Journal ArticleDOI
A combination of a particular HLA-DPβ allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease
Teodorica L. Bugawan,Giovanna Angelini,James W. Larrick,Salvatore Auricchio,Giovanni Battista Ferrara,Henry A. Erlich +5 more
TLDR
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.read more
Citations
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Journal ArticleDOI
Gluten, major histocompatibility complex, and the small intestine: A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’)
TL;DR: The nature and basis of nonresponsive celiac sprue require more thoughtful initiatives to elucidate the immunologic mechanism(s) of unresponsiveness and evaluate possible means of reversal.
Journal ArticleDOI
HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis
Ludvig M. Sollid,Erik Thorsby +1 more
TL;DR: The evidence behind this concept that a particular HLA-DQ heterodimer, encoded by the DQA1*0501 and DQB1*0201 genes in cis or trans configuration, confers the primary disease susceptibility is reviewed.
Journal ArticleDOI
Hla types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the european genetics cluster on celiac disease
Kati Karell,A.S. Louka,S J Moodie,Henry Ascher,F. Clot,Luigi Greco,Paul J. Ciclitira,Ludvig M. Sollid,Jukka Partanen +8 more
TL;DR: The results underline the primary importance of HLA-DQ alleles in susceptibility to celiac disease, and the extreme rarity of celiac patients carrying neither the D Q2 or DQ8 heterodimers nor one half of the DQ2 heterodimer alone.
Journal ArticleDOI
Choosing the greater of two goods: neural currencies for valuation and decision making
TL;DR: A series of recent neurophysiological studies in monkeys has begun to address the challenge of understanding the brain mechanisms that mediate decision making under conditions of uncertainty using novel methods to manipulate and measure an animal's internal valuation of competing alternatives.
Journal ArticleDOI
Flutter discrimination: neural codes, perception, memory and decision making.
Ranulfo Romo,Emilio Salinas +1 more
TL;DR: In this paper, the primary somatosensory cortex drives higher cortical areas where past and current sensory information are combined, such that a comparison of the two evolves into a behavioural decision.
References
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TL;DR: A thermostable DNA polymerase was used in an in vitro DNA amplification procedure, the polymerase chain reaction, which significantly improves the specificity, yield, sensitivity, and length of products that can be amplified.
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Journal ArticleDOI
T cell tolerance by clonal elimination in the thymus
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Journal ArticleDOI
HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus.
TL;DR: Analysis of DNA sequences from diabetics indicates that alleles ofHLA-DQβ determine both disease susceptibility and resistance, and that the structure of the DQ molecule, in particular residue 57 of the β-chain, specifies the autoimmune response against the insulin-producing islet cells.