Pathogenesis of giant cell arteritis: More than just an inflammatory condition?

Ly, Kim-Heang; Régent, Alexis; Tamby, Mathieu C.; Mouthon, Luc

doi:10.1016/j.autrev.2010.05.002

Cited by 106 publications

(74 citation statements)

References 142 publications

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“…1,2 It is characterized by inflammatory damage of large-and medium-sized arteries, particularly the extracranial branches of the carotid artery, which can lead to severe complications such as blindness or cerebrovascular events. 3,4 During the last decade, genetic association studies have described several genes that are associated with predisposition to GCA, including genes of immune/inflammatory pathways and genes of the human leukocyte antigen (HLA) class I and II regions. The HLA-DRB1*04 alleles seem to be the most consistently associated genetic risk factors for this form of vasculitis.…”

Section: Introductionmentioning

confidence: 99%

A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

Carmona¹,

McDermott²,

Martin³

et al. 2015

The American Journal of Human Genetics

147

102

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We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1(∗)04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10(-43)) and HLA-DQα1 47 (p = 4.02 × 10(-46)), 56, and 76 (both p = 1.84 × 10(-45)) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10(-6), OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10(-6), OR = 1.20), and REL (rs115674477, p = 1.10 × 10(-5), OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function.

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Section: Introductionmentioning

confidence: 99%

A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

Carmona¹,

McDermott²,

Martin³

et al. 2015

The American Journal of Human Genetics

147

102

View full text Add to dashboard Cite

show abstract

“…Certains travaux ont aussi décrit une variation cyclique et saisonnière de l'incidence de la maladie, faisant donc évoquer la participation d'un facteur environnemental et notamment infectieux dans le déclenchement de la maladie [15,16]. Il s'agit souvent d'étude cas/témoin qui ont détecté, par PCR ou Hybridation in situ, une augmentation de l'ADN de bactéries ou de virus dans les artères temporales de patients atteints de MH : Cytomégalovirus, Parvovirus B19, Herpès Simplex Virus et Chlamydia pneumoniae [17]. La MH est une panartérite inflammatoire à cellules géantes, non nécrosante, de topographie segmentaire et focale, touchant les artères de gros calibre, préférentiellement les branches de la carotide externe et en particulier l'artère temporale superficielle.…”

Section: Points Essentielsunclassified

Pathogénie de l’artérite à cellules géantes

Samson

Bonnotte

2012

La Presse Médicale

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“…The pathophysiology of giant cell arteritis is still poorly understood but T-cells and dendritic cells play a pivotal role. Dendritic cells activate T-cells that produce TNF-α and other proinflammatory citokines contributing to the activation of macrophages and further recruitment of T cells and macrophages in the inflammatory lesion (Ly et al , 2010). Moreover TNF-α is present in high levels inside temporal artery lesions in patients with giant cell arteritis, particularly in corrispondences to the granulomatous areas (Hernandez-Rodriguez et al, 2004).…”

Section: Giant Cells Arteritismentioning

confidence: 99%