The association between HLA and Crohn’s is of low specificity and sensitivity, limiting the value of genetic testing for diagnostic purposes. In addition, as Crohn’s shares some HLA gene susceptibility with ulcerative colitis, e.g. HLA-DRB1*01:03, it is not possible to use HLA typing to distinguish Crohn’s from ulcerative colitis. Knowledge of the HLA type of an already diagnosed Crohn’s patient may be of value in helping to predict disease course and may indicate treatment options. This may for example include the use of infliximab as an anti-TNF agent for certain stages of Crohn’s disease.


Do you or someone you know suffer from Crohn’s or are you a researcher working in this area? Please join the conversation. Leave a comment. Thanks.

 


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