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

Szilárd Póliska, Timea Besenyei, Edit Végh, Attila Hamar, Anita Pusztai, Andrea Váncsa, Nóra Bodnár, Szilvia Szamosi, Mária Csumita, György Kerekes, Zoltán Szabó, Zoltán Nagy, Gabriella Szucs, Sándor Szántó, Gábor Zahuczky, László Nagy, Zoltán Szekanecz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number94
JournalArthritis Research and Therapy
Volume21
Issue number1
DOIs
StatePublished - Apr 15 2019
Externally publishedYes

Keywords

  • Atherosclerosis
  • Certolizumab pegol
  • Etanercept
  • Gene expression
  • Genetic signature
  • Prediction
  • Response
  • Rheumatoid arthritis
  • Vascular pathology

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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