Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colonic epithelial cells (CEC) were isolated from actively inflamed mucosa of IBD patients and checked for HLA-DR, HLA-DP, and HLA-DQ. Half of the freshly isolated CEC from IBD tissue expressed DR, and one third were positive for DP and DQ. Normal human CEC were then cultured for 24 h and their expression of these markers in response to different types of in vitro stimulation was investigated. A significant increase in the expression of DR, DP and DQ was observed in response to the nonspecific mitogen phytohaemagglutinin (PHA), the lymphokine gamma-interferon (gamma-IFN) and the epidermal growth factor (EGF). The enhancement of DR expression was more marked than that of DP and DQ. The effect of gamma-IFN was more rapid and significantly more marked than that of either PHA and EGF for all three antigens. EGF appeared to be more potent than PHA in enhancing the expression of DP and DQ. The data from this study indicate that HLA-D region antigens can be induced on human CEC by different types of stimuli and provide further evidence that the expression of these markers in the colonic epithelium is a normal event the magnitude of which can increase under various circumstances. The data also suggest that the increased expression of HLA-D region antigens by IBD CEC occurs as a result of different mechanisms, and that this expression is an indicator of the active participation of the colonic epithelium to the mucosal inflammatory response.
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PMID:HLA-D region antigens on isolated human colonic epithelial cells: enhanced expression in inflammatory bowel disease and in vitro induction by different stimuli. 314 53

Prediction of type 1 diabetes mellitus (IDDM) and its identification in preclinical period is one of the central problems in modern medicine. They are based comprehensive genetic, immunologic and metabolic evaluations. We observed four hundred seven first-degree relatives of patients with IDDM (240 families in which one of the children or one of the parents had IDDM) have been included in the study. The study of HLA-DQA1, HLA-DQB1 polymorphic alleles and DRB1 genes and their combinations. The genetic study included searching HLA loci (HLA-DQA1, HLA-DQB1 polymorphic alleles and DRB1 genes) loci. To evaluate the genetic risk two approaches we used: first--carrying predisposing HLA-DQ alleles and DRB1-genes and it's combination (mainly associated in Russian population was DRB1*04-DQB1*0302, DRB1*04-DQA1*0301, DQA1*0301-DQB1*0302, DQA1*0301-DQB1*0302 and four susceptible alleles in A- and B- chains (Asp 57-, Arg 52+)) and second--IBD (identity by descent), in Russian population HLA-identical for 2 haplotypes sibs had risk of development of IDDM of 18%, for 1 haplotype--3%, for 0 haplotype-0.9%. The antibodies (ICA, IAA) prevalence rate has not depended on availability of predisposing HLA-DQ alleles and DRB1-genes and haploidentity of normal sibs and sibs with IDDM. However, GADA prevalence rate in groups having high predisposed alleles has been noticed as significantly higher (28.6%) comparing with 7.7% in groups that had no predisposing alleles (p < 0.05). The comparison of antibodies prevalence rate to sibs HLA-identity has shown the significant increase or GADA prevalence rate in group of siblings identical for one haplotype comparing with non-identical sibs (27.3% and 0% respectively, p < 0.001).
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PMID:[Genetic and immunologic aspects of type 1 diabetes mellitus]. 1263 78

Celiac disease (CD) is an intestinal disorder caused by an intolerance to gluten, proteins in wheat. CD is an HLA-associated disease: virtually all patients express HLA-DQ2 or HLA-DQ8. Recent work has shown that these disease-predisposing HLA-DQ molecules bind enzymatically modified gluten peptides and these HLA-DQ peptide complexes trigger inflammatory T-cell responses in the small intestine that lead to disease. In addition, gluten induces innate immune responses that contribute to the tissue damage that is characteristic for CD. Thus, CD patients are caught between a rock and a hard place: the disease is caused by a combination of adaptive and innate immune responses that both are triggered by gluten. These findings explain the disease-inducing properties of gluten and provide valuable clues for the development of alternative treatment modalities for patients. They also may be of relevance for our understanding of other multifactorial disorders including IBD and HLA-associated autoimmune diseases.
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PMID:Celiac disease: caught between a rock and a hard place. 1623 82

Patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D) carrying human leukocyte antigen (HLA)-DQ2/8 genotypes benefit from gluten withdrawal. Our objective was to compare gastrointestinal barrier function, mucosal inflammation, and transit in nonceliac IBS-D patients and assess association with HLA-DQ2/8 status. In 45 IBS-D patients who were naive to prior exclusion of dietary gluten, we measured small bowel (SB) and colonic mucosal permeability by cumulative urinary lactulose and mannitol excretion (0-2 h for SB and 8-24 h for colon), inflammation on duodenal and rectosigmoid mucosal biopsies (obtained in 28 of 45 patients), tight junction (TJ) protein mRNA and protein expression in SB and rectosigmoid mucosa, and gastrointestinal and colonic transit by validated scintigraphy. SB mucosal biopsies were stained with hematoxylin-eosin to assess villi and intraepithelial lymphocytes, and immunohistochemistry was used to assess CD3, CD8, tryptase, and zonula occludens 1 (ZO-1); colonic biopsy intraepithelial lymphocytes were quantitated. Associations of HLA-DQ were assessed using Wilcoxon's rank-sum test. Relative to healthy control data, we observed a significant increase in SB permeability (P < 0.001), a borderline increase in colonic permeability (P = 0.10), and a decrease in TJ mRNA expression in rectosigmoid mucosa in IBS-D. In HLA-DQ2/8-positive patients, ZO-1 protein expression in the rectosigmoid mucosa was reduced compared with that in HLA-DQ2/8-negative patients and colonic transit was slower than in HLA-DQ2/8-negative patients. No other associations with HLA genotype were identified. There is abnormal barrier function (increased SB permeability and reduced mRNA expression of TJ proteins) in IBS-D relative to health that may be, in part, related to immunogenotype, given reduced ZO-1 protein expression in rectosigmoid mucosa in HLA-DQ2/8-positive relative to HLA-DQ2/8-negative patients.
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PMID:Association of HLA-DQ gene with bowel transit, barrier function, and inflammation in irritable bowel syndrome with diarrhea. 2304 42