Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007570 (celiac disease)
 13,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. We previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II beta-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. We now report the isolation of this beta-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP beta chain. This celiac disease-associated HLA-DP beta-chain gene was flanked by HLA-DP alpha-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP alpha-chain genes of celiac disease patients also were studied by RFLP analysis; 84% of HLA-DR3, -DQw2 patients had a 16-kb Xba I fragment that was present in only 36% of HLA-DR3, -DQw2 controls. Moreover, 79% of these patients had both alpha- and beta-chain polymorphisms in contrast to 27% of controls. Thus, celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP alpha- and beta-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.
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PMID:An extended HLA-D region haplotype associated with celiac disease. 289 73

The genes of the human leukocyte antigen (HLA) region, the major histocompatibility complex (MHC) of humans, control a variety of functions involved in immune response and influence susceptibility to over 40 diseases. Theoretical studies in the development of models to determine the modes of inheritance of the HLA-associated diseases have led to a better understanding of the inheritance patterns in insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, hemochromatosis, celiac disease, and others. It is now clear that many of the HLA-associated diseases involve heterogeneity in their HLA components, as well as non-HLA genetic factors. This review is presented using HLA-associated diseases, and in particular IDDM, as the example of interest, but the observations and techniques presented have direct relevance to the study of all human diseases with a complex genetic component. Three methods for localizing disease-predisposing genes are presented: (1) association studies, including population, family, and relative predispositional effects, (2) affected sib pair and other affected-relative methods, and (3) lod score analysis. A variety of complementary methods for studying the mode(s) of inheritance of the alleles at the disease-predisposing locus and for identifying the alleles and amino acids directly involved in the disease process also are presented.
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PMID:HLA disease associations: models for the study of complex human genetic disorders. 759 90

Celiac disease is the classical food-sensitive enteropathy and is caused by an antigen-specific immunologic hypersensitivity response to gluten within the small intestinal mucosa. Antibody and T-cell hypersensitivity may play a role in vivo, but it is more likely that the primary problem is an inappropriate T-cell response to gluten. The deleterious effects of gluten in celiac patients can be completely explained by the immune-mediated alterations in upper small-intestinal mucosal shape; these alterations include the replacement of long villi and short crypts with short or absent villi and hyperplastic crypts. It is an extremely unusual disease in that it is highly linked to human leukocyte antigen (HLA)-DQ2, and CD4+ T-cell clones that recognize gluten in the context of DQ2 have been isolated from celiac mucosa lamina propria. HLA-DQ2 is commonly used in Whites, but the incidence of celiac disease varies greatly between different countries and with time, without any obvious explanation. Celiac disease is also unusual in that it has features of autoimmune disease. Patients with active disease have immunoglobulin (Ig)A antibodies in endomysium, an uncharacterized extracellular matrix protein, and the presence of these antibodies is very specific for this condition. However, because celiac disease is more common in IgA-deficient patients, the IgA antiendomysial antibodies are unlikely to be pathogenic.
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PMID:The immunologic basis for celiac disease and related disorders. 881 64

Celiac disease is a permanent intolerance to ingested gluten that results in immunologically mediated inflammatory damage to the small-intestinal mucosa. Celiac disease is associated with both human leukocyte antigen (HLA) and non-HLA genes and with other immune disorders, notably juvenile diabetes and thyroid disease. The classic sprue syndrome of steatorrhea and malnutrition coupled with multiple deficiency states may be less common than more subtle and often monosymptomatic presentations of the disease. Diverse problems such as dental anomalies, short stature, osteopenic bone disease, lactose intolerance, infertility, and nonspecific abdominal pain among many others may be the only manifestations of celiac disease. The rate at which celiac disease is diagnosed depends on the level of suspicion for the disease. Although diagnosis relies on intestinal biopsy findings, serologic tests are useful as screening tools and as an adjunct to diagnosis. The treatment of celiac disease is lifelong avoidance of dietary gluten. Gluten-free diets are now readily achievable with appropriate professional instruction and community support. Both benign and malignant complications of celiac disease occur but these can often be avoided by early diagnosis and compliance with a gluten-free diet.
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PMID:The widening spectrum of celiac disease. 1007 17

An 11-year-old girl presented with chronic urticaria (CU), antithyroid antibodies, and anemia. Celiac disease was diagnosed. The family history was positive for maternally derived CU and thyroid autoimmunity in three generations. Human leukocyte antigen typing disclosed human leukocyte antigen DQA1*0501 DQB1*0201 in both mother and child. CU was unresponsive to a gluten-free diet despite clinical and laboratory resolution of celiac disease in contrast to previous reports in adults. We believe that this is the first report of this association in a child, highlighting that CU may be a part of the spectrum of autoimmune phenomenon related to celiac disease.
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PMID:Celiac disease associated with familial chronic urticaria and thyroid autoimmunity in a child. 1042 42

With the aim to determine the frequency of human leukocyte antigen phenotypes of celiac disease in Turkey, thirty celiac patients fulfilling the European Society of Pediatric Gastroenterology and Nutrition criteria were included in the study. The mean age of the study population was 5.8 +/- 4.3 years and of the control subjects was 32.6 +/- 6.7 years. The human leukocyte antigens -A, -B, -DR and -DQ were studied serologically by micro lymphocytotoxic reaction. It was found that human leukocyte antigens A-25(10), -B8, -DR18(3) and -DQ2 were more significantly frequent in the celiac population than in the control group. Children with antigen -B8 showed a five times higher risk for celiac disease and those with antigen -DQ2 showed a nine times higher risk. It was determined that human leukocyte antigen -B4 had a protective role in celiac disease. The study suggests that the human leukocyte antigen -A25(10) is a phenotype particularly encountered in Turkish pediatric celiac patients.
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PMID:Human leukocyte antigens in Turkish pediatric celiac patients. 1077 Jun 56

Gliadin specific T cells in the small intestines of coeliac disease patients use the disease associated human leukocyte antigen-DQ2 molecules in their antigen recognition. In an exciting interplay with tissue transglutaminase, the immune system recognises modified gliadin peptides and mounts a phlogistic response. Moreover, the role for autoimmune phenomena and the mechanism of breaking of immunological tolerance remain elusive.
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PMID:Coeliac disease--all questions answered? 1199 Mar 98

The role of human leukocyte antigen (HLA) DQ2 heterodimer (DQA1*0501-DQB1*0201) in presenting gluten peptides to effector T cells in celiac disease (CD) has been well documented. Because HLA-DQ2 is carried on DR3 haplotypes due to linkage disequilibrium, such haplotypes are encountered more frequently in patients with autoimmune disease. This study analyzed 35 North Indian children below 15 years of age and diagnosed to have CD as per the ESPGAN criteria, which included histopathologic alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of antiendomysial antibodies. The HLA class I and class II alleles were determined by polymerase chain reaction-sequence-specific primers, sequence-specific oligonucleotide probe, and reverse line strip molecular techniques. A statistically significant positive association of the disease with HLA-DRB1*03 (94.2% versus 22.1% in controls, chi(2) = 73.4, p = 7.54E-11), and a negative association with DRB1*15 (chi(2) = 7.4, p = 6.5E-03) and DRB1*13 alleles was observed. The HLA-DQB1*0201 was observed in all the 35 patients (100%), whereas the DQ2 heterodimer alpha(0)beta(0) occurred in 97.1% of CD patients (31.4% in double dose, 65.7% in single dose) and revealed significant deviation from healthy controls (chi(2) = 102.08, p = 7.56E-11). Further analysis revealed involvement of multiple DR3+ve haplotypes with CD in Indians, of which A26-B8-DR3 was the most common DR3 haplotype among patients (34.28%, chi(2) = 40.57, p = 2.65E-10) followed by Ax-B21-DR3 (11.4%) (chi(2) = 13.8, p = 2E-04) and the classical Caucasian haplotype A1-B8-DR3 (5.7%). The former two haplotypes are characteristic of Asian Indians and are involved in the development of CD. We conclude that the high risk DR3 haplotypes that play a crucial role in the development of CD are unique in Asian Indians. Detailed analysis of these haplotypes in Indian patients with autoimmune diseases may help understand the influence of other intervening genes within the major histocompatibility complex.
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PMID:Pediatric celiac disease in India is associated with multiple DR3-DQ2 haplotypes. 1212 76

Distinctive arthritic patterns, some of which may parallel or even precede intestinal disease activity, are seen in inflammatory bowel disease. Some spondyloarthropathies are associated with transient ileocolic inflammation. Vasculitis frequently affects the gastrointestinal tract, predominantly manifesting with abdominal pain. In severe cases, intestinal ischemia and perforation may occur. Various arthritides are thought to be associated with other gastrointestinal diseases, such as celiac disease and hepatitis. The association between intestinal disease and arthritis is still being investigated. Interactions between the inflammatory intestinal cells and inflamed synovial cells have been demonstrated. Certain intestinal bacteria such as Klebsiella pneumoniae are suspected to play a role as triggers for the development of arthropathies. Genetic factors, especially human leukocyte antigen associations, are also being increasingly investigated for better characterization of the types of arthritis and possible prognostic implications. Various therapies, including nonsteroidal anti-inflammatory drugs, used to treat rheumatologic diseases have the potential to cause gastrointestinal complications.
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PMID:Gastrointestinal issues in children with rheumatologic disease. 1242 59

The chromosome region 2q33, which contains the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, has been reported in linkage and association with celiac disease (CD). In the present work we have tested the association between the polymorphism of the CTLA-4 exon 1 and susceptibility to CD in an Italian population, using case-control and family-based approaches. The +49 A/G dimorphism was analyzed in 86 patients, 144 ethnically matched controls, and 113 nuclear families by the polymerase chain reaction-restriction fragment length polymorphism method. A significantly higher frequency of the CTLA-4 +49A allele was observed in patients when compared with controls (p = 3 x 10(-2)). The segregation analysis in the 113 trios showed a preferential transmission of the A allele to the probands (chi(2)(TDT) = 4.85). When the patients were stratified according to the presence/absence of the high-risk human leukocyte antigen-DQ2 heterodimer, a significant difference was observed between the two groups, that is, the A allele was increased in the subjects without the DQ2 heterodimer (88.9% vs 73.5%, p = 8.3 x 10(-3)). The A allele was transmitted from heterozygous parents to eight of nine DQ2-dimer-negative patients. These data support CTLA-4 as a predisposing gene for CD in an Italian population with a prominent role in patients not carrying the high-risk human leukocyte antigen-DQ2 molecules.
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PMID:CTLA-4 +49 A/G dimorphism in Italian patients with celiac disease. 1255 33


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