Major histocompatibility complex susceptibility genes for dermatitis herpetiformis compared with those for gluten-sensitive enteropathy.
A. R. Ahmed,Juan J. Yunis,Deborah Marcus-Bagley,Edmond J. Yunis,Marcela Salazar,Aubrey J. Katz,Zuheir L. Awdeh,Chester A. Alper +7 more
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TLDR
The findings suggest that the MHC susceptibility gene for DH is between class II and complotype regions, closest to the complotype, whereas that for GSE is in the class II region.Abstract:
Dermatitis herpetiformis (DH) shares some clinical features and major histocompatibility complex (MHC) markers with gluten-sensitive enteropathy (GSE). We compared MHC haplotypes in 27 patients with DH, 35 patients with GSE, and normal controls. As in GSE, the frequencies of two extended haplotypes, [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7], were increased in patients with DH. Distributions of fragments of extended haplotypes, consisting of some but not all of the elements of complete extended haplotypes, were analyzed to attempt to localize a susceptibility gene. Besides complete extended susceptibility haplotypes, (DR3, DQ2) and (DR7, DQ2) fragments were most common in GSE. In contrast, DH showed only a few such fragments but many instances of the fragment (SC01). The differences in distribution of these fragments in the two diseases were highly significant (P < 0.002). HLA-DQ2 and DR3 had the highest odds ratios for GSE, but the highest odds ratio for DH was for the complotype SC01. These findings suggest that the MHC susceptibility gene for DH is between class II and complotype regions, closest to the complotype, whereas that for GSE is in the class II region.read more
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The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases
Patricia Price,Campbell S. Witt,Richard J.N. Allcock,David Sayer,Michael J. Garlepp,C.C. Kok,Martyn A. French,Simon Mallal,Frank T. Christiansen +8 more
TL;DR: Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen‐independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH.
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Genetic variations in cytokine expression: a risk factor for severity of adult periodontitis.
TL;DR: The finding that host modifying factors are associated with severe periodontitis suggest a biological mechanism by which some individuals, if challenged by bacterial accumulations, may have a more vigorous immunoinflammatory response, leading to more severe clinical disease.
Journal ArticleDOI
Inheritable variable sizes of DNA stretches in the human MHC: conserved extended haplotypes and their fragments or blocks.
Edmond J. Yunis,Charles E. Larsen,Marcelo Fernandez-Vina,Zuheir L. Awdeh,T. Romero,John A. Hansen,Chester A. Alper +6 more
TL;DR: The concept of the conserved extended haplotype (CEH) is updated using HLA allele identification and TNF microsatellites to show that specific combinations of the four blocks form single genetic units with a total haplotype frequency in the Caucasian population of 0.30.
Journal ArticleDOI
Dermatitis herpetiformis and celiac disease are both primarily associated with the HLA-DQ (α1*0501, (β1*02) or the HLA-DQ (α1*03, (β1*0302) heterodimers
TL;DR: It is concluded that dermatitis herpetiformis and celiac disease are associated to the very same HLA-DQ alpha beta heterodimers.
Journal ArticleDOI
The Haplotype Structure of the Human Major Histocompatibility Complex
Chester A. Alper,Chester A. Alper,Charles E. Larsen,Charles E. Larsen,Devendra P. Dubey,Zuheir L. Awdeh,Dolores A. Fici,Edmond J. Yunis,Edmond J. Yunis +8 more
TL;DR: The results suggest that the human genome, including the major histocompatibility complex (MHC), consists largely of 5- to 200-kb blocks of sequence fixity between which random recombination occurs, and the use of statistical analysis rather than direct haplotype determination and counting fails to reveal the details of haplotype structure essential for gene localization.
References
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An extended HLA-D region haplotype associated with celiac disease
Mark D. Howell,Jennifer R. Smith,Raleigh K. Austin,Dermot Kelleher,Gerald T. Nepom,Brigitte Volk,Martin F. Kagnoff +6 more
TL;DR: 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 that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA -D region.
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Inheritance and influence of histocompatibility (HL-A) antigens in adult coeliac disease
TL;DR: In a study of histocompatibility antigens in adult coeliac disease the HL-A phenotypes have been determined in 117 patients and 149 of their first-degree relatives, of whom 94 had had a jejunal biopsy performed.
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Alterations in HLA-DP and HLA-DQ antigen frequency in patients with dermatitis herpetiformis
TL;DR: A role of HLA-DP region genes or genes closely linked to them may be important in DH either as markers of the disease haplotype or by direct involvement in its pathogenesis.
Journal ArticleDOI
Evidence that the IgA in patients with linear IgA disease is qualitatively different from that of patients with dermatitis herpetiformis.
TL;DR: This study tested the presence of in vivo bound J‐chain in the uninvolved skin of patients with papillary IgA dermatitis herpetiformis and found it to be dimeric and of mucosal origin.