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, G. Kerekes, Z. Szabó, Zoltán Nagy, G. Szűcs, S. Szántó, Gábor Zahuczky, L. Nagy, Z. Szekanecz

Research output: Article

2 Citations (Scopus)

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
Article number94
JournalArthritis Research and Therapy
Volume21
Issue number1
DOIs
Publication statusPublished - ápr. 15 2019

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Blood Vessels
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Gene Expression
Pulse Wave Analysis
Vasodilation
Biological Products
Therapeutics
Transport Vesicles
Carotid Intima-Media Thickness
Gene Expression Profiling
Genes
Down-Regulation
Glucose
Mortality

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Gene expression analysis of vascular pathophysiology related to anti-TNF treatment in rheumatoid arthritis. / Póliska, Szilárd; Besenyei, Timea; Végh, Edit; Hamar, Attila; Pusztai, Anita; Váncsa, Andrea; Bodnár, Nóra; Szamosi, Szilvia; Csumita, Mária; Kerekes, G.; Szabó, Z.; Nagy, Zoltán; Szűcs, G.; Szántó, S.; Zahuczky, Gábor; Nagy, L.; Szekanecz, Z.

In: Arthritis Research and Therapy, Vol. 21, No. 1, 94, 15.04.2019.

Research output: Article

Póliska, Szilárd ; Besenyei, Timea ; Végh, Edit ; Hamar, Attila ; Pusztai, Anita ; Váncsa, Andrea ; Bodnár, Nóra ; Szamosi, Szilvia ; Csumita, Mária ; Kerekes, G. ; Szabó, Z. ; Nagy, Zoltán ; Szűcs, G. ; Szántó, S. ; Zahuczky, Gábor ; Nagy, L. ; Szekanecz, Z. / Gene expression analysis of vascular pathophysiology related to anti-TNF treatment in rheumatoid arthritis. In: Arthritis Research and Therapy. 2019 ; Vol. 21, No. 1.
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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-na{\"i}ve 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.",
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AU - Póliska, Szilárd

AU - Besenyei, Timea

AU - Végh, Edit

AU - Hamar, Attila

AU - Pusztai, Anita

AU - Váncsa, Andrea

AU - Bodnár, Nóra

AU - Szamosi, Szilvia

AU - Csumita, Mária

AU - Kerekes, G.

AU - Szabó, Z.

AU - Nagy, Zoltán

AU - Szűcs, G.

AU - Szántó, S.

AU - Zahuczky, Gábor

AU - Nagy, L.

AU - Szekanecz, Z.

PY - 2019/4/15

Y1 - 2019/4/15

N2 - 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.

AB - 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.

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KW - Certolizumab pegol

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KW - Gene expression

KW - Genetic signature

KW - Prediction

KW - Response

KW - Rheumatoid arthritis

KW - Vascular pathology

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