Serum GlycA Level is Elevated in Active Systemic Lupus Erythematosus and Correlates to Disease Activity and Lupus Nephritis Severity.

Noémie Jourde-Chiche,Bernard Lauwerys,Tim Dierckx,Laurent Daniel,Johan Van Weyenbergh,Laurent Chiche

doi:10.3390/jcm9040970

Abstract

Objective: Reliable non-invasive biomarkers are needed to assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). Glycoprotein acetylation (GlycA), a novel biomarker for chronic inflammation, has been reported to be increased in several inflammatory diseases. We investigated the relevance of serum GlycA in SLE patients exhibiting various levels of activity and severity, especially with regards to renal involvement. Methods: Serum GlycA was measured by nuclear magnetic resonance spectroscopy in samples from well characterized SLE patients and from both healthy controls and patients with other kidney diseases (KD). Disease activity was evaluated using the Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K). Renal severity was assessed by kidney biopsy. Results: Serum GlycA was elevated in active (n = 105) compared to quiescent SLE patients (n = 39, p < 10−6), healthy controls (n = 20, p = 0.009) and KD controls (n = 21, p = 0.04), despite a more severely altered renal function in the latter. GlycA level was correlated to disease activity (SLEDAI-2K, ρ = 0.37, p < 10−4), C-reactive protein, neutrophil count, triglyceride levels, proteinuria and inversely to serum albumin. In patients with biopsy-proven lupus nephritis (LN), GlycA levels were higher in proliferative (n = 26) than non-proliferative LN (n = 10) in univariate analysis (p = 0.04), and was shown to predict proliferative LN independently of renal parameters, immunological activity, neutrophil count and daily corticosteroid dosage by multivariate analysis (p < 5 × 10−3 for all models). In LN patients with repeated longitudinal GlycA measurement (n = 11), GlycA varied over time and seemed to peak at the time of the flare. Conclusions: GlycA, as a summary measure for different inflammatory processes, could be a valuable biomarker of disease activity in patients with SLE, and a non-invasive biomarker of pathological severity in the context of LN.

Highlights

Reliable and non-invasive biomarkers are still needed in systemic lupus erythematosus (SLE) to assess disease activity, severity of organ involvement, and long-term prognosis [1]
We recently showed that Glycoprotein acetylation (GlycA) could be a marker of disease activity in inflammatory bowel disease in patients without C-reactive protein (CRP) elevation [18]
Large scale gene correlation network analysis has shown that GlycA can be associated to neutrophil gene expression [16], which has been shown to be associated with Lupus nephritis (LN) occurrence and severity in SLE patients [19,20]

Summary

Introduction

Reliable and non-invasive biomarkers are still needed in systemic lupus erythematosus (SLE) to assess disease activity, severity of organ involvement, and long-term prognosis [1]. The GlycA signal can be interpreted as a biomarker of systemic inflammation [12], summarizing the activity of multiple inflammatory pathways [13]. GlycA has been shown to be associated with the risk of cardiovascular events, cardiovascular mortality and all-cause mortality in the general population, independently of CRP [14,15,16]. We recently showed that GlycA could be a marker of disease activity in inflammatory bowel disease in patients without CRP elevation [18]. Large scale gene correlation network analysis has shown that GlycA can be associated to neutrophil gene expression [16], which has been shown to be associated with LN occurrence and severity in SLE patients [19,20]

Methods

Results

Conclusion