Kiolm, I believe the reason is that both celiac disease and IBD people have leaky guts. Because we have a leaky gut, the immune system recognizes the gluten protein, goes crazy and attacks the colon. Gluten is also inflammatory.
Antibody response to dietary and autoantigens in G alpha i2-deficient mice.
Uhlig HH, Hultgren Hörnquist E, Ohman Bache L, Rudolph U, Birnbaumer L, Mothes T.
Department of Paediatrics, University of Leipzig, Germany.
Abstract
BACKGROUND: Mice with a targeted mutation in the G protein subunit G alpha i2 gene develop a colonic mucosal inflammation, with a highly activated B-cell response. We wanted to investigate whether this increased B-cell activity was directed against dietary antigens and/or various self tissues.
METHODS: The level of antibodies specific for dietary (gliadin, soya and fish meal) antigens was measured by ELISA. Reactivity against self antigens was measured by immunohistochemistry on cryo-sectioned mouse and rat tissue. Sera and intestinal lavages were analysed from G alpha i2-/- mice before and after development of colitis and in age-matched wild type litter mates.
RESULTS: Titres of antibodies against dietary antigens were significantly enhanced both in serum and in large intestinal lavages from G alpha i2-/- mice with ongoing colitis but not prior to disease, as compared to wild type mice. The autoreactivity to self tissues was significantly increased in G alpha i2-/- mice both before and after development of colitis as compared to litter mate control animals. Self tissue reactivity was directed not only against epithelial cells of the colon, small intestine and gastric glands, but also against smooth muscle cells, hepatocytes, bile duct cells, renal tubule and collecting tubule cells of the kidney. In analogy to human ulcerative colitis, autoantibodies against epithelial cells, bile duct epithelium and neutrophil granulocytes were found.
CONCLUSIONS: Earlier increase in levels of autoantibodies (before onset of colitis) than of food antibodies (after onset of colitis) suggests the latter response to be a secondary phenomenon to e.g. a destroyed barrier function.
another one:
Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitis.
Wapenaar MC, Monsuur AJ, van Bodegraven AA, Weersma RK, Bevova MR, Linskens RK, Howdle P, Holmes G, Mulder CJ, Dijkstra G, van Heel DA, Wijmenga C.
Genetics Department, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
[email protected]Comment in:
* Gut. 2008 Apr;57(4):438-40.
* Gastroenterology. 2008 Dec;135(6):2145-7; discussion 2147.
Abstract
BACKGROUND: Coeliac disease (gluten-sensitive enteropathy; GSE) and inflammatory bowel disease (IBD) are common gastrointestinal disorders. Both display enhanced intestinal permeability, initiated by gluten exposure (GSE) or bacterial interactions (IBD). Previous studies showed the association of both diseases with variants in MYO9B, presumably involved in epithelial permeability.
AIM: It was hypothesised that genetic variants in tight junction genes might affect epithelial barrier function, thus contributing to a shared pathogenesis of GSE and IBD.
METHODS: This hypothesis was tested with a comprehensive genetic association analysis of 41 genes from the tight junction pathway, represented by 197 tag single nucleotide polymorphism (SNP) markers.
RESULTS: Two genes, PARD3 (two SNPs) and MAGI2 (two SNPs), showed weak association with GSE in a Dutch cohort. Replication in a British GSE cohort yielded significance for one SNP in PARD3 and suggestive associations for two additional SNPs, one each in PARD3 and MAGI2. Joint analysis of the British and Dutch data further substantiated the association for both PARD3 (rs10763976, p = 6.4 x 10(-5); OR 1.23, 95% CI 1.11 to 1.37) and MAGI2 (rs6962966, p = 7.6 x 10(-4); OR 1.19, 95% CI 1.08 to 1.32). Association was also observed in Dutch ulcerative colitis patients with MAGI2 (rs6962966, p = 0.0036; OR 1.26, 95% CI 1.08 to 1.47), and suggestive association with PARD3 (rs4379776, p = 0.068).
CONCLUSIONS: These results suggest that coeliac disease and ulcerative colitis may share a common aetiology through tight junction-mediated barrier defects, although the observations need further replication.
and
Increased epithelial gaps in the small intestines of patients with inflammatory bowel disease: density matters.
Liu JJ, Wong K, Thiesen AL, Mah SJ, Dieleman LA, Claggett B, Saltzman JR, Fedorak RN.
Department of Medicine, Division of Gastroenterology (J.J.L., K.W., S.J.M., L.A.D., R.N.F.), Department of Laboratory Medicine and Pathology (A.L.T.), University of Alberta, Edmonton, Alberta, Canada; Department of Biostatistics (B.C.), Harvard School of Public Health, Gastroenterology Division (J.R.S.), Brigham and Women's Hospital, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Epithelial gaps created by shedding of epithelial cells in the small intestine can be visualized by using confocal laser endomicroscopy (CLE). The density of epithelial gaps in the small bowels of patients with inflammatory bowel disease (IBD) and controls without IBD is unknown.
OBJECTIVE: To determine whether the epithelial gap density in patients with IBD is different from that in controls.
DESIGN: Prospective, controlled, cohort study.
SETTING: A tertiary-care referral center.
PATIENTS: This study involved patients with IBD and control patients without IBD undergoing colonoscopy.
INTERVENTION: Probe-based CLE (pCLE) was used to image the terminal ileum.
MAIN OUTCOME MEASUREMENTS: The primary outcome of the study was gap density, defined as the total number of gaps per 1000 cells counted in adequately imaged villi by using pCLE. The pCLE images were blindly reviewed, and the number of epithelial gaps and cells were manually counted. The secondary outcomes were correlation of gap density with disease activity,
location, and severity of clinical disease.
RESULTS: There were 30 controls and 28 patients with IBD. Of the patients with IBD, 16 had Crohn's disease, and 12 had ulcerative colitis. The median epithelial gap densities for controls and patients with IBD were 18 and 61 gaps/1000 cells, respectively (P < .001). Gap density did not correlate with disease activity. Patients with ulcerative pan-colitis tended toward gap densities lower than those of patients with limited colitis (32 versus 97 gaps/1000 cells, P = .06). Patients with IBD with severe clinical disease also had lower median gap densities (37 vs 90 gaps/1000 cells, P = .04).
LIMITATIONS: A single-center study.
CONCLUSION: The epithelial gap density was significantly increased in patients with IBD compared with controls. (Clinical trial registration number: NCT00988273.).