In 153 patients with IBD, 64 with Crohn's disease (CD), and 89 with ulcerative colitis (UC), as well as in 54 healthy controls (HC), the frequencies of four known di-allelic polymorphisms in the genes for TNF-alpha and lymphotoxin alpha (LTalpha) were investigated.
Further characterization of the precise mechanism of action of anti-TNF antibody therapy may further unravel the cause of immune dysregulation in Crohn's disease.
It was found that LP macrophages in Crohn's disease (CD) and ulcerative colitis (UC) display high levels of NF-kappa B DNA-binding activity accompanied by an increased production of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) alpha.
The tumor necrosis factor microsatellite haplotype a2blc2d4e1 has been found previously to be present in 24 percent of patients with Crohn's disease and only 5 percent of patients with ulcerative colitis.
TNF microsatellite markers and, for some families, additional HLA antigens were typed for 323 individuals from 49 Crohn's disease multiplex families to generate informative haplotypes.
Preliminary results have shown that antisense oligonucleotides (anti-ICAM), anti-cytokine antibodies (anti-TNF) or recombinant human cytokines (IL-10 or IL-11) are effective in some patients with Crohn's disease refractory to steroids.
Over the past 10 years these concepts have been used as the basis for successful anti-TNF therapy of autoimmune diseases like rheumatoid arthritis (RA) and Crohn's disease.
This study suggests that one of the genes responsible for UC may be the TNF gene, or an adjacent gene, and that TNFRSF1B gene polymorphisms contribute greatly to the increased onset risk of CD and to the disease behavior.
119 healthy, unrelated controls, 95 patients with Crohn's disease and 93 patients with ulcerative colitis were genotyped for the (G to A) -308 TNF-alpha promoter polymorphism on chromosome 6, the codon 497 EGFR polymorphism on chromosome 7 and the TaqI polymorphism of the VDR gene on chromosome 12.
The aim was to assess the value of C-reactive protein and TNF-alpha serum levels before treatment as well as the TNF -308 gene polymorphism in the prediction of response to infliximab treatment in Crohn disease.
T helper-type 1 (Th1) lymphocytes orchestrate much of the inflammation in Crohn's disease mainly via production of TNFalpha, which appears to play a pivotal role as a pro-inflammatory cytokine.
Further genetic associations of TNF(-857C) with IBD sub-phenotypes were seen for ulcerative colitis and for Crohn's disease, but only in patients not carrying common NOD2 mutations.
In a two-cohort study, a series of polymorphisms in the TNF, the TNF-R-I and in the TNF-R-II genes could be thoroughly excluded as pharmacogenetic markers for a treatment response to infliximab and as etiologic factors for Crohn's disease, respectively.
This study suggests that one of the genes responsible for UC may be the TNF gene, or an adjacent gene, and that TNFRSF1B gene polymorphisms contribute greatly to the increased onset risk of CD and to the disease behavior.
The aim of the study was to determine the prevalence of the tumor necrosis factor alpha (TNF-alpha) promoter polymorphisms at positions -238 and -308, and to measure the serum CRP levels in CD and UC patients and in a healthy population.