Association between IL23R and ERAP1 polymorphisms and sacroiliac or spinal MRI inflammation in spondyloarthritis: DESIR cohort data

Abstract Background To investigate the association between 12 single nucleotide polymorphisms (SNPs) located on ERAP1 and IL23R with the presence of inflammation on the sacroiliac joint (SIJ) or spinal magnetic resonance imagery (MRI) in an early onset spondyloarthritis (SpA) cohort. Methods All the patients included in the DESIR cohort with an axial SpA and available DNA at baseline were enrolled in this study (n = 645 patients) and underwent a clinical examination, CRP assay, SIJ and spinal MRI scans. Six SNPs located on ERAP1 (rs30187, rs27044, rs27434, rs17482078, rs10050860, rs2287987) and six SNPs located on IL23R (rs1004819, rs10489629, rs1343151, rs2201841, rs10889677, rs11209032) were genotyped. Univariable analyses were performed to test the association between the genotypes and SIJ and spinal MRI inflammation, as well as disease activity based on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP) and CRP. Results One SNP located on ERAP1 (rs27434) and haplotype CCT of ERAP1 were associated with SIJ inflammation detected by MRI, but these associations were below the Bonferroni corrected threshold of significance. However, one SNP (rs1004819) located on IL23R was associated with SIJ MRI inflammation (rs1004819: TT 42.3%, CT 40.5%, CC 26.5%, p = 0.0005). This locus was also significantly associated with Spondyloarthritis Research Consortium of Canada scores while no association with another inflammatory parameter such as BASDAI, ASDAS-CRP, CRP or Berlin MRI score was identified in this population. Conclusion One locus of the IL23R gene was associated with SIJ MRI inflammation and might be a marker of more active disease in recent onset SpA. Trial registration clinicaltrials.gov, NCTO 164 890

A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients

International audienceBiological disease-modifying anti-rheumatic drugs (bDMARDs) have changed care of patients with rheumatoid arthritis (RA). However, bDMARDs are costly, can lead to serious infections, and induce a sustained remission in only 30% of RA patients. In this study, we sought to determine if the clinical response to treatment with Tocilizumab (TCZ), an IL-6 inhibitor, varied with genetic background. The efficacy of TCZ was assessed using the European League Against Rheumatism (EULAR) response criteria, measured after 3 months of treatment in two samples of French RA patients (TOCI and ROC studies). Single nucleotide polymorphisms (SNPs) in 21 candidate genes were genotyped using KasPar method (LGC-genomics, UK) and then analyzed to determine their contribution to variation in the response to treatment. One hundred twenty-three patients in the TOCI group (79.8%) and 48 patients in the ROC group (80%) experienced good or moderate EULAR response. The clinical response to treatment was associated with SNP genotype in the gene IL6R, with patients with the homozygous AA-genotype for rs12083537 (IL6R) showing a significantly better response than homozygous or heterozygous patients with the G allele [TOCI: 87.5% of responders for AA genotype vs. 72.2% for AG or GG genotype (p = 0.018); ROC patients: 89.2% of responders for AA genotype vs. 65.2% for AG or GG genotype, p = 0.044]. A meta-analysis combining data from the two cohorts confirmed the lower response rate in patients carrying a copy of the G allele (OR (95% CI) = 0.35 (0.16–0.61), p = 0.001). No association was found with any of the other SNPs tested