Genetic variant in IL-32 is associated with the ex vivo cytokine production of anti-TNF treated PBMCs from rheumatoid arthritis patients

Scientific Reports
Michelle S M A DamenLeo A B Joosten

Abstract

About 60% of RA patients don't achieve good response with biological disease-modifying anti-rheumatic drugs bDMARD treatment (including TNF inhibitors, TNFi's). Previously, a link between TNFα and interleukin (IL)-32 was reported in RA. However, the exact mechanism linking IL-32 to response to treatment as not been studied yet. Therefore, we explored the influence of a promoter single nucleotide polymorphism (SNP) rs4786370 in IL-32 on clinical responsiveness to TNFi's in RA patients, potentially serving as new biomarker in RA. Expression of pro-inflammatory cytokines by peripheral mononuclear cells (PBMCs) from RA patients and healthy individuals were studied. Moreover, "ex vivo response" and clinical response to anti-TNFα therapy (etanercept, adalimumab) were measured and stratified for the IL-32 SNP. Higher IL-32 protein production was observed in RA patients. Additionally, patients bearing the CC genotype showed higher IL-32 protein and cytokine expression. DAS28 was independent of the promoter SNP, however, the "ex vivo" cytokine response was not. IL-32 mRNA and protein production was higher in RA patients, with a trend towards higher concentrations in patients bearing the CC genotype. Furthermore, genotype dependent IL-1 ...Continue Reading

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Citations

Jun 18, 2021·Journal of Medical Virology·Shuo ZhengXiaoping Huang
Aug 5, 2021·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·Fatemeh MazlumYousef Bakhshizadeh Ghashti
Nov 21, 2021·Journal of Clinical Laboratory Analysis·Susu JinMinghua Jiang

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Methods Mentioned

BETA
biopsies
density gradient centrifugation
ELISA

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