VAV1 Regulates Experimental Autoimmune Arthritis and Is Associated with Anti-CCP Negative Rheumatoid Arthritis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Genes and Immunity Année : 2017

VAV1 Regulates Experimental Autoimmune Arthritis and Is Associated with Anti-CCP Negative Rheumatoid Arthritis

A.O. Guerreiro-Cacais
  • Fonction : Auteur
U. Norin
  • Fonction : Auteur
A. Gyllenberg
  • Fonction : Auteur
R. Berglund
  • Fonction : Auteur
A.D. Beyeen
  • Fonction : Auteur
G.J. Fournié
  • Fonction : Auteur
R. Holmdahl
  • Fonction : Auteur
L. Alfredsson
  • Fonction : Auteur
L. Klareskog
  • Fonction : Auteur
I. Kockum
  • Fonction : Auteur
L. Padyukov
  • Fonction : Auteur

Résumé

Rheumatoid arthritis (RA) patients can be stratified into two subgroups defined by the presence or absence of antibodies against citrullinated circular peptides (anti-CCP) with most of the genetic association found in anti-CCP positive RA. Here we addressed the role of VAV1, previously associated to multiple sclerosis (MS), in the pathogenesis of RA in experimental models and in a genetic association study. Experimental arthritis triggered by pristane or collagen type II was induced in DA rats and in the DA.BN-R25 congenic line that carries a polymorphism in Vav1. Difference in arthritis severity was observed only after immunization with pristane. In a case-control study, 34 SNPs from VAV1 locus were analyzed by Immunochip genotyping in 11475 RA patients (7573 anti-CCP positive and 3902 negative) and 15,870 controls in six cohorts of European Caucasians. A combination of the previous MS-associated haplotype and two additional SNPs was associated with anti-CCP negative RA (alleles G-G-A-A of rs682626-rs2546133-rs2617822-rs12979659, OR=1.13, P=1.27 × 10 -5). The same markers also contributed to activity of RA at baseline with the strongest association in the anti-CCP negative group for the rs682626-rs12979659 G-A haplotype (β=-0.283, P=0.0048). Our study suggests a role for VAV1 and T-cell signaling in the pathology of anti-CCP-negative RA. © 2017 Macmillan Publishers Limited, part of Springer Nature.
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Dates et versions

hal-02084423 , version 1 (29-03-2019)

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Citer

A.O. Guerreiro-Cacais, U. Norin, A. Gyllenberg, R. Berglund, A.D. Beyeen, et al.. VAV1 Regulates Experimental Autoimmune Arthritis and Is Associated with Anti-CCP Negative Rheumatoid Arthritis. Genes and Immunity, 2017, 18 (1), pp.48--56. ⟨10.1038/gene.2016.49⟩. ⟨hal-02084423⟩
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