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

Abstract

Objective Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with cardiovascular (CV) disease. The treatment of arthritis by tumour necrosis factor α (TNF- α) inhibitors may decrease the serum concentrations of vascular biomarkers. We determined circulating levels of oxidized LDL (oxLDL)/β2 glycoprotein I (β2GPI) complexes, antibodies to 60 kDa heat shock protein (anti-Hsp60), soluble urokinase plasminogen activator receptor (suPAR) and Brain type natriuretic peptide (BNP) fragment in sera of RA and AS patients undergoing anti-TNF treatment. Methods Fifty-three RA/AS patients were treated with etanercept (ETN) or certolizumab pegol (CZP) for one year. Circulating oxLDL/β2GPI 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 (IMT) and arterial pulse-wave velocity (PWV) were determined by ultrasound. Results One-year anti-TNF treatment significantly decreased oxLDL/β2GPI 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, ACPA, RF and CRP. IMT positively correlated with BNP, PWV with suPAR and anti-Hsp60, while FMD inversely associated with anti-Hsp60. In RM-ANOVA analysis, disease activity supported the effects of anti-TNF treatment on 12-month changes in oxLDL/β2GPI. IMT supported the effects of therapy on changes of anti-Hsp60 and suPAR. Conclusion These biomarkers may be involved in the pathogenesis of atherosclerosis underlying RA/AS. TNF inhibition variably affect the serum levels of oxLDL/β2GPI, suPAR and BNP.

Angiotensin Converting Enzyme Activity in Anti-TNF-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients

“…Separate vascular imaging, as well as disease activity, inflammatory and vascular biomarker data obtained in the very same cohort have been published (19,56,57). Here we used those data to associate them with the ACE and ACE2 measurements.…”

“…Fifty one patients with inflammatory arthritis (35 RA and 16 axial radiographic AS) selected for the initiation of anti-TNF therapy but unselected for CV disease (any previous CV events) were enrolled in the study as described before (19,56,57). These patients were consecutively selected in one tertiary rheumatology center (University of Debrecen).…”

“…Yet, very little information has become available on the effects of anti-TNF therapy on ACE and ACE2 production and on their correlation with disease activity, markers of inflammation, autoantibodies and vascular pathophysiology. We have recently set up a mixed cohort of RA and AS patients and reported multiple effects of anti-TNF treatment over one year on vascular pathophysiology (19) and various vascular biomarkers (56,57). We have published data on vascular pathophysiology and bone in the very same cohort before (19,56,(58)(59)(60).…”

Natural Autoantibodies in Biologic-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients: Associations with Vascular Pathophysiology

“…Autoantibodies to heat shock proteins (Hsp), such as anti-human Hsp60 and anti-Mycobacterial Hsp65, have also been characterized as nAAbs [ 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Anti-Hsp autoantibodies have also been implicated in inflammation, autoimmunity, and atherosclerosis [ 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Antibodies to Hsps trigger early atherosclerosis in various animal models [ 10 , 11 ].…”

“…Moreover, anti-Hsp60 antibodies have been correlated with ASCVD in humans [ 6 , 14 , 15 ]. Among inflammatory rheumatic diseases, nAAbs to Mycobacterial Hsp65 and human Hsp60 have been detected in RA, AS, SLE, and SSc [ 6 , 9 , 12 , 14 , 15 , 16 , 17 , 18 ]. Moreover, anti-Hsp autoantibodies have been implicated in early atherosclerosis associated with various autoimmune-rheumatic diseases [ 14 , 15 ].…”