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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous work on the inheritance of disease has often used certain measures of HLA haplotype concordance (such as the number of haplotypes "identical by descent," IBD) among affected siblings from each of a number of sibships, each of which contains at least two affected siblings. Here we introduce a new measure of HLA haplotype discordance between the affected and unaffected siblings of each sibship (provided there is at least one of each). We show how the measure can be used to give a simple test for inheritance, which we exemplify with data.
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PMID:HLA haplotype discordance. 323 57

The colonic epithelial expression of HLA-DR molecules and of other markers of cell membrane perturbation was investigated by immunofluorescence in biopsy specimens from patients with ulcerative colitis and Crohn's disease. It was found that in virtually all specimens from either groups showing active inflammation there was a diffuse epithelial expression of HLA-DR molecules. There was no relation between the grading of active inflammation and the epithelial expression of HLA-DR antigens. The epithelium of virtually all specimens from the macro and microscopically uninvolved areas of patients with active colitis and from patients with histologically quiescent colitis showed no detectable expression of HLA-DR molecules. The counts of isolated lamina propria lymphocytes expressing the transferrin receptor and the interleukin 2 receptor were higher in specimens with HLA-DR+ epithelium than in those with a HLA-DR- epithelium. Twenty-nine of the 35 (83%) HLA-DR positive specimens proved to express the 4F2 antigen on their epithelium and 19 (54%) were positive for the transferrin receptor. All sections positive for either the 4F2 antigen or the transferrin receptor were also HLA-DR positive while all HLA-DR negative sections were also negative for either of the two other markers. Data in this study suggest that in active IBD the epithelial participation in active inflammation is associated with a sequence of cell membrane rearrangements, and that the expression of HLA-DR molecules is a part of this sequence.
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PMID:HLA-DR antigens on colonic epithelial cells in inflammatory bowel disease: I. Relation to the state of activation of lamina propria lymphocytes and to the epithelial expression of other surface markers. 330 19

An adaptation of the sib pair method is given for testing the independence of transmission of Gm and the disease, using variable X (which gives information on the phenotypic identity of a sib pair for Gm). Then the joint distribution of IBD for HLA and X for Gm among affected sib pairs was derived under different two-locus models (multiplicative and other) in which one locus is strictly linked to HLA and the other to Gm. We also propose a test for a joint effect of HLA and Gm and whether this effect is multiplicative or not.
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PMID:Two-disease locus model: sib pair method using information on both HLA and Gm. 378 Dec 39

It has been shown that genetic factors within the HLA region are involved in the etiology of several diseases. For some of these, the existence of another genetic factor has been suggested, although not proven. A possible way to give evidence for another locus (G) is to show that the disease and an unlinked HLA-marker locus (M) do not segregate independently. The usual lod-score method, which assumes monogenic inheritance, is inappropriate for this test. We propose a correction of this method for performing a linkage analysis between the G and M loci, taking into account the role of HLA. A very simple way of using the HLA information is by modifying, for each individual of a pedigree, the penetrance values at the G locus according to the number of HLA haplotypes shared with the index case. These penetrance values are inferred from the observed IBD (identity-by-descent) distribution of HLA haplotypes in a sample of affected sib-pairs. The advantage of using this empirical distribution is that it is not based on any assumptions concerning the mode of inheritance at the HLA-linked locus. This correction method was established using a two-locus model with restrictive assumptions. Its value is discussed for various sets of parameters in more general and realistic two-locus models using simulations.
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PMID:HLA-associated diseases: a new method for performing linkage analysis with other markers than HLA. 659 41

In present study, the subsets of activated (HLA-DR+) lamina propria T cells were evaluated in ulcerative colitis (UC) mucosa using three-color flow cytometry. Activated suppressor-inducer T cells (T(si)), helper T cells (Th) and cytotoxic T cells (Tc) were increased in affected mucosa of UC patients not given steroid hormones (SH) compared with in the normal control mucosa. It was supposed that the increase of activated T(si) was the secondary change of inflammation, because this change was demonstrated in non-IBD colitis too. However, the increase of activated Th and Tc might indicate the immunological abnormalities related to the pathogenesis of UC, because these changes were demonstrated only in UC, not in non-IBD colitis. On the other hand, no increase of these activated T cells were demonstrated in affected mucosa of UC patients given SH, perhaps reflecting the immuno-suppressive effect of SH.
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PMID:[Evaluation of activated T cells among isolated colonic mucosal lymphocytes in ulcerative colitis--using three color flow cytometry]. 834 70

The complex genetics of IBD is characterized by more than one susceptibility locus, genetic heterogeneity, incomplete penetrance, and probable gene-gene and gene-environment interactions. Functional candidate gene association studies during the past few decades have revealed only modest associations between IBD and genetic variants in the HLA genes and a limited number of other genes that are involved in immune regulation and the inflammatory response. Important advances in IBD genetics research have come about from systematic genome searches for IBD loci. The identification of Crohn's disease-associated NOD2 genetic variants that appear to alter the innate immune response to bacteria is a seminal finding that perhaps is the greatest advance toward understanding the pathogenesis of IBD in decades. The future discovery of other IBD genetic risk factors, facilitated by the completion of the human genome sequencing and annotation, may allow the development of better therapies, possibly including preventive therapies, for patients with Crohn's disease and ulcerative colitis.
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PMID:The genetics of inflammatory bowel disease. 1212 44

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

Genetic factors, among which the HLA class II coding genes, are implicated in IBD pathogenesis. When considering the ethnic heterogeneity of the studied population and the IBD clinical heterogeneity, UC appears more dependent to HLA genes than CD. UC and HLA genes: HLA DR 4 gene would protect from UC. HLA DR2 gene, particularly the DRB 1 * 1502 allele, is predisposing for more severe forms necessitating a corticotherapy, while DRB 1 * 0301 allele is associated with less needs for surgery. CD and HLA genes: HLA DR 7 gene and the DRB 3 * 0301 allele predispose to CD, while HLA DR 2 and DR 3 genes may be protective factors. Thus, for MC patient, the DRB 1 * 0301/DQB*0201 haplotype might be associated with less occurrence of fistulas or severe forms requiring immunosuppressive therapy.
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PMID:[The role of major histocompatibility complex genes in the pathogenesis of chronic inflammatory bowel diseases]. 1293 47

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

Partial or total CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain are among the autosomally inherited SCID presenting with T-B+NK+ phenotype with lymphopenia. The clinical findings are generally severe in all except for CD3 gamma deficiency. Here we present a 10-month-old CD3 gamma deficient boy with IBD. The patient had suffered from intractable diarrhea, recurrent pulmonary infections and oral moniliasis since two months of age. Following the first allogeneic HSCT from his HLA-identical (6/6) sister after a reduced intensity regimen, a second transplantation was performed five months later. On day +19 after second transplantation, the CD3 TCR alpha/beta chain expression increased to 66% with development of full donor chimerism (98.6%). A significant improvement in diarrhea, perianal lesions, and rectal fistula was observed suggesting an improvement in inflammatory bowel disease. The patient died at home on day +50 with a sudden respiratory failure secondary to an undetermined infection. The case was interesting being the first reported case with SCID and inflammatory bowel disease who responded very well to HSCT by full recovery of intractable diarrhea, failure to thrive, laboratory findings, and improvement of fistula formation.
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PMID:Hematopoietic stem cell transplantation in a CD3 gamma-deficient infant with inflammatory bowel disease. 1848 19


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