Serum Thiols as a Biomarker of Disease Activity in Lupus Nephritis

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.

Oxidative Stress in Kidney Diseases: The Cause or the Consequence?

“…While numerous works have evaluated the oxidant-related biomarkers in CKD, there is a scarcity of studies examining the natural body antioxidants in this disease. One of such studies has included systemic lupus erythematous (SLE) patients with nephritis (Lalwani et al 2015 ). The results of this study have shown that decreased serum thiols levels are correlated to creatinine and serum C3 levels.…”

“…Interestingly, it has been suggested that thiol levels may be used to differentiate between SLE patients with and without renal pathology (serum thiol levels are not affected by immunosuppressive drug therapy). It is possible that combination of thiols and creatinine or C3 serum levels may be used as a future predictive biomarker of chronicity of renal pathology in SLE patients (Lalwani et al 2015 ).…”

Increased adhesion molecule levels in systemic lupus erythematosus: relationships with severity of illness, autoimmunity, metabolic syndrome and cortisol levels

“…2 Elevated adhesion molecule levels have also been associated with disease activity 3 and its characteristic phenotypes, 4 including cutaneous manifestations, 5 neurological disorders 6 and lupus nephritis. 7 Adhesion molecules have been studied as potential biomarkers for SLE with respect to its activity and clinical manifestations. 8 Changes in cell adhesive interactions in SLE are frequently accompanied by vascular changes and cellular infiltration of tissues.…”

The association of thiol/disulphide homeostasis with 6-month mortality in patients with acute st-elevation myocardial infarction

“…The main findings of our study can be summarized as follows: Aside from the acute coronary syndrome itself, some other clinical conditions as diabetes mellitus [18], hypertension [19], stable coronary arterial disease [20], chronic kidney disease [21], autoimmune diseases [22][23][24][25] [29], however, their study failed to yield an association of inhospital mortality with neither native and total thiol levels nor native thiol/disulphide ratio. Aside from the afore-mentioned studies, our study merely investigated all-cause mortality during 6-month follow-op of patients with STMI, and we did not find any correlation between the mortality and admission parameters related to the thiol/disulphide homeostasis.…”