OP0071 Tnf-Alpha, TNF Receptor, HLA-E and NKG2A Gene Polymorphisms and Response to Anti-TNF-Alpha Treatement in Rheumatoid Arthritis
Authors: J. Swierkot, M. Iwaszko, K. Gebura, B. Nowak, L. Korman, K. Kolossa, S. Jeka, P. Wiland, K. Bogunia-Kubik
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Despite the fact that therapy with TNF-alpha inhibitors constitutes a breakthrough in rheumatoid arthritis (RA) management, no improvement is still achieved in approximately 30% of cases. <h3>Objectives</h3> The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor, and HLA-E and NKG2A receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA. <h3>Methods</h3> For these purpose 280 RA patients who had been treated with TNF-alpha inhibitors for at least 6 months or they stopped therapy because of adverse events were investigated and genotyped for 9 SNPs within the <i>TNFA</i> promoter (rs1800629 G&gt;A; rs361525 G&gt;A; rs1799724 C&gt;T); TNF receptors (<i>TNFR1A</i>: rs767455 G&gt;A; <i>TNFR1B</i>: rs1061622; T&gt;G) while 89 patients were studied for the <i>HLA-E</i> (rs1264457 C&gt;T; HLA-E*01:01, HLA-E*01:03, A&gt;G) and NKG2A (rs7301582 C&gt;T; rs2734440 A&gt;G) genes using LightSNiP typing or Custom TaqMan® SNP Genotyping Assays. <h3>Results</h3> Among polymorphisms located within TNF-alpha and receptors genes only the <i>TNFR1A</i> (rs767455, G&gt;A) and one of the <i>TNFA</i> (rs1799724, C&gt;T) promoter polymorphisms were found to be associated with response to anti-TNF therapy. Significantly more patients with the homozygous <i>TNFR1A AA</i> genotype achieved a good EULAR response at 3 months compared to patients carrying the G allele (p=0.011). At week 24 DAS28 was significantly lower in patients homozygous for the <i>TNFA T</i> variant (DAS28 – 2.05) compared to the C allele carriers (p=0.045). As for <i>HLA-E</i> and <i>NKG2A</i> genes, after 3 months of anti-TNF treatment the significantly worse (EULAR DAS28) response was observed in patients carrying the <i>HLA-E</i><i>C</i> allele (20/45 vs. 9/28, p=0.030), <i>HLA-E*01:03/01:03</i> genotype (8/10 vs. 30/73, p=0.038), <i>NKG2A-</i>(rs7301582)-<i>CC</i> genotype (28/51 vs. 10/33, p=0.043) or <i>NKG2A-</i>(rs2734440)-<i>AA</i> genotype (15/26 vs. 15/50, p=0.026). At week 12 low disease activity or remission was not observed in any of the patients with the <i>HLA-E</i><i>CC</i> genotype (p=0.09). Also treatment failure (inefficiency or loss of effectiveness of therapy) was more frequently observed in the <i>HLA-E</i><i>CC</i> homozygous patients (5/8 vs. 12/61, p=0.018) as well as in those with the <i>NKG2A-</i>(rs2734440)-<i>AA</i> genotype (15/37 vs. 3/33, p=0.005). <h3>Conclusions</h3> These results imply that the polymorphisms within genes coding for TNF-alpha and its TNFR1 receptor as well as HLA-E and NKG2A affect the response to anti-TNF therapy in patients with RA. <h3>Acknowledgements</h3> Supported by the UMO-2012/05/N/NZ5/02607 and 2011/01/B/NZ5/05367 grants from the National Science Center. <h3>Disclosure of Interest</h3> J. Swierkot Grant/research support: UMO-2012/05/N/NZ5/02607 and 2011/01/B/NZ5/05367, M. Iwaszko Grant/research support: UMO-2012/05/N/NZ5/02607 and 2011/01/B/NZ5/05367, K. Gebura Grant/research support: UMO-2012/05/N/NZ5/02607 and 2011/01/B/NZ5/05367, B. Nowak Grant/research support: UMO-2012/05/N/NZ5/02607 and 2011/01/B/NZ5/05367, L. Korman Grant/research support: UMO-2012/05/N/NZ5/02607 and 2011/01/B/NZ5/05367, K. Kolossa: None declared, S. Jeka: None declared, P. Wiland: None declared, K. Bogunia-Kubik Grant/research support: UMO-2012/05/N/NZ5/02607 and 2011/01/B/NZ5/05367 <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5416