HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

Brown, Matthew A.; Pile, K; Kennedy, L G; Calin, Andrei; Darke, C.; Bell, James B.; Wordsworth, B P; Cornélis, François

doi:10.1136/ard.55.4.268

Cited by 229 publications

(156 citation statements)

References 14 publications

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“…Yet it is common in Caucasian populations, with a 9.4% UK prevalence [2], with HLA-B*2705 the commonest molecular subtype. One possible explanation for this observation is that, through its function in presenting antigenic peptides to CTL, it might offer a protective advantage against pathogens compared with other HLA alleles.…”

Section: Introductionmentioning

confidence: 99%

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

et al. 2005

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We have solved the crystal structures of three HLA‐B*2705–peptide complexes with the immunodominant viral peptides: EBV EBNA3C 258–266 (RRIYDLIEL), influenza (flu) nucleoprotein NP383–391 (SRYWAIRTR), and HIV gag 264–273 (KRWIILGLNK). Long‐term non‐progression during HIV infection has been associated with presentation by HLA‐B*2705, and T cell recognition, of the highly immunodominant KRWIILGLNK peptide. The tight hydrogen‐bonding network observed between the HLA‐B*2705 B‐pocket and the peptide P2 arginine guanadinium anchor explains why mutation of this residue during HIV infection results in loss of peptide binding, immune escape and progression to AIDS. Prominent, solvent‐exposed structures within these peptides may participate in generating T cell responses to these immunodominant epitopes. In the HLA‐B*2705 complex with flu NP383–391, the amino acid side chains of residues 4, 7 and 8 are solvent‐exposed whilst in the HIV decamer, the main‐chain bulges into the solvent around P7. Thus, HLA‐B*2705 presents viral peptides in a range of conformations. Tetrameric complexes of HLA‐B*2705 with the HIV and flu but not EBV peptides bound strongly to the killer‐Ig‐like receptor (KIR)3DL1. Substitution of EBV P8 glutamate to threonine allowed recognition by KIR3DL1. In the HLA‐B*2705–EBV structure the P8 glutamate side chain is solvent‐exposed and may inhibit KIR3DL1 binding through electrostatic forces.See accompanying Commentary: http://dx.doi.org/10.1002/eji.200425875

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Section: Introductionmentioning

confidence: 99%

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

et al. 2005

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“…12 In each of the three positive reports, the 12-repeat allele was by far the most common allele in both cases and controls, and the association with bipolar disorder, while significant, was of relatively small magnitude, with an odds ratio of 1.2-3.1 for persons carrying one or two 12-repeat alleles. By comparison, consider that the odds ratios are 170 for HLA-DR2 and narcolepsy 15 or 2.7-11.2 for ApoE4 and Alzheimer disease. 16 All these studies used the population-based association method in which cases and controls are unrelated, although (hopefully) comparable.…”

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confidence: 99%

Serotonin transporter candidate gene studies in affective disorders and personality: promises and potential pitfalls

1998

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While affective and anxiety disorders are substantially heritable, their inheritances are complex and multifactorial. 1 It is therefore unsurprising that such etiologically heterogeneous illnesses have not easily succumbed to genetic methodologies that are further challenged by an imperfect classification system. 2 Nevertheless, investigators continue to behave as if the problems are not insoluble. Association studies of candidate genes have lately held particular appeal, at least partly since this approach connects well with the familiar view that these disorders arise from alterations in particular brain neurochemical systems.The evidence implicating brain serotonin (5-HT) neurotransmission in anxiety and affective disorders is extensive and compelling. 3,4 In the attempt to investigate whether alterations in function of brain 5-HT systems are etiologically associated with these illnesses, attention has focused on polymorphisms in genes encoding components of the serotonergic system. These genes are seen as potential candidates influencing susceptibility, course, or symptoms. Researchers are investigating variants of genes for the 5-HT synthesis pathway, the 5-HT transporter (5-HTT), and several of the numerous 5-HT receptors. Potentially important sequence variations may occur in the coding region of a gene, in gene promoters (which could affect transcription efficiency), and in intronic regions, which, while non-coding, might affect gene expression or distribution of the gene product. Some variants of serotonin system genes are common, consistent with a role in complex, polygenic disorders with relatively high population incidences.The most common research strategy used in association studies, because it is often logistically easiest, is the population-based approach. Such studies compare the frequencies of polymorphic alleles in a group of individuals with a particular psychiatric diagnosis with those in a reference population. The use of this method is now widespread. Although this strategy has important limitations (see below), initial findings have been intriguing enough to spur further research by diverse groups of investigators.A number of reports have described associations between affective disorders and polymorphisms in or near the 5-HTT gene. The 5-HTT is a major modulator

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“…The frequency of HLA-B27 in patients with AS is approximately 94% [64]. In addition to HLA-B27, also HLA-B27 subtypes have been shown to have different incidences and relations with disease onset.…”

Section: Clinical Relation Of Hla-b27 and Asmentioning

confidence: 99%

The relation between ER stress and HLA-B27 misfolding

Yazar¹

2017

Med Res Innov

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Nowadays, understanding complex association among HLA-B27, ER stress pathways and Spondyloarthropathies (SpAs) has been considered to be important situation. Hitherto, many theories have been claimed by researchers in order to explain this association, but HLA-B27 misfolding theory can be the key theory among all theories. HLA-B27 misfolding is related to UPR (Unfolded Protein Response) and EOR (ER Overload Mechanism), since UPR mechanism protect ER homeostasis against misfolded protein and EOR system provide normal ER function to work on accumulating protein. On the other hand, ER associated degradation (ERAD) degrades unfolded or misfolded proteins which are re-translocated to cytosol for degradation. Present work aims to summarize the main pathways of UPR and ERAD, and then to reveal the relation between the tendency of HLA-B27 to misfold, ER stress and SpAs, especially Ankylosing Spondylitis (AS).

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HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

Abstract: Objective-To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. Methods-HLA-B27 and -B60 typing was performed in 284 white patients with AS.

Cited by 229 publications

References 14 publications

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

Serotonin transporter candidate gene studies in affective disorders and personality: promises and potential pitfalls

The relation between ER stress and HLA-B27 misfolding

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