XIAP variants in male Crohn’s disease Zeissig et al, Gut, Jan 2015
Immune function defects have been described in patients with IBD and may contribute to the development of intestinal inflammation. Several genes regulating the immune system have been implicated, but the clinical presentation across patients is often determined by the architecture of the individual’s own mutation profile. In some individuals monogenic diseases (diseases with single gene defects) can present solely with IBD-like symptoms with intestinal inflammation and often refractory to conventional therapy. However, due to lack of routine genetic tests in the current clinical diagnostics, the underlying genetic defect remains unidentified and patients are treated based on generic treatment guidelines.
In this paper, the authors observed mutations in the ‘XIAP’ gene in approximately 4% of their male patients with Crohn’s disease. The cohort consisted of 275 paediatric IBD including 91 males with CD. While mutations in this gene are known to be associated with a distinct medical condition presenting with immune deficiency called X-linked lympho-proliferative disease type 2 (XLP2), a subset of CD patients described here showed intestinal inflammation in the absence of XLP2. This supports the concept that specific immune defects can masquerade as IBD and therefore may not respond to routine treatment used in IBD. In the future, it may be possible to group patients based on their gene profile and offer an individualised treatment plan for better clinical outcomes.