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AB0762 Clinical Associations of the IL-17A, IL-17F and Nfkb-1 Gene Polymorphisms in Patients with Rheumatoid and Psoriatic Arthritis
  1. R. Sokolik1,
  2. J. Świerkot1,
  3. K. Gębura2,
  4. B. Wysoczańska2,
  5. M. Bielańska2,
  6. L. Korman1,
  7. P. Wiland1,
  8. K. Bogunia-Kubik2
  1. 1Department of Rheumatology, Medical University
  2. 2Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocł aw, Poland

Abstract

Background The pro-inflammatory cytokines IL-17A and IL-17F, primarily produced by Th17 cells, has been shown to be involved in all stages of the autoimmune and inflammatory diseases [1]. Th17 cells are thought to play an important role in rheumatoid (RA) and psoriatic arthritis (PsA) [2].

Objectives The present study aimed to determine the association between their polymorphic variants with possible involvement in disease susceptibility and effect on disease progression in patients with PsA and RA susceptibility, progression and response to therapy with TNF-alpha inhibitors.

Methods Eighty-nine RA and 54 PsA patients and 126 healthy individuals were investigated and genotyped for the IL-17A (rs2275913; G-197A), IL-17F (rs763780; A7488G; His161Arg) and transcription nuclear factor NFkB-1 (rs28362491; -94 ins/del ATTG) alleles.

Results Female RA patients carrying the IL-17A wild type genotype more frequently presented with radiographic changes grade 4 (Steinbrocker) (8/24 vs. 6/47, p=0.058) and were characterized by more active disease after 3 months of therapy with the TNF inhibitors (12/23 vs. 15/45, p=0.040). The presence of the IL-17F minor (G) variant (OR=3.97, p<0.001) and its homozygosity (OR=29.62, p<0.001) was more frequent among RA patients than healthy individuals.

The NFkB1 del genotype was more frequently observed in patients with PsA onset over 40 year of age (16/20 vs. 8/17, p=0.047). PsA patients lacking this NFkB1 del/del genotype (ins positive cases) more frequently presented with severe disease (PASI >10, BSA >10, more than five swollen and tender joints) and subjected to anti-TNF-alpha therapy (20/21 vs. 12/18, p=0.035).

Conclusions These results suggest that the IL-17A and IL-17F polymoprhisms play a significant role in RA while NFkB-1 variants seem to affect PsA.

References

  1. Miossec P, Kolls JK. Targeting IL-17 and TH 17 cells in chronic inflammation. Nat Rev Drug Discov 2012; 11:763:776

  2. Shen H., Goodal JC, Hill Ga ston JS. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spodylitis and rheumatoid arthritis. Arthritis Rheum 2009; 60:1647-1656.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.5856

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