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P078 A genetic variant of IL-32 is associated with the ex vivo cytokine production of ANTI-TNF treated pbmcs isolated from rheumatoid arthritis patients
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  1. C Popa1,2,
  2. M Damen3,
  3. K Schraa3,
  4. L Tweehuysen2,
  5. A den Broeder2,
  6. M Netea3,
  7. L Joosten3
  1. 1Rheumatology, Radboud UMC
  2. 2Rheumatology, Sint Maartenskliniek
  3. 3Internal Medicine, Radboud UMC, Nijmegen, Netherlands

Abstract

Introduction Since the introduction of biologics in the treatment of rheumatoid arthritis (RA) disease outcome improved. Still, about 40% of RA patients do not respond to therapy with TNFα blockers. Previously, a strong link between TNFα and interleukin (IL)−32 has been reported in RA.1

Objectives We hypothesise that a promoter single nucleotide polymorphism (SNP) in IL-32 can affect clinical responsiveness to anti-TNFα treatment in RA patients, functioning as a new biomarker in treatment of RA.2

Methods Peripheral mononuclear cells (PBMCs) from RA patients and healthy individuals were stimulated with RPMI or recombinant human (rh)TNFα to study the mRNA and protein expression of IL-32 and other pro-inflammatory cytokines. Moreover, disease activity scores (DAS28), ‘in vitro response’ and clinical response to anti-TNFα therapy (etanercept, adalimumab), of RA patients were measured and all were stratified for the IL-32 SNP (C/T).

Results Stimulation of PBMCs from RA patients was followed by higher IL-32 protein production and a tendency towards higher IL-32β and IL-32γ mRNA expression compared to healthy individuals. When data was stratified for the IL-32 promoter SNP, patients bearing the CC genotype showed higher IL-32 protein expression. Of interest, these patients also produced more cytokines. Even though the DAS28 did not depend on the presence of the promoter SNP, the ‘ex vivo’ cytokine response did have a different pattern in clinical responders depending on the genotype.

Conclusions IL-32 mRNA and protein production was higher in RA patients compared to healthy individuals, with a trend towards higher concentrations in patients bearing the CC genotype. Regardless of the fact that the promoter SNP was not associated with disease activity, IL-1 beta production in the CC-genotype might predict clinical response to either etanercept or adalimumab.

References

  1. . Heinhuis B, et al. Ann Rheum Dis2011;70:660–7.

  2. . Damen MS, et al. Sci Rep2017;7:41629.

Disclosure of interest None declared

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