Major histocompatibility complex susceptibility genes for dermatitis herpetiformis compared with those for gluten-sensitive enteropathy.
01 Dec 1993-Journal of Experimental Medicine (Rockefeller University Press)-Vol. 178, Iss: 6, pp 2067-2075
TL;DR: 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.
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01 Jan 1998
TL;DR: In this paper, the authors proposed a solution to the problem of finding the minimum number of items in a set of DQs using the HLAAB test set, where the number of players is defined as the sum of all the items in the set.
Abstract: Bu calisma, toplumumuzdaki colyakli cocuklarda karaciger tutulumu ve antigliadin antikor duzeyi ile doku gruplari arasindaki iliskiyi arastirmak icin planlandi. Arastirmaya Cerrahpasa Tip Fakultesi Cocuk Gastroenterolojisi Bilim Dali'nda izlenmekte olan colyak hastaligi tanili 30 hasta alindi. Hastalarin 20'si kiz, 10'u erkek olup yas ortalamasi 5.8 yas idi. Doku tipi olarak HLAAB, DR, DQ antijenleri lenfositotoksisite yontemi ile arastirildi. Tani konma yasi iki yasin altinda olup antigliadin Ig => 50 AU olan hastalarda HLAA32, B16, B5, DQ4, DQ6(1) ve DR14(6) doku gruplarina rastlanmadi. Iki yasin uzerinde olup antigliadin Ig > 50 AU olan hastalarda ise HLAB4'un daha sik, HLADR7'nin ise daha az olmasi anlamli bulundu. Iki yasin uzerinde olup antigliadin IgG>50 AU olan hastalarda ise HLAA1, .A9, B17, B37, B73 ve DR9 doku gruplarinin olmamasi dikkat cekici bulundu. HLAA11, B 18, B40 ve DQ1 iceren colyakli hastalarda anlamli olarak aspartat aminotransferaz yuksekligine, HLAA19, B18 ve B44(12) iceren hastalarda ise anlamli olarak alanin aminotransferaz yuksekligine rastlanmadi. Sonuc olarak doku gruplari ile transaminazlar ve antigliadin duzeyleri arasinda bir iliski bulunmakla beraber, bu sonuclarin baska prospektif calismalarla da desteklenmesinin yararli olacagi dusunuldu.
References
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TL;DR: Electrophoretic studies of fragments from defined types of GBG suggested that GBG cleavage induced by complement or properdin activation in serum occurred through this C moiety, since two variants were detectable in one fragment and two were found in the other fragment.
Abstract: Extensive polymorphism of glycine-rich beta-glycoprotein (GBG) was found in human sera. In all instances, GBG consisted of at least five components on electrophoresis. Patterns were such that they provided evidence for four alleles (at a locus designated Gb) which were expressed as autosomal codominant traits. Gb(S) and Gb(F) were found in all populations but with different frequencies, Gb(F1) was found in Negroes, and Gb(S1) was found in Caucasians. From electrophoretic studies of GBG, evidence was obtained that suggested that the GBG molecule was a tetramer consisting of A and B subunits in a proportion of about 1.6:1. The genetically controlled differences in GBG embodied in the Gb system indicated the presence of a third moiety of the molecule (C), possibly a polypeptide subunit. Electrophoretic studies of fragments from defined types of GBG suggested that GBG cleavage induced by complement or properdin activation in serum occurred through this C moiety, since two variants were detectable in one fragment and two were found in the other fragment. On comparison of fetal-maternal Gb types, approximately one-half the pairs showed differences. This indicated that GBG did not cross the placental barrier.
489 citations
TL;DR: Close linkage with no crossovers was found between the two C4 loci, allowing the definition of C4AB haplotypes, and between C4 haplotypes and the C2 and BF loci of the human histocompatibility complex.
Abstract: Human fourth component of complement (C4) was found to be highly polymorphic by agarose gel electrophoresis of neuraminidase-treated plasma. The system allows clear-cut separation of the products of the two C4 genetic loci, C4A (acidic or Rodgers) and C4B (basic or Chido). There are at least six structural variants and a deletion allele at the C4A locus and two structural variants and a deletion allele at the C4B locus. Close linkage with no crossovers was found between the two C4 loci, allowing the definition of C4AB haplotypes, and between C4 haplotypes and the C2 and BF loci of the human histocompatibility complex. Nine C4 haplotypes, each with a frequency of 0.005 or more in Caucasians, were found. These studies provide direct evidence for two distinct but closely linked genetic loci for human C4 in the major histocompatibility complex on the short arm of chromosome 6.
457 citations
TL;DR: Structural variation in the second component of human complement was identified in about 4% of serum samples from random unrelated individuals of all the major races and suggestive evidence for close linkage between C2 and Bf was obtained.
Abstract: Structural variation in the second component of human complement was identified in about 4% of serum samples from random unrelated individuals of all the major races. Three forms of C2 have been identified by isoelectric focusing in polyacrylamide gel and development of patterns in agarose gel containing antibody-sensitized sheep red cells and C2-deficient serum: C2 C (common), C2 A (acidic), and C2 B (basic). The C2 variants were shown to be inherited as autosomal codominant traits, and suggestive evidence for close linkage between C2 and Bf was obtained.
216 citations
TL;DR: A new DNA-based method of HLA-DP typing is used to analyse the distribution of DPβ alleles in a group of coeliac disease patients and healthy controls and suggests that the polymorphic residues at position 69 and at 56 and 57 may be critical in conferring susceptibility.
Abstract: COELIAC disease is an autoimmune disease of the intestinal mucosa, elicited by ingestion of wheat gluten in genetically susceptible individuals1. Susceptibility to coeliac disease has been associated with the serologically defined variants DR3 and DR7 of the class II antigens encoded by the HLA-D region2,3. Three related class II antigens, each consisting of an alpha and a beta glycoprotein chain, have been identified and are designated HLA-DR, HLA-DQ, and HLA-DP. These highly polymorphic transmembrane proteins bind peptides derived from the processing of foreign antigens4–8 and present them to T lymphocytes; they also influence the specificity of the mature T-cell repertoire9–12. The role of HLA-DP polymorphism in susceptibility has not been as fully explored as that of the other class II antigens because of the complexity of the primed lymphocyte typing (PLT) method for determining DPw specificities13–15. Here we use a new DNA-based method of HLA-DP typing16 to analyse the distribution of DPβ alleles in a group of coeliac disease patients and healthy controls. Two specific DPβ alleles (DPB4.2 and DPB3) are increased in the patient population. Comparison of the DPβ sequences suggests 470 that the polymorphic residues at position 69 and at 56 and 57 may be critical in conferring susceptibility. Further, the contribution of the susceptible DPβ alleles appears to be independent of linkage to the previously reported DR3 and DR7 markers for coeliac disease. The distribution of DQα and β alleles in patients suggests that a specific DQ heterodimer may be responsible for the observed DR associations. Individuals with both this DQ antigen and a specific DPβ allele are at increased risk for coeliac disease.
201 citations
TL;DR: Since the disease is entirely attributable to the presence of an antibody to an intraepidermal intercellular cement substance, it is likely that the class II susceptibility gene (on HLA-B38, SC21, DR4, DQw8, or their segments, in Jewish patients) controls the production of the antibody as a dominantly expressed immune response gene.
Abstract: Of 26 Ashkenazi Jewish patients with pemphigus vulgaris, 24 (92.3%) carried the major histocompatibility complex (MHC) class II alleles HLA-DR4, DQw3, of which all were of the subtype DR4, DQw8. From studies of the patients and their families, haplotypes were defined. It was found that, of the patients who carried HLA-DR4, DQw8, 75% carried one or the other (and in one case, both) of two haplotypes [HLA-B38, SC21, DR4] or HLA-B35, SC31, DR4. The former is a known extended haplotype among normal Jews, with a frequency of 0.102, and the latter may also be an extended haplotype in this ethnic group, with a frequency of 0.017 among normal haplotypes from Jews. Of the remaining DR4-positive patients, all but one had a presumed D-region segment (defined as SC21, DR4, DQw8 or SC31, DR4, DQw8 with variable HLA-B) of these haplotypes. Only one patient had DR4, DQw8 without any other markers of the extended haplotypes. The number of homozygotes and heterozygotes for DR4, DQw8 was consistent with dominant but not recessive (P less than 0.01) inheritance of a class II or a class II-linked susceptibility gene for the disease. Since the disease is entirely attributable to the presence of an antibody to an intraepidermal intercellular cement substance, it is likely that the class II susceptibility gene (on [HLA-B38, SC21, DR4, DQw8], HLA-B35, SC31, DR4, DQw8, or their segments, in Jewish patients) controls the production of the antibody as a dominantly expressed immune response gene.
200 citations