1,720,985 research outputs found
Is the geographic distribution of HLA-B27 and ankylosing spondylitis the outcome of genetic selection operated by malaria endemic? Clues for this hypothesis
No full textAnalysis of T cell responses to VPAC1 400-408 and homologous peptides from self and microbial proteins in patients with Ankylosing Spondylitis.
No full textHLA Class I or Class II and Disease Association: Catch the Difference If You Can
Full text linkThe association of autoimmune diseases with HLA has been known for many decades. To date, however, the underlying mechanisms have not been fully understood.
The recently introduced genome-wide association studies (GWAS) have suggested that several genes converging in common pathways contribute to the genetic susceptibility in such disorders. Nevertheless, for most autoimmune/autoinflammatory diseases, the HLA genes are by far the strongest risk factors. The basis of some associations has now been elucidated, particularly in those cases in which exogenous factors are involved
Down-modulation of the Vasoactive Intestinal Peptide Receptor 1 correlates with a functional polymorphism in the 3’ UTR region and shows co-occurrence with HLA-B*2705 in Sardinia
No full textA Sardinian patient with ankylosing spondylitis and HLA-B*2709 co-occurring with HLA-B*1403
No full textIdentification of previously unrecognized predisposing factors for ankylosing spondylitis from analysis of HLA-B27 extended haplotypes in Sardinia
No full textObjective. To define the contribution of HLA genes other than HLA-B27 in conferring susceptibility to ankylosing spondylitis (AS), through analysis of HLA-B27 haplotypes in Sardinian subjects. Methods. Ninety-eight patients with AS, 133 HLA-B27-positive controls (of whom 33 were positive for HLA-B*2709), and 190 randomly selected controls were genotyped for microsatellites and single-nucleotide polymorphisms (SNPs) spanning the HLA region. Results. Haplotypes carrying either the B*2705 or the B*2709 allele were found to share a conserved region downstream of the HLA-B gene and a functional polymorphism in the HLA-E gene (W28G), while differing in all other markers. Notably, the presence of an A at SNP rs1264457, encoding for Arg-128, was significantly increased in the cohort of patients (P = 6 x 10(-6), corrected P = 3 x 10(-5)) but not in B*2705- or B*2709-positive controls. Comparing the alleles co-occurring at each HLA marker, we identified a region differentiating patients with AS and B*2705-matched controls. In particular, there was a markedly increased prevalence of heterozygosity at rs1264457 among B27-positive controls (74%, versus 47% in patients and 54% in random controls), suggesting a protective role of G128 in AS. Moreover, other markers around the HLA-B gene were also differentially represented. Conclusion. These results demonstrate a significant difference in the frequency of some HLA markers between AS patients and B*2705-positive controls, which could be attributed to the opposite chromosome. In particular, the differential distribution of a functional polymorphism in the HLA-E gene suggests a possible role of natural killer function in AS pathogenesis
Dynamical Characterization of Two Differentially Disease Associated MHC Class I Proteins in Complex with Viral and Self-Peptides
No full textCD8+T-cell mediated self-reactivity in HLA-B27 context as a consequence of dual peptide conformation
No full textHLA-B*2709 does not predispose for Ankylosing Spondylitis although it differs from B*2705, the most common and AS-associated subtype in different ethnic groups, only for the substitution His116Asp. Therefore, a productive approach to elucidate the molecular mechanisms of the disease could be the comparison of these alleles B*2705 has been shown to display certain self-peptides enriched in basic residues i.e., pVIPR and pGR, in a dual conformation and this is accompanied by the presence of specific cytotoxic T cells in patients with AS. In this study, we convalidate our previous observation that B*2709 healthy subjects do not possess primary reactivity towards pVIPR while showing a prompt CD8+ T cell response driven by pGR. Notably, in the B*2709 context of presentation, pVIPR assumes only a single conformation in contrast with pGR which is dimorphic. These results suggest a possible general connection between the occurrence of double peptide conformation and the property of inducing specific autoimmune responses
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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