Erythrocyte glutathione transferase: a non-antibody biomarker for systemic sclerosis, which correlates with severity and activity of the disease

Abstract

Erythrocyte glutathione transferase (e-GST) is a detoxifying enzyme hyper-expressed in nephropathic patients and used recently as a biomarker for blood toxicity. Systemic sclerosis (SSc) is characterized by endothelial dysfunction and fibrosis of the skin and internal organs. Renal involvement is frequent in SSc patients. Here we show that e-GST is hyper-expressed in SSc patients (n=102) and correlates (R2=0.49, P<0.0001) with the Medsger DSS and DAI Valentini indices that quantify the severity and activity of this disease. Interestingly, e-GST does not correlate with the impairment of kidney or other specific organs taken separately. e-GST hyper-expression seems to be linked to the presence of a factor (i.e., toxin) that triggers the autoimmune disease, and not to the damage of specific organs or to oxidative stress. e-GST may be proposed as an innovative non-antibody biomarker for SSc useful to check the progress of this disease and the efficiency of new therapeutic strategies.

Glutathione Transferase P1-1 an Enzyme Useful in Biomedicine and as Biomarker in Clinical Practice and in Environmental Pollution

“…Surprisingly, e-GST levels of SSc patients were not influenced by the presence of kidney damage or by other defects of specific organs taken separately. Therefore e-GST hyper-expression in this condition appears to be linked with the exposure to putative toxins that cause the disease, rather than being caused by the autoimmune disease per se, by the damage of specific organs, or by other consequences of the disease that may also include OS [84].…”

“…The rates of autoimmune disorders are increasing in industrialized countries and greater attention is direct to improve diagnostic procedures and therapeutic interventions [85]. Only one study is based on the enzymatic level of e-GST in scleroderma [84]. The other studies reported in the literature focused on GSTP1 polymorphisms (see Section 3.6 and Table 1) in pathologies like systemic lupus erythematosus [86], or are meta-analysis suggesting that the GSTP1 polymorphisms are not associated with the risk of rheumatoid arthritis [87].…”

Erythrocyte glutathione transferase in kidney transplantation: a probe for kidney detoxification efficiency

“…Moreover, e-GST was found to be overexpressed in chronic kidney disease (CKD) patients under conservative therapy 17 , 20 and in type-2 diabetes mellitus patients (T2DM) with CKD 21 , 22 . Finally, environmental 23 and endogenous factors like autoimmune disease 24 also affected e-GST levels in healthy subjects and in non-uremic patients. In this study, we use e-GST like a probe able to assess functionality of transplant kidneys coming from living and cadavers donors in their specific action to scavenge endo and exogenous toxins.…”

Band 3 Protein Function and Oxidative Stress in Erythrocytes from Systemic Sclerosis Patients with Interstitial Lung Disease

“…Though its pathophysiology is still unclear, a link between reactive oxygen species (ROS) and SSc development has been ascertained [6]. In particular, high ROS levels in patients with diffuse cutaneous SSc (dcSSc) have been associated with increased levels of oxidative stress markers, alteration of antioxidant mechanisms, reduced non-enzymatic antioxidants, such as ascorbic acid, αtocopherol, β-carotene and selenium and reduced antioxidant defense [7][8][9][10]. The link between oxidative stress and SSc has been further supported by a mouse model exhibiting a disease closely resembling human SSc when administered hypochlorous acid, as oxidative agent [11].…”