Gene expression analysis of vascular pathophysiology related to anti-TNF treatment in rheumatoid arthritis

OBJECTIVES: Impaired vascular pathophysiology and increased cardiovascular (CV) mortality are associated with rheumatoid arthritis (RA). To date, no genomic analysis of RA- and RA treatment-related vascular pathophysiology has been published. In this pilot study, we performed gene expression profiling in association with vascular pathophysiology in RA patients. METHODS: Sixteen and 19 biologic-naïve RA patients were included in study 1 and study 2, respectively. In study 1, genetic signatures determined by microarray were related to flow-mediated vasodilation (FMD), pulse-wave velocity (PWV), and common carotid intima-media thickness (IMT) of patients. In study 2, clinical response (cR) vs non-response (cNR) to 1-year etanercept (ETN) or certolizumab pegol (CZP) treatment, as well as “vascular” response (vR) vs non-response (vNR) to biologics, were also associated with genomic profiles. Multiple testing could not be performed due to the relatively small number of patients; therefore, our pilot study may lack power. RESULTS: In study 1, multiple genes were up- or downregulated in patients with abnormal vs normal FMD, IMT, and PWV. In study 2, there were 13 cR and 6 cNR anti-tumor necrosis factor (TNF)-treated patients. In addition, 10, 9, and 8 patients were FMD-20%, IMT-20%, and PWV-20% responders. Again, vascular responder status was associated with changes of the expression of various genes. The highest number of genes showing significant enrichment were involved in positive regulation of immune effector process, regulation of glucose transport, and Golgi vesicle budding. CONCLUSION: Differential expression of multiple genetic profiles may be associated with vascular pathophysiology associated with RA. Moreover, distinct genetic signatures may also be associated with clinical and vascular responses to 1-year anti-TNF treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1862-6) contains supplementary material, which is available to authorized users.