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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Michelle S. M. A. Damen, Kiki Schraa, Lieke Tweehuysen, Alfons A. den Broeder, Mihai G. Netea, Calin D. Popa, Leo 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 beta production might predict clinical response to etanercept/adalimumab. This indicates that IL-32 could play a role in predicting response to treatment in RA. More... »

PAGES

14050

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-32485-0

DOI

http://dx.doi.org/10.1038/s41598-018-32485-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1106971250

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30232372


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