Prevalence of spondyloarthritis in reference to HLA-B27 in the French population: results of the GAZEL cohort

Costantino, Félicie; Talpin, Alice; Said‐Nahal, Roula; Goldberg, Marcel; Henny, Joseph; Chiocchia, Gilles; Garchon, Henri‐Jean; Zins, Marie; Bréban, Maxime

doi:10.1136/annrheumdis-2013-204436

Cited by 98 publications

(58 citation statements)

References 29 publications

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“…It is thus possible that HLA-B27 has a selective developmental or reproductive advantage that maintains its prevalence in multiple human populations despite the almost certain evolutionary disadvantages associated with increased SpA prevalence. Unexpectedly the prevalence of HLA-B27 has been found to decrease with age, suggesting that possession of B27 effects a survival disadvantage after middle age (31). This is an intriguing finding that requires replication in different populations.…”

Section: Other Functions Of Hla-b27 Heterotrimers and Free Heavy Chainsmentioning

confidence: 88%

“…Collectively the SpA, which are listed in Table 1, may affect approximately 0.6-1% of the adult US population (32). AS is the prototypic and most common of the SpA, affecting approximately 0.3% of the adult US population (32) and 0.4% of the adult French population (31). Notably, the prevalence is Acute anterior uveitis Acute sterile inflammation of the anterior chamber of the eye 50 40 Abbreviation: OR, odds ratio.…”

Section: Hla-b27 and Spondyloarthritismentioning

confidence: 97%

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Hla-B27

Bowness

2015

Annu. Rev. Immunol.

218

169

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Possession of the human leukocyte antigen (HLA) class I molecule B27 is strongly associated with ankylosing spondylitis (AS), but the pathogenic role of HLA-B27 is unknown. Two broad theories most likely explain the role of HLA-B27 in AS pathogenesis. The first is based on the natural immunological function of HLA-B27 of presenting antigenic peptides to cytotoxic T cells. Thus, HLA-B27-restricted immune responses to self-antigens, or arthritogenic peptides, might drive immunopathology. B27 can also "behave badly," misfolding during assembly and leading to endoplasmic reticulum stress and autophagy responses. β2m-free B27 heavy chain structures including homodimers (B272) can also be expressed at the cell surface following endosomal recycling of cell surface heterotrimers. Cell surface free heavy chains and B272 bind to innate immune receptors on T, NK, and myeloid cells with proinflammatory effects. This review describes the natural function of HLA-B27, its disease associations, and the current theories as to its pathogenic role.

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Section: Other Functions Of Hla-b27 Heterotrimers and Free Heavy Chainsmentioning

confidence: 88%

Section: Hla-b27 and Spondyloarthritismentioning

confidence: 97%

Hla-B27

Bowness

2015

Annu. Rev. Immunol.

218

169

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“…Nevertheless, SpA has been shown to exist in the absence of HLA-B27 in as many as one-fourth of the patients in a Caucasian population (11). HLA-B27-negative patients differ from HLA-B27-positive patients in that they have a later age at disease onset and less frequently develop radiographic sacroiliitis and uveitis.…”

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confidence: 99%

Editorial: Animal Models of Spondyloarthritis: Do They Faithfully Mirror Human Disease?

Bréban

Araujo

Chiocchia

2014

Arthritis & Rheumatology

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“…Spondyloarthritis (SpA) is a frequent form of chronic inflammatory arthritis, with an estimated lifetime risk of ;0.43% in adult Caucasian populations (1). It comprises several closely related disorders that share clinical and imaging features as well as genetic predisposition (2,3).…”

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confidence: 99%

ERAP1 Gene Expression Is Influenced by Nonsynonymous Polymorphisms Associated With Predisposition to Spondyloarthritis

Costantino

Talpin

Evnouchidou

et al. 2015

Arthritis & Rheumatology

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Objective Several polymorphisms in ERAP1 are strongly associated with susceptibility to spondyloarthritis (SpA). The combination of rs17482078, rs10050860, and rs30187 results in the construction of 3 major haplotypes that are associated with SpA (the “protective” haplotype T/T/C, the “neutral” haplotype C/C/C, and the “susceptibility” haplotype C/C/T). The aim of the present study was to determine whether such haplotypes might affect endoplasmic reticulum aminopeptidase 1 (ERAP‐1) messenger RNA (mRNA) expression, protein level, and/or enzymatic activity in antigen‐presenting cells, a type of cell that is potentially relevant to disease pathogenesis. Methods Monocyte‐derived dendritic cells (DCs) were generated in 2 cohorts (a discovery cohort and a replication cohort) comprising a total of 23 SpA patients and 44 healthy controls. Lymphoblastoid B cell lines were established from individuals who were homozygous for the risk, the neutral, or the protective ERAP1 haplotype, respectively. In those samples, we investigated the relationship between ERAP1 haplotypes and mRNA expression level. We also used Western blot analysis to measure the relative protein expression of ERAP‐1 and a fluorogenic assay to measure its enzymatic activity. Results In monocyte‐derived DCs, there was a strong association between ERAP1 haplotypes and the ERAP‐1 mRNA expression level, with higher levels in subjects harboring the susceptibility haplotype (P = 0.001 and P = 5.6 × 10−7 in the discovery and replication cohorts, respectively). In lymphoblastoid B cell lines, we observed a significant correlation between haplotype risk score and ERAP1 transcript or protein level (P = 0.003, ρ = 0.92 for both). Enzymatic activity followed a similar trend both in monocyte‐derived DCs and in lymphoblastoid B cell lines. Conclusion These data provide strong evidence that SpA‐associated ERAP1 polymorphisms affect the level of gene expression in antigen‐presenting cells. How increased production/activity of ERAP‐1 may influence susceptibility to SpA remains to be determined.

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Prevalence of spondyloarthritis in reference to HLA-B27 in the French population: results of the GAZEL cohort

Abstract: We estimated the prevalence of SpA in the French population in 2010 to 0.43%. With an estimated prevalence of 75.0% in SpA and 6.9% in healthy controls, HLA-B27 increased the disease risk 39-fold, as compared with HLA-B27 negative subjects.

Cited by 98 publications

References 29 publications

Hla-B27

Hla-B27

Editorial: Animal Models of Spondyloarthritis: Do They Faithfully Mirror Human Disease?

ERAP1 Gene Expression Is Influenced by Nonsynonymous Polymorphisms Associated With Predisposition to Spondyloarthritis

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