HLA-DQ:Celiac disease vs inflammatory bowel disease

AIM To determine the genetic predisposition to celiacdisease(Ce D) in inflammatory bowel disease(IBD) patients by quantifying the frequency of Ce D-related human leucocyte antigen(HLA)(HLA-Ce D: HLA-DQ2 and-DQ8) in IBD patients globally, by type of IBD and gender, and by calculating the protective/risk contribution of these haplotypes in the development of the IBD disease.METHODS We conducted a prospective study with IBD patients from our Unit. Clinical information was gathered and blood was tested for HLA-CeD. The control group was made up of unrelated Valencian organ donors.RESULTS1034 subjects were analyzed: 457 IBD [207 ulcerative coliti(UC) and 250 Crohn's disease(CD)] patients and 577 healthy controls. 39% of the controls and 34% of the patients had HLA-Ce D(P = 0.0852). HLA-DQ2 was less frequent in UC patients(P = 0.0287), and HLA-DQ8 in CD(P = 0.0217). In women with UC, the frequency of DQ2.5 cis(DQB1*02:01-DQA1*05:01) was reduced ≥ 50% [P = 0.0344; preventive fraction(PF) = 13%]. PFs(7%-14%) were obtained with all HLACe D haplotypes. HLA DQB1*02:02-DQA1*02:01(HLADQ2.2) was more frequent in CD patients with respect to controls(P = 0.001) and UC patients(etiological fraction = 15%).CONCLUSION HLA-CeD is not more frequent in IBD patients, with an even lower frequency of HLA-DQ2 and-DQ8 in UC and CD respectively. HLA-DQ2.5 confers protection from the development of UC, especially in women, and HLADQ8 does so for the appearance of CD. HLA-DQ2.2 is present in 34% of the CD patients and may constitute a genetic risk factor for CD development.

Pathogenesis of Crohn's disease: Bug or no bug

The possibility of an infectious origin in inflammatory bowel disease(IBD)has been postulated since the first description of Crohn’s disease(CD).Many observations implicate bacteria as a trigger for the development of CD:lesions occur in regions with higher bacterial concentrations;aphthous ulcers occur in Peyer’s patches;inflammation resolves when the fecal stream is diverted and is reactivated following reinfusion ofbowel contents;severity of the disease is correlated with bacterial density in the mucosa;granulomas can contain bacteria;and susceptible mice raised in germfree conditions develop inflammation when bacteria are introduced in the 1990’s,several studies sought to establish a relationship with viral infections and the onset of IBD,finally concluding that no direct link had been demonstrated.In the past fifteen years,evidence relating IBD pathogenesis to Mycobacterium avium paratuberculosis,salmonella,campylobacter,etc.,has been found.The tendency now under discussion to regard microbiota as the primary catalyst has led to the latest studies on microbiota as pathogens,focusing on Escherichia coli,mainly in ileal CD.The present review discusses the literature available on these"bugs".