Soluble Vascular Biomarkers in Rheumatoid Arthritis and Ankylosing Spondylitis: Effects of 1-year Antitumor Necrosis Factor-α Therapy

Anita Pusztai; Attila Hamar; Ágnes Horváth; Katalin Gulyás; Edit Végh; Nóra Bodnár; György Kerekes; Monika Czókolyová; Szilvia Szamosi; Levente Bodoki; Katalin Hodosi; Andrea Domján; Gábor Nagy; Ibolya Szöllősi; Luis R Lopez; Eiji Matsuura; Zoltán Prohászka; Sándor Szántó; Zoltán Nagy; Yehuda Shoenfeld; Zoltán Szekanecz; Gabriella Szűcs

doi:10.3899/jrheum.200916

Soluble Vascular Biomarkers in Rheumatoid Arthritis and Ankylosing Spondylitis: Effects of 1-year Antitumor Necrosis Factor-α Therapy

J Rheumatol. 2021 Jun;48(6):821-828. doi: 10.3899/jrheum.200916. Epub 2020 Dec 15.

Authors

Anita Pusztai¹, Attila Hamar¹, Ágnes Horváth¹, Katalin Gulyás¹, Edit Végh¹, Nóra Bodnár¹, György Kerekes², Monika Czókolyová¹, Szilvia Szamosi¹, Levente Bodoki¹, Katalin Hodosi¹, Andrea Domján¹, Gábor Nagy³, Ibolya Szöllősi³, Luis R Lopez⁴, Eiji Matsuura⁵, Zoltán Prohászka⁶, Sándor Szántó⁷, Zoltán Nagy¹, Yehuda Shoenfeld⁸, Zoltán Szekanecz⁹, Gabriella Szűcs¹

Affiliations

¹ A. Pusztai, A. Hamar, MD, Á. Horváth, MD, K. Gulyás, MD, E. Végh, MD, N. Bodnár, MD, PhD, M. Czókolyová, S. Szamosi, MD, PhD, L. Bodoki, MD, PhD, K. Hodosi, A. Domján, Z. Nagy, MD, PhD, Z. Szekanecz, MD, PhD, G. Szűcs, MD, PhD, Division of Rheumatology, Department of Medicine, University of Debrecen, Debrecen, Hungary.
² G. Kerekes, MD, PhD, Intensive Care Unit, Department of Medicine, University of Debrecen, Debrecen, Hungary.
³ G. Nagy, MD, PhD, I. Szöllősi, Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary.
⁴ L.R. Lopez, MD, PhD, Corgenix Inc., Broomfield, Colorado, USA.
⁵ E. Matsuura, MD, PhD, Okayama University Graduate School of Medicine, Okayama, Japan.
⁶ Z. Prohászka, MD, PhD, Third Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
⁷ S. Szántó, MD, PhD, Division of Rheumatology, Department of Medicine, and Department of Sports Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁸ Y. Shoenfeld, MD, PhD, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
⁹ A. Pusztai, A. Hamar, MD, Á. Horváth, MD, K. Gulyás, MD, E. Végh, MD, N. Bodnár, MD, PhD, M. Czókolyová, S. Szamosi, MD, PhD, L. Bodoki, MD, PhD, K. Hodosi, A. Domján, Z. Nagy, MD, PhD, Z. Szekanecz, MD, PhD, G. Szűcs, MD, PhD, Division of Rheumatology, Department of Medicine, University of Debrecen, Debrecen, Hungary; szekanecz.zoltan@med.unideb.hu.

PMID: 33323530
DOI: 10.3899/jrheum.200916

Abstract

Objective: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with cardiovascular disease. The treatment of arthritis by tumor necrosis factor-α (TNF-α) inhibitors may decrease the serum concentrations of vascular biomarkers. We determined circulating levels of oxidized low-density lipoprotein (oxLDL)/β₂ glycoprotein I (β₂-GPI) complexes, antibodies to 60 kDa heat shock protein (anti-Hsp60), soluble urokinase plasminogen activator receptor (suPAR), and B-type natriuretic peptide (BNP) fragment in sera of RA and AS patients undergoing anti-TNF treatment.

Methods: Fifty-three patients with RA/AS were treated with etanercept or certolizumab pegol for 1 year. Circulating oxLDL/β₂-GPI complex (AtherOx), anti-Hsp60 IgG, and BNP8-29 fragment levels were assessed by ELISA. suPAR levels were determined by suPARnostic Quick Triage test. Flow-mediated vasodilation (FMD), carotid intima-media thickness (CIMT), and arterial pulse wave velocity (PWV) were determined by ultrasound.

Results: One-year anti-TNF treatment significantly decreased oxLDL/β₂-GPI levels, as well as suPAR levels in patients with critically high suPAR levels at baseline. In RA, BNP levels were higher in seropositive vs seronegative patients. Serum levels of these vascular biomarkers variably correlated with lipids, anticitrullinated protein antibodies, rheumatoid factor, and C-reactive protein. CIMT positively correlated with BNP, and PWV with suPAR and anti-Hsp60, whereas FMD inversely associated with anti-Hsp60. In repeated measures ANOVA analysis, disease activity supported the effects of anti-TNF treatment on 12-month changes in oxLDL/β₂-GPI. CIMT supported the effects of therapy on changes in anti-Hsp60 and suPAR.

Conclusion: These biomarkers may be involved in the pathogenesis of atherosclerosis underlying RA/AS. TNF inhibition variably affects the serum levels of oxLDL/β₂-GPI, suPAR, and BNP.

Keywords: angiogenesis; anti-TNF therapy; atherosclerosis; biomarkers; rheumatoid arthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid* / drug therapy
Biomarkers
Carotid Intima-Media Thickness
Humans
Necrosis
Pulse Wave Analysis
Spondylitis, Ankylosing* / drug therapy
Tumor Necrosis Factor Inhibitors / therapeutic use*

Substances

Biomarkers
Tumor Necrosis Factor Inhibitors