Patients with ankylosing spondylitis and low disease activity because of anti-TNF-alpha therapy have higher TRAIL levels than controls: a potential compensatory effect.

Fernanda Genre,Ricardo Blanco,José A Miranda-Filloy,Carlos González-Juanatey,Begoña Ubilla,Trinitario Pina,Javier Rueda-Gotor,Miguel A González-Gay,Inés Gómez-Acebo,Beatriz Carnero-López,Rodrigo Ochoa,Natalia Palmou-Fontana,Javier Llorca,Raquel López-Mejías

doi:10.1155/2014/798060

Abstract

Objective. TRAIL is a potential biomarker of cardiovascular (CV) disease. Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with metabolic syndrome (MeS) and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.

Highlights

Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with high incidence of cardiovascular (CV) mortality due to accelerated atherosclerosis [1]
Since TNF-α blockade may account for biological changes that may slow the progression of atherosclerosis in AS patients [13], the analysis of the potential influence of treatment with anti-TNF-α drugs on disease activity, systemic inflammation, metabolic syndrome (MeS), and new potential CV risk biomarkers might help us to understand the effect of these biologic agents on the mechanism associated with atherosclerosis in AS patients
Apart from being involved in the apoptotic process, TNF-related apoptosis-inducing ligand (TRAIL) exerts anti-inflammatory and antiatherosclerotic functions [16,17,18]. Taking all these considerations into account, in the present study, we aimed to study if TRAIL serum levels were altered in AS patients undergoing infliximab therapy when compared to controls

Summary

Introduction

Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with high incidence of cardiovascular (CV) mortality due to accelerated atherosclerosis [1]. AS patients often display metabolic syndrome (MeS) features, which include obesity, dyslipidemia, hypertension, alterations in glucose metabolism, including insulin resistance (IR), and a dysregulation of adipokines [2]. A single infusion of anti-TNF-α monoclonal antibody infliximab improved insulin sensitivity in nondiabetic AS patients [4]. Since TNF-α blockade may account for biological changes that may slow the progression of atherosclerosis in AS patients [13], the analysis of the potential influence of treatment with anti-TNF-α drugs on disease activity, systemic inflammation, MeS, and new potential CV risk biomarkers might help us to understand the effect of these biologic agents on the mechanism associated with atherosclerosis in AS patients

Methods

Results

Conclusion