Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA-DR, DQ, and DP restriction fragment genotyping was undertaken in 23 dermatitis herpetiformis patients and 53 healthy control subjects. HLA-DQw2 was present in 100% of patients with dermatitis herpetiformis (23 of 23) versus 40% of control subjects (21 of 53). Significant secondary associations occurred with HLA-DR3 (91% of patients versus 28% of control subjects) and DPw1 (39% of patients versus 11% of control subjects). Dermatitis herpetiformis and coeliac disease thus share an identical HLA class II association. It is likely that HLA class II genes directly influence the immune responses leading to mucosal damage in both diseases. The strongest candidate for disease susceptibility to dermatitis herpetiformis is DQw2. The HLA molecule most likely to be involved in coeliac disease is a specific DQ alpha/DQ beta heterodimer, encoded in cis arrangement in DR3 haplotypes or in trans arrangement in a DR5, 7 genotype. Our data on dermatitis herpetiformis patients fits this model perfectly. All these patients are capable of expressing this molecule, which may be responsible for the gluten sensitive enteropathy seen in a subgroup of patients with dermatitis herpetiformis and coeliac disease.
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PMID:HLA association with dermatitis herpetiformis is accounted for by a cis or transassociated DQ heterodimer. 167 26

Dermatitis herpetiformis (DH) is a pruritic, papulovesicular skin disease characterized in part by the presence of granular deposits of IgA at the dermal-epidermal junction, an associated gluten sensitive enteropathy (GSE), and a strong association with specific human histocompatibility leukocyte antigens (HLA). Initial investigations revealed that 60% to 70% of patients with DH expressed the HLA antigen B8 (normal subjects = 21%). Further investigation of the HLA associations seen in patients with DH has revealed an even higher frequency of the HLA class II antigens HLA-DR3 (DH = 95%; normal = 23%), HLA-DQw2 (DH = 100%; normal = 40%), and HLA-DPw1 (DH = 42%; normal = 11%). Analysis of the genetic linkage of HLA antigens has revealed that the strongest HLA association in patients with DH is with the HLA class II antigens DR3 and DQw2. This article will discuss current studies regarding the role of HLA associations and DH and the role this strong HLA association may play in the pathophysiology of DH.
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PMID:Immunogenetics of dermatitis herpetiformis. 193 73

Dermatitis herpetiformis is a rare blistering skin disease characterized in part by granular IgA deposits at the dermoepidermal junction, an associated gluten-sensitive enteropathy, and a strong association with the human histocompatibility leukocyte antigen (HLA)-A1 (74% of patients with dermatitis herpetiformis), -B8 (88%), -DR3 (95%), and -DQw2 (100%). Dermatitis herpetiformis is rarely seen in American blacks and some investigators have postulated that this finding may be due to the decreased frequency of HLA-A1 and -B8 in American blacks compared with Caucasians (American blacks: HLA-A1 = 15.3%, HLA-B8 = 10.7%; Caucasian: HLA-A1 = 26.4%, HLA-B8 = 18.3%). This report describes two American blacks with dermatitis herpetiformis and reports the results of HLA typing of these subjects for HLA-A, -B, -C, -DR, and -DQ antigens. HLA typing revealed that neither patient expressed HLA-A1 or -B8; however, both patients did express the class II antigens most frequently seen in dermatitis herpetiformis, HLA-DR3 and -DQw2. Comparison of HLA class II antigen frequency in normal American blacks and Caucasians reveals a similar frequency of HLA-DR3 and -DQw2 (American blacks: HLA-DR3 = 27.6%, HLA-DQw2 = 40.9%; Caucasian: HLA-DR3 = 22.6%, HLA-DQw2 = 32.9%). These data confirm the importance of the HLA class II region in the pathogenesis of dermatitis herpetiformis. In addition, these data suggest that the rare occurrence of dermatitis herpetiformis in American blacks is not due to the decreased frequency of the HLA class I antigens -A1 and/or -B8 but rather is related to differences in the HLA class II region not detected by routine HLA typing.
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PMID:Dermatitis herpetiformis in two American blacks: HLA type and clinical characteristics. 231 29

CD is a gluten-sensitive enteropathy, strongly associated with expression of the DQA1*0501, DQB1*0201 genotype. CD patients have an increased risk of malignancy, particularly EATCL. However, it is controversial as to whether adults with EATCL represent a subgroup of patients with CD or should be regarded as a distinct entity. To investigate the genetic relationship between CD and EATCL, HLA class II DRB1, DQA1, and DQB1 typing of peripheral blood, frozen or paraffin-embedded biopsy tissue obtained from Caucasian patients with CD (n = 91) or EATCL (n = 47) was performed by PCR-SSOP typing. Genotype frequencies were compared with those observed in 151 unrelated control individuals. A total of 83 (91%) of 91 CD patients were of DQA1*0501, DQB1*0201 genotype (pc < 10(-6), RR = 522.2), compared with 40 (93%) of 43 EATCL patients (pc < 10(-6), RR = 44.2) with amplifiable DNA versus 35 (23%) of 151 controls. DRB1*03 frequencies were also elevated in both patient groups (79 of 91 in CD [87%; pc < 10(-6), RR = 24.5] and 38 of 40 in EATCL [95%; pc < 10(-6), RR = 70.7]) compared with controls (32 of 151, 21%). These results confirm previous studies of HLA associations in CD and also suggest that EATCL arises in individuals with the DQA1*0501, DQB1*0201 CD-predisposing genotype. However, the frequency of DRB1*03,04 heterozygotes was significantly increased in the EATCL group (16 of 40, 40%) compared with both control individuals (3 of 151, 2%; pc < 10(-6), RR = 32.9) and uncomplicated CD patients (6 of 91, 7%; pc = 0.04, RR = 9.4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA-DRB, -DQA, and -DQB polymorphism in celiac disease and enteropathy-associated T-cell lymphoma. Common features and additional risk factors for malignancy. 755 26

Classical dermatitis herpetiformis (DH) is associated with similar HLA class I, II and III polymorphisms to coeliac disease (CD). The two diseases share distinctive pathological changes to the small intestinal mucosa which reverse on withdrawal of dietary gluten. In order to determine the locus primarily associated with DH, and to examine whether there is a common genetic link predisposing to the enteropathy seen in both DH and coeliac disease, HLA-DR, DQ and DP subregion associations were investigated by HLA genotyping in 23 DH patients and 64 healthy controls. We also studied polymorphisms of the TAP2 locus, which is located between the DP and DQ subregions. Genotyping was carried out by PCR of genomic DNA with allelic assignment by sequence-specific oligonucleotide (SSO) hybridization or amplification refractory mutation system (ARMS). The strongest associations in the patient group were with HLA DRB1*0301 (91% vs 22% of controls), HLA DQB1*02 (100% vs 32% of controls) and DPB1*0101 (39% and 14%). These associations are similar to those described for CD. 100% of DH patients were positive for the DQA1*0501/DQB1*02 dimer in cis or trans and, by analogy with CD, this is probably responsible for presenting gliadin peptide implicated in the disease process. Homozygosity for DQ2 was significantly increased in the CD patient group compared to the DH patient group (65% versus 39%), and so differences in dosage of HLA class II genotypes between DH and CD may be responsible for the milder gastrointestinal symptoms characteristic of DH.
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PMID:HLA class II region genes and susceptibility to dermatitis herpetiformis: DPB1 and TAP2 associations are secondary to those of the DQ subregion. 885 85

Celiac disease is a common HLA-DQ2-associated enteropathy caused by an abnormal T-cell-mediated immune response to ingested wheat gliadin proteins. We have previously isolated in situ activated mucosal T cells from celiac disease patients and demonstrated that these T cells were gliadin specific and predominantly DQ2 restricted. In contrast to this, gliadin-specific T cells isolated from peripheral blood display a variable HLA restriction pattern, thereby indicating that the skewed DQ restriction of T cells resident in the celiac lesions could be dictated by a preference for DQ-mediated antigen presentation in the mucosa of CD patients. To address this, we analyzed the HLA restriction of T cells recognizing astrovirus, a common gastroentetitis virus, isolated from intestinal mucosa of six celiac disease patients. As an internal control, gliadin-specific T cells were isolated and analyzed in parallel. The gliadin-specific mucosal T cells were marked in their DQ2 restriction, whereas the parallel astrovirus-specific T cells were predominantly restricted by DR molecules. Our data indicate that the repertoire of T cells present in celiac lesions is determined by the priming antigen(s) and not by a skewing in the expression of functional HLA class II isotypes in the disease affected small intestinal mucosa.
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PMID:HLA restriction patterns of gliadin- and astrovirus-specific CD4+ T cells isolated in parallel from the small intestine of celiac disease patients. 986 29

Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous atrophy and crypt cell hyperplasia. It has a very strong HLA class II association to the DQ locus. The nature of the involvement of the DQ locus in the susceptibility to CD has been examined by tissue culture experiments, association and peptide binding studies. We examined the role of the DQ molecules in the pathogenesis from the perspective of a genetic family study. Using flanking microsatellite markers to the class II region of the MHC to establish the parental origin of the susceptibility DQ alleles, we have evidence suggesting that the HLA association is probably due to the necessity to have these DQ alleles in order to express CD and there is no support for the presence of a rare mutation within the DQ alleles nor any rare HLA-linked gene nearby in linkage disequilibrium with the DQ locus. This approach is applicable to other diseases demonstrating strong association with common alleles, and can be used to predict whether screening the region for rare mutations is likely to be worthwhile.
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PMID:Common HLA alleles, rather than rare mutants, confer susceptibility to coeliac disease. 1073 34

Celiac disease is an auto-immune enteropathy involving genetic factors. It is associated in almost all the patients, to specific susceptibility alleles encoding histocompatibility antigens (HLA for human leucocyte antigen), specifically certain variants of the HLA-DQ2, and the HLA-DQ8 HLA class II molecules. Its estimated prevalence is 1% in the european and north-american populations. However, although these alleles represent the main genetic factor for this disease, they do not explain it on their own, as they are expressed by up to 30% of the population. Recent immunological advances allowed identifying the immunodominant epitopes of gluten, to establish the role of tissue transglutaminase in the disease and to define at the atomic level the presentation of these antigens by the HLA-DQ molecule. It is noteworthy that the HLA susceptibility alleles only account for 40% of the whole genetic risk, and the challenge is now to explain the remaining 60%. Genome-wide association studies using the DNA arrays technology to screen single nucleotide polymorphisms to pinpoint candidate regions and genes, have started to provide answers, but contradictory results sometimes still persist. Most of the genes emerging as statistically significantly associated with celiac disease are involved in the immune response, and suggest that the situation is complex.
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PMID:[Immunogenetics of celiac disease]. 2161 7

Celiac disease is a complex chronic intestinal disorder driven by an immune response against the gliadin fraction of gluten: many factors are involved in the pathogenesis of the disease, and among these Interleukin-10 could play an important role. In the present study, the -1082A>G, -819T>C and -592A>C IL10 functional polymorphisms were analyzed in 565 celiac patients and 576 healthy controls from north-eastern Italy, stratified for HLA class II celiac disease risk haplotypes. No significant differences were observed for the three IL10 polymorphisms distribution between celiac patients and controls with the exception of a slightly increased risk for the -1082A allele in HLA-DQ8 male individuals. Although our findings suggest that the IL10 genetic variants analyzed do not have a major role in the susceptibility to the development of celiac disease in north-eastern Italian patients, we think that the possible involvement of IL10 gene in CD should deserve further investigation and that large-scale studies are recommended to confirm our findings.
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PMID:Interleukin-10 gene promoter polymorphisms in celiac patients from north-eastern Italy. 2476 47

Celiac disease (CD) is the most common food-sensitive enteropathy in genetically susceptible individuals. The major genetic risk factors known are specific human leukocyte antigen (HLA)-DQ haplotypes, but other genetic factors are supposed to be involved. Interleukin-18 (IL-18) is a pro-inflammatory cytokine that has an important role in the immune defense and it has the potential to influence inflammatory disorders. IL-18 is able to promote Th1 cell development and it is expressed in the mucosa of the small intestine in celiac patients. Given the IL-18 biological role, and since a few studies have previously suggested its involvement in CD, in order to investigate the role of IL18 gene in the susceptibility to CD we have performed a case-control study, analyzing two IL18 gene promoter polymorphisms, previously reported to impair the transcriptional activity of the gene, (-137G > C and -607C > A, rs187238 and rs1946518 respectively). A total of 556 CD Italian patients and 582 controls, further stratified for HLA class II (DQ) CD risk haplotypes were enrolled. The -607A > C A allele and A/A genotype, as well as the combination of this allele with the -137G allele in the AG haplotype, were associated with an increased risk towards CD development, in particular in HLA-DQ2.2 patients. Although the association was very moderate, our results indicate the possible involvement of IL18 gene in the susceptibility to CD, and for this reason we do think it should deserve further investigation.
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PMID:Interleukin-18 gene promoter polymorphisms and celiac disease in Italian patients. 2537 28


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