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OP0071 Tnf-Alpha, TNF Receptor, HLA-E and NKG2A Gene Polymorphisms and Response to Anti-TNF-Alpha Treatement in Rheumatoid Arthritis
  1. J. Swierkot1,
  2. M. Iwaszko2,
  3. K. Gebura2,
  4. B. Nowak3,4,
  5. L. Korman1,
  6. K. Kolossa5,
  7. S. Jeka5,
  8. P. Wiland1,
  9. K. Bogunia-Kubik2
  1. 1Rheumatology and Internal Medicine, Medical University Wroclaw
  2. 2Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
  3. 3Department of Pharmacology, Medical University Wroclaw
  4. 4Rheumatology and Internal Medicine, Wroclaw University Hospital, Wroclaw
  5. 5Rheumatology and Connective Tissue Diseases, Hospital University Number 2 Jana Biziela, Bydgoszcz, Poland


Background 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.

Objectives 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.

Methods 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 TNFA promoter (rs1800629 G>A; rs361525 G>A; rs1799724 C>T); TNF receptors (TNFR1A: rs767455 G>A; TNFR1B: rs1061622; T>G) while 89 patients were studied for the HLA-E (rs1264457 C>T; HLA-E*01:01, HLA-E*01:03, A>G) and NKG2A (rs7301582 C>T; rs2734440 A>G) genes using LightSNiP typing or Custom TaqMan® SNP Genotyping Assays.

Results Among polymorphisms located within TNF-alpha and receptors genes only the TNFR1A (rs767455, G>A) and one of the TNFA (rs1799724, C>T) promoter polymorphisms were found to be associated with response to anti-TNF therapy. Significantly more patients with the homozygous TNFR1A AA 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 TNFA T variant (DAS28 – 2.05) compared to the C allele carriers (p=0.045).

As for HLA-E and NKG2A genes, after 3 months of anti-TNF treatment the significantly worse (EULAR DAS28) response was observed in patients carrying the HLA-E C allele (20/45 vs. 9/28, p=0.030), HLA-E*01:03/01:03 genotype (8/10 vs. 30/73, p=0.038), NKG2A-(rs7301582)-CC genotype (28/51 vs. 10/33, p=0.043) or NKG2A-(rs2734440)-AA 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 HLA-E CC genotype (p=0.09). Also treatment failure (inefficiency or loss of effectiveness of therapy) was more frequently observed in the HLA-E CC homozygous patients (5/8 vs. 12/61, p=0.018) as well as in those with the NKG2A-(rs2734440)-AA genotype (15/37 vs. 3/33, p=0.005).

Conclusions 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.

Acknowledgements Supported by the UMO-2012/05/N/NZ5/02607 and 2011/01/B/NZ5/05367 grants from the National Science Center.

Disclosure of Interest 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

DOI 10.1136/annrheumdis-2014-eular.5416

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