Title |
Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis
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Published in |
Genes & Immunity, November 2014
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DOI | 10.1038/gene.2014.62 |
Pubmed ID | |
Authors |
T J Kenna, M C Lau, P Keith, F Ciccia, M-E Costello, L Bradbury, P-L Low, N Agrawal, G Triolo, R Alessandro, P C Robinson, G P Thomas, M A Brown |
Abstract |
The mechanism by which human leukocyte antigen B27 (HLA-B27) contributes to ankylosing spondylitis (AS) remains unclear. Genetic studies demonstrate that association with and interaction between polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 influence the risk of AS. It has been hypothesised that ERAP1-mediated HLA-B27 misfolding increases endoplasmic reticulum (ER) stress, driving an interleukin (IL) 23-dependent, pro-inflammatory immune response. We tested the hypothesis that AS-risk ERAP1 variants increase ER-stress and concomitant pro-inflammatory cytokine production in HLA-B27(+) but not HLA-B27(-) AS patients or controls. Forty-nine AS cases and 22 healthy controls were grouped according to HLA-B27 status and AS-associated ERAP1 rs30187 genotypes: HLA-B27(+)ERAP1(risk), HLA-B27(+)ERAP1(protective), HLA-B27(-)ERAP1(risk) and HLA-B27(-)ERAP1(protective). Expression levels of ER-stress markers GRP78 (8 kDa glucose-regulated protein), CHOP (C/EBP-homologous protein) and inflammatory cytokines were determined in peripheral blood mononuclear cell and ileal biopsies. We found no differences in ER-stress gene expression between HLA-B27(+) and HLA-B27(-) cases or healthy controls, or between cases or controls stratified by carriage of ERAP1 risk or protective alleles in the presence or absence of HLA-B27. No differences were observed between expression of IL17A or TNF (tumour necrosis factor) in HLA-B27(+)ERAP1(risk), HLA-B27(+)ERAP1(protective) and HLA-B27(-)ERAP1(protective) cases. These data demonstrate that aberrant ERAP1 activity and HLA-B27 carriage does not alter ER-stress levels in AS, suggesting that ERAP1 and HLA-B27 may influence disease susceptibility through other mechanisms.Genes and Immunity advance online publication, 6 November 2014; doi:10.1038/gene.2014.62. |
X Demographics
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Japan | 1 | 3% |
Unknown | 34 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 11 | 31% |
Researcher | 6 | 17% |
Professor | 3 | 9% |
Student > Master | 3 | 9% |
Student > Doctoral Student | 2 | 6% |
Other | 7 | 20% |
Unknown | 3 | 9% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 9 | 26% |
Agricultural and Biological Sciences | 7 | 20% |
Biochemistry, Genetics and Molecular Biology | 4 | 11% |
Immunology and Microbiology | 4 | 11% |
Chemistry | 2 | 6% |
Other | 4 | 11% |
Unknown | 5 | 14% |