Close Association of HLA-Bw51 With Behcet's Disease

Ohno, Shigeaki; Ohguchi, M; Hirose, Shunsuke; Matsuda, Hidehiko; Wakisaka, Akemi; Aizawa, Mamoru

doi:10.1001/archopht.1982.01030040433013

Cited by 436 publications

(245 citation statements)

References 12 publications

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“…Amino acids at positions 67, 97, 116, and 152 significantly and independently influenced the risk of developing BD. Oceania, and South America, where expression is low or nil (3,4). Early studies using microsatellite markers in Japanese, Greek, and Italian patients patients with BD showed that HLA-B was the strongest association in each group.…”

supporting

confidence: 41%

HLA-B51* the primary risk in Behçet disease

Wallace

2014

Proc. Natl. Acad. Sci. U.S.A.

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supporting

confidence: 41%

HLA-B51* the primary risk in Behçet disease

Wallace

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…HLA-B*5101 allele expression is associated with Behçet disease [31,32], a multisystemic inflammatory disorder possibly of autoimmune nature [33,34]. The linkage is very suggestive of involvement of peptide presentation function, since Behçet disease is not associated with HLA-B*5201, which differs by only two amino acids located in the pocket B of the peptidebinding groove [34].…”

Section: Discussionsupporting

confidence: 40%

Sampling of Major Histocompatibility Complex Class I-Associated Peptidome Suggests Relatively Looser Global Association of HLA-B*5101 With Peptides

2006

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SummaryWe have analyzed peptides associated with six human MHC class I allomorphs expressed by the U937 cell line. Peptides were isolated by mild acid elution or by MHC class I immunoprecipitation using W6/32 monoclonal antibody. A total of 85 peptides were sequenced by mass spectrometry and their putative binding alleles were assigned using bioinformatic tools. Only three peptides isolated by the two approaches were identical, suggesting that the approaches may yield distinct, partially overlapping peptide populations. Mild acid treatment-derived peptides had overall characteristics suggestive of relatively lower affinity of binding for MHC class I. Interestingly, a large proportion of putative HLA-B*5101-binding peptides was found among the mild-acid treatment eluted peptides, and to a lesser degree in the affinity-purified peptide pool. These results suggest that HLA-B*5101 may bind a potentially large pool of peptides with relatively lower affinity. We suggest that lower affinity of peptide binding may be the basis for inefficient tolerance to HLA-B*5101-binding selfpeptides, a predisposing factor for the development of Behçet disease.

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“…The predominant BD susceptibility locus is the MHC on chromosome 6 (2, 3), which contains the strongest known risk factor for BD, the MHC class I (MHC-I) allele HLA-B*51 (2)(3)(4)(5). Several recent studies have expanded the list of genes or loci implicated in the pathophysiology of BD, which now includes HLA-B, IL10, IL23R, HLA-A, CCR1, STAT4, endoplasmic reticulum amino peptidase 1 (ERAP1), the killer lectinlike receptor cluster on chromosome 12, and, most recently, TLR4 and MEFV (2,3,6,7).…”

mentioning

confidence: 43%

Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity

Ombrello

Kirino

Bakker

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

124

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The HLA protein, HLA-B*51, encoded by HLA-B in MHC, is the strongest known genetic risk factor for Behçet disease (BD). Associations between BD and other factors within the MHC have been reported also, although strong regional linkage disequilibrium complicates their confident disentanglement from HLA-B*51. In the current study, we examined a combination of directly obtained and imputed MHC-region SNPs, directly obtained HLA-B locus types, and imputed classical HLA types with their corresponding polymorphic amino acid residues for association with BD in 1,190 cases and 1,257 controls. SNP mapping with logistic regression of the MHC identified the HLA-B/MICA region and the region between HLA-F and HLA-A as independently associated with BD (P < 1.7 × 10 −8 ). HLA-B*51, -A*03, -B*15, -B*27, -B*49, -B*57, and -A*26 each contributed independently to BD risk. We directly examined rs116799036, a noncoding SNP upstream of HLA-B that was recently suggested to underlie the association of HLA-B*51 with BD, but we were unable to replicate that finding in our collection. Instead, we mapped the BD association to seven MHC class I (MHC-I) amino acid residues, including anchor residues that critically define the selection and binding of peptides to MHC-I molecules, residues known to influence MHC-Ikiller immunoglobulin-like receptor interactions, and a residue located in the signal peptide of HLA-B. The locations of these variants collectively implicate MHC-I peptide binding in the pathophysiology of BD. Furthermore, several lines of evidence suggest a role for altered regulation of cellular cytotoxicity in BD pathogenesis.HLA imputation | autoinflammation | antigen presentation | killer immunoglobulin-like receptors | natural killer cells

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Close Association of HLA-Bw51 With Behcet's Disease

Cited by 436 publications

References 12 publications

HLA-B51* the primary risk in Behçet disease

HLA-B51* the primary risk in Behçet disease

Sampling of Major Histocompatibility Complex Class I-Associated Peptidome Suggests Relatively Looser Global Association of HLA-B*5101 With Peptides

Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity

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Close Association of HLA-Bw51 With Behcet's Disease

Cited by 436 publications

References 12 publications

HLA-B*51 the primary risk in Behçet disease

HLA-B*51 the primary risk in Behçet disease

Sampling of Major Histocompatibility Complex Class I-Associated Peptidome Suggests Relatively Looser Global Association of HLA-B*5101 With Peptides

Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity

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HLA-B51* the primary risk in Behçet disease

HLA-B51* the primary risk in Behçet disease