Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts).

Adeline Ruyssen-Witrand (1, 2) , Cedric Lukas (3) , Delphine Nigon (1) , Karen Dawidowicz (4) , Jacques Morel (3) , Jean Sibilia (5, 6) , Bénédicte Jamard (1) , Anne Cambon-Thomsen (1, 2) , Alain Cantagrel (7, 1) , Philippe Dieudé (8, 9, 4) , Arnaud Constantin (1, 2) , Alain Saraux (10, 11, 12)

1 Centre de Rhumatologie [CHU Toulouse]
2 LEASP - Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps
3 Département de Rhumatologie[Montpellier]
4 Service de rhumatologie [Bichat]
5 Département de Rhumatologie
6 Physiopathologie des arthrites
7 CPTP - Centre de Physiopathologie Toulouse Purpan
8 UPD7 - Université Paris Diderot - Paris 7
9 Immunopathologie rénale, récepteurs et inflammation
10 CIC - Brest - Centre d'Investigation Clinique
11 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
12 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie

To assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.

This work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.

The AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14-3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68-6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94-18.69], p = 0.002) on the risk of erosions in ACPA+ patients.

A haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.

Mots clés: Autoantibodies; Disease progression; IL-2RA; IL-2RB; Rheumatoid arthritis; Single nucleotid polymorphism

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie; Rhumatologie et système ostéo-articulaire

Adeline Ruyssen-Witrand, Cedric Lukas, Delphine Nigon, Karen Dawidowicz, Jacques Morel, et al.. Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts).. Joint Bone Spine, 2014, 81 (3), pp.228-34. ⟨hal-01558258⟩