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Review
. 2005 Jan;54(1):162-7.
doi: 10.1136/gut.2003.035600.

Genotypes and phenotypes in Crohn's disease: do they help in clinical management?

C Gasche  1 , P Grundtner
Affiliations
Review

Genotypes and phenotypes in Crohn's disease: do they help in clinical management?

C Gasche et al. Gut. 2005 Jan.

Erratum in

  • Gut. 2005 Mar;54(3):442
No abstract available

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Figures

Figure 1
Figure 1
Caspase activation and recruitment domain 15 (CARD15) is mainly expressed in the granulocyte-macrophage lineage (including dendritic cells) and also in Paneth cells of the intestinal tract. CARD15 is activated by binding of naturally occurring muropeptides, enzymatic degradation products of peptidoglycans (PGNs) derived from bacterial cells walls. Their presence triggers CARD15 oligomerisation (as indicated by three overlapping CARD15 molecules) and recruitment of RIP-like interacting CLARP kinase (RICK) via CARD-CARD interaction. RICK then activates the nuclear factor κB inhibitor (IκB) kinase complex (IKK) via phosphorylation of IKKγ. The ΙΚΚ complex next phosphorylates IκB resulting in nuclear factor κB (NFκB) translocation to the nucleus and transcriptional activation of NFκB responsive genes such as proinflammatory cytokines or defensins.
Figure 2
Figure 2
Three caspase activation and recruitment domain 15 (CARD15) variants (R702W, G908R, and L1007fs) within the leucine rich repeat (LRR) were initially described to genetically predispose to the development of Crohn’s disease. These variants are disease specific because they do not confer risk to other chronic inflammatory or autoimmune diseases. In the intestinal tract, CARD15 is primarily expressed in Paneth cells, which are critical in enteric antibacterial defence. In CARD15 mutant individuals, nuclear factor κB (NFκB) activation is reduced and thus the necessary antibacterial response, such as expression of defensins, does not occur. Chronic NFκB activation through alternative pathways is regarded as secondary to the lack of an appropriate antibacterial response. Paneth cells are most numerous in the terminal ileum and seem to be of local importance. A CARD15 deficit in Paneth cells, as present in homozygous or compound heterozygous mutants, is phenotypically related to Crohn’s ileitis. NBD, nucleotide binding domain.
See this image and copyright information in PMC

References

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