AI Article Synopsis
- The study examines the predictive ability of gene expression profiles for response to TNF inhibitors in rheumatoid arthritis, but previous validation efforts fell short for clinical applications.
- RNA sequencing was performed on the most extreme responders and nonresponders from a patient cohort to identify differences in gene expression.
- The results indicated that two genes, GPR15 and SEMA6B, had altered expression levels in nonresponders, but they were influenced more by smoking habits than by TNF inhibitor response.
Article Abstract
Background: Several studies have employed microarray-based profiling to predict response to tumor necrosis factor-alpha inhibitors (TNFi) in rheumatoid arthritis (RA); yet efforts to validate these targets have failed to show predictive abilities acceptable for clinical practice.
Methods: The eighty most extreme responders and nonresponders to TNFi therapy were selected from the observational BiOCURA cohort. RNA sequencing was performed on mRNA from peripheral blood mononuclear cells (PBMCs) collected before initiation of treatment. The expression of pathways as well as individual gene transcripts between responders and nonresponders was investigated. Promising targets were technically replicated and validated in n = 40 new patients using qPCR assays.
Results: Before therapy initiation, nonresponders had lower expression of pathways related to interferon and cytokine signaling, while also showing higher levels of two genes, GPR15 and SEMA6B (p = 0.02). The two targets could be validated, however, additional analyses revealed that GPR15 and SEMA6B did not independently predict response, but were rather dose-dependent markers of smoking (p < 0.0001).
Conclusions: The study did not identify new transcripts ready to use in clinical practice, yet GPR15 and SEMA6B were recognized as candidate explanatory markers for the reduced treatment success in RA smokers.
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| http://dx.doi.org/10.1080/1744666X.2018.1480937 | DOI Listing |
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