Title: On the Genetics of Innate Immunity in Crohns Disease
Volume: 4
Issue: 7
Author(s): W. Klein, T. Griga, C. Folwaczny and J. T. Epplen
Affiliation:
Keywords:
crohn disease, innate immunity, genetic predisposition, association studies
Abstract: There is increasing evidence both from, animal models and clinical investigations that luminal bacteria play a pivotal role in the pathogenesis of Crohns disease (CD). In almost all murine models for spontaneous colitis, animals stay healthy as long as they are kept under germ free conditions. Antibacterial treatment reduces disease severity in some patients with CD. This aforementioned hypothesis is further supported by the identification of the first susceptibility gene for CD. Single nucleotide polymorphisms in the caspase recruitment domain 15 gene (CARD15, formerly known as NOD2) have been identified recently. The respective CARD15 alleles increase the risk of developing CD. The CARD15 protein is located in the cytoplasm of mononuclear cells where it is involved in the recognition of bacterial components leading to subsequent activation of nuclear factor kB. As rare alleles of the SNPs are not found in all patients with CD and as these alleles are found in healthy persons as well, variations in the CARD15 gene are neither necessary nor sufficient for the genetic predisposition to CD. Further genes are supposed to play a crucial role in the pathogenesis of CD. Disturbed activation of the innate immune system by bacterial antigens seems to be crucial in a subgroup of patients with CD. Genes involved in pathways of the innate immune system represent good candidate genes for the predisposition to CD. Abundant polymorphisms in these genes have been described. The putative role of these polymorphisms in the genetic predisposition to CD is revisited for this multifactorial model disease.
