HLA class II gene frequencies in Crohn's disease: a population based analysis in Germany.

Reinshagen, Max; Loeliger, Cornelius; Kuehnl, P.; Weiß, U.; Manfras, Burkhard; Adler, Guido; Boehm, Bernhard O.

doi:10.1136/gut.38.4.538

Cited by 76 publications

(32 citation statements)

References 19 publications

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“…In other serologic studies, the HLA class II DR1-DQ5 haplotype was found to be associated with CD in Caucasians [12,15,25]. Moreover, recent molecular analyses of the HLA class II genes in Japanese [16,23,24] and Caucasian populations [13,[26][27][28] (including the current study) demonstrated significant HLA class II allele and haplotype associations with IBD.…”

Section: Introductionsupporting

confidence: 65%

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

Trachtenberg¹,

Yang

Hayes³

et al. 2000

Human Immunology

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Ulcerative colitis (UC) and Crohn's disease (CD) are the clinical entities comprising idiopathic inflammatory bowel disease (IBD). Previous studies on the association of IBD and human leukocyte antigen (HLA) class II genes suggested a role for HLA in this disease. Here we present HLA class II (DRB1, DQB1, DQA1, DPB1) allele and haplotype distributions determined using the polymerase chain reaction and sequence-specific oligonucleotide probe methods. A total of 578 UC and CD Caucasian patients and controls from Jewish (Ashkenazi) and non-Jewish populations was examined. Our previously reported association of DR1-DQ5 with CD was attributable to DRB1*0103. A dramatic association with IBD and the highly unusual DRB1*0103-DQA1*0501-DQB1*0301 haplotype (OR = 6.6, p = 0.036) was found. The more common DR1 haplotype, DRB1*0103-DQA1*0101-DQB1*0501, was also associated with IBD (OR = 3.1, p = 0.014), a result suggesting that interaction between DR and DQ may determine the extent of disease risk. Our previously reported association of DR2 with UC was attributable to DRB1*1502 (OR = 2.6, p = 0.006). At the DPB1 locus, a significant association of DPB1*0401 with CD was observed for the combined populations (OR = 1.85, p = 0.007). These observations indicate that some class II alleles and haplotypes confer susceptibility to both UC and CD, implying common immunogenetic mechanisms of pathogenesis, while others confer risk to only one of these diseases, and illustrate the value of DNA HLA typing in disease susceptibility analyses.

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Section: Introductionsupporting

confidence: 65%

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

Trachtenberg¹,

Yang

Hayes³

et al. 2000

Human Immunology

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“…The up-regulation of antigen presentation genes is consistent with increased expression of HLA Class II molecules that typically occurs in IBD in humans [29]. HLA Class II genes have been associated with risk of IBD in a number of populations [30,31] (reviewed in ref. [32]).…”

Section: Discussionmentioning

confidence: 83%

Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acid- and arachidonic acid-enriched diets

Roy

Barnett

Knoch

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acidand arachidonic acid-enriched diets AbstractIn vivo models of Inflammatory Bowel Diseases (IBD) elucidate important mechanisms of chronic inflammation. Complex intestinal responses to food components create a unique "fingerprint" discriminating health from disease. Five-week-old IL10−/− and C57BL/6J (C57; control) mice were inoculated orally with complex intestinal microflora (CIF) and/or pure cultures of Enterococcus faecalis and E. faecalis (EF) aiming for more consistent inflammation of the intestinal mucosa. Inoculation treatments were compared to noninoculated IL10−/− and C57 mice, either kept in specific pathogen free (SPF) or conventional conditions (2×5 factorial design). At 12 weeks of age, mice were sacrificed for intestinal histological (HIS) and transcriptomic analysis using limma and Ingenuity Pathway Analysis Software. Colonic HIS was significantly affected (P < 0.05) in inoculated IL10−/− mice and accounted for approximately 60% of total intestinal HIS. Inoculation showed a strong effect on colonic gene expression, with more than 2000 genes differentially expressed in EF·CIF-inoculated IL10−/− mice. Immune response gene expression was altered (P < 0.05) in these mice. The second study investigated the effect of arachidonic (AA) and eicosapentaenoic acid (EPA) on colonic HIS and gene expression to test whether EPA, contrary to AA, diminished intestinal inflammation in EF·CIF IL10−/− mice (2×4 factorial design). AIN-76A (5% corn oil) and AIN-76A (fat-free) +1% corn oil supplemented with either 3.7% oleic acid (OA), AA or EPA were used. IL10−/− mice fed EPA-and AAenriched diets had at least 40% lower colonic HIS (P < 0.05) than those fed control diets (AIN-76A and OA diets). The expression of immune response and 'inflammatory disease' genes (down-regulated: TNF, IL6, S100A8, FGF7, PTGS2; up-regulated: PPAR, MGLL, MYLK, PPSS23, ABCB4 with EPA and/or AA) was affected in IL10−/−mice fed EPA-and AA-enriched diets, compared to those fed AIN-76A diet. AbstractIn vivo models of Inflammatory Bowel Diseases (IBD) elucidate important mechanisms of chronic inflammation. Complex intestinal responses to food components create a unique "fingerprint" discriminating health from disease. Five-week-old IL10 −/− and C57BL/6J (C57; control) mice were inoculated orally with complex intestinal microflora (CIF) and/or pure cultures of Enterococcus faecalis and E. faecalis (EF) aiming for more consistent inflammation of the intestinal mucosa. Inoculation treatments were compared to non-inoculated IL10 −/− and C57 mice, either kept in specific pathogen free (SPF) or conventional conditions (2 × 5 factorial design). At 12 weeks of age, mice were sacrificed for intestinal histological (HIS) and transcriptomic analysis using limma and Ingenuity Pathway Analysis Software. Colonic HIS was significantly affected (P < 0.05) in inoculated IL10 −/− mice and accounted for approximately 60% of total ...

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“…Earlier CD onset was associated with more frequent CD flares, 59 a positive family history, 60 positive tests for antiSaccharomyces cervisiae antibodies, 61 presence of HLA DR7, 62 extensive jejunal and ileal involvement with CD, 63 upper gastrointestinal involvement, 64 and a need for at least one surgical procedure. 64 65 Presence of epithelioid granulomas in CD patients was strongly associated with a higher rate of postoperative recurrence (that is, with a need for two surgical procedures).…”

mentioning

confidence: 99%

Frequency and significance of granulomas in a cohort of incident cases of Crohn's disease

Héresbach

2005

Gut

137

102

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Background and aims: Epithelioid granulomas is one of the best histological criterion for distinguishing Crohn's disease (CD) from other inflammatory bowel diseases. Few data are available on the time of occurrence of epithelioid granulomas, and the value of epithelioid granulomas in predicting outcome has been determined only in cohorts of prevalent CD cases. Our objective was to evaluate epithelioid granuloma occurrence in incident CD cases and to examine the associations between epithelioid granulomas and outcome. Patients and methods: We reviewed the histological reports of endoscopic and surgical specimens in a cohort of 188 consecutive incident CD cases seen in 1994 and 1995, and recorded the occurrence of epithelioid granulomas, isolated giant cells, and microgranulomas. Kaplan-Meier curves were plotted for time from CD diagnosis to immunosuppressive treatment or surgery, and associations between epithelioid granulomas and outcome were evaluated in a multivariate analysis. Follow up was at least five years. Results: Granulomas were found in 69 (37%) patients, including 46 (25%) at presentation. Median time from CD diagnosis to epithelioid granuloma detection was 0.16 (0-63) months overall, and 9.59 (0.1-63) months in 23 patients who became epithelioid granuloma positive during follow up. Isolated giant cells were found in 6% of patients and microgranulomas in 12%. Epithelioid granuloma detection increased with the number of endoscopic sampling procedures; sampling site had no influence. By multivariate analysis, epithelioid granulomas were associated with surgical resection but not immunosuppressive therapy. Conclusions: Epithelioid granulomas may separate CD into two pathological subsets and may indicate aggressive disease.

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HLA class II gene frequencies in Crohn's disease: a population based analysis in Germany.

Abstract: Background-Ulcerative colitis

Cited by 76 publications

References 19 publications

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: Transcriptomic analysis of the effects of eicosapentaenoic acid- and arachidonic acid-enriched diets

Frequency and significance of granulomas in a cohort of incident cases of Crohn's disease

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