Serum thiols as a biomarker of disease activity in lupus nephritis.

Pritesh Lalwani,Antonio Luiz Boechat,Luiz Fernando Souza Passos,Emerson Silva Lima,Giselle Katiane Bonfim Bacelar De Souza,Domingos Savio Nunes De Lima,Jose Crispin

doi:10.1371/journal.pone.0119947

Abstract

Lupus Nephritis (LN) develops in more than half of the Systemic Lupus Erythematous (SLE) patients. However, lack of reliable, specific biomarkers for LN hampers clinical management of patients and impedes development of new therapeutics. The goal of this study was to investigate whether oxidative stress biomarkers in patients with SLE is predictive of renal pathology. Serum biochemical and oxidative stress markers were measured in patients with inactive lupus, active lupus with and without nephritis and compared to healthy control group. To assess the predictive performance of biomarkers, Receiver Operating Characteristic (ROC) curves were constructed and cut-offs were used to identify SLE patients with nephritis. We observed an increased oxidative stress response in all SLE patients compared to healthy controls. Among the several biomarkers tested, serum thiols had a significant inverse association with SLE Disease Activity Index (SLEDAI). Interestingly, thiols were able too aptly differentiate between SLE patients with and without renal pathology, and serum thiol levels were not affected by immunosuppressive drug therapy. The decreased thiols in SLE correlated significantly with serum creatinine and serum C3 levels. Further retrospective evaluation using serum creatinine or C3 levels in combination with thiol’s cutoff values from ROC analysis, we could positively predict chronicity of renal pathology in SLE patients. In summary, serum thiols emerge as an inexpensive and reliable indicator of LN, which may not only help in early identification of renal pathology but also aid in the therapeutic management of the disease, in developing countries with resource poor settings.

Highlights

Systemic lupus erythematous (SLE) is a multisystem autoimmune inflammatory disease for which etiology and pathogenesis are incompletely understood [1]
Lupus Nephritis (LN) patients (n = 31) were identified by clinical and laboratorial diagnosis, 15 (48%) of the biopsied patients had a mean chronicity index ranged from 2.54 to 4.81 and the mean activity index ranged from 8.65 to 11.89; the patients included in the study had class type II (n = 1), type III (n = 9), type IV (n = 20), type V (n = 1) grade of disease according to the International Society of Nephrology (ISN) criteria for SLE nephritis classification
A greater use of mycophenolate mofetil/sodium and cyclophosphamide was observed in treating Active Lupus (AL) and NL group compared to Inactive lupus (IL) patients

Summary

Introduction

Systemic lupus erythematous (SLE) is a multisystem autoimmune inflammatory disease for which etiology and pathogenesis are incompletely understood [1]. Thiols Marker of Disease Activity in Lupus Nephritis hormonal, and environmental factors [2]. The highest incidence of SLE is reported from tropical Brazil, and appears to be increasing as the disease is recognized more readily and patient survival rate increases [6]. Evaluation for lupus nephritis (LN) includes urine sediment analysis, urinary protein and creatinine excretion, determination of serum creatinine and assessment of serological markers, such as anti-dsDNA antibody titers and, C3 and C4 complement levels [9,10]. The use of aggressive immunosuppression has improved patient survival over the past several decades, managing relapses or flares requires constant follow-up and surveillance, which often entails changing treatments and remains challenging in LN [11]

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