Assessment of EN-RAGE, sRAGE and EN-RAGE/sRAGE as potential biomarkers in patients with autoimmune hepatitis

Abstract

Background Autoimmune hepatitis (AIH) is a liver disease characterized by the autoimmune-induced injury of hepatocytes which can lead to cirrhosis and hepatic failure. The diagnosis and disease management of AIH patients remain challenging due to the diversity of clinical phenotypes and the presence of confounders such as alcohol and viruses. Recently, EN-RAGE and sRAGEs have been implicated in inflammatory-immune response. Nonetheless, their natural behaviour and relationship to disease activity as well as clinical predictive values in AIH development or therapy-induced remission have not been reported. Methods Sixty-seven AIH patients and thirty gender- and age-matched healthy controls (HC) were enrolled. The serum concentrations of EN-RAGE, sRAGE and their ratio (EN-RAGE/sRAGE) in these subjects were measured by ELISA. Besides, the correlations of three parameters with clinical features and therapeutic response were analyzed, respectively. Furthermore, their potential predictive values for monitoring the AIH progression and therapeutic response were also evaluated. Results Higher serum EN-RAGE, lower sRAGE and higher EN-RAGE/sRAGE value were observed in AIH patients. EN-RAGE and sRAGE as well as EN-RAGE/sRAGE were correlated with liver necroinflammation parameters, cirrhosis occurrence and therapeutic response. In addition, we identified that EN-RAGE/sRAGE, EN-RAGE and sRAGE had valuable predicting power for AIH patients, AIH patients with normal ALT and cirrhosis incidence, respectively. More importantly, EN-RAGE/sRAGE also exerted predicting power for the remission in AIH patients. Conclusions AIH patients rendered distinct patterns of serum EN-RAGE, sRAGE or EN-RAGE/sRAGE compared to healthy controls. Moreover, these three parameters exhibited potentials as novel biomarkers for AIH diagnosis and prognosis evaluation.

Serum Levels of Soluble Receptor for Advanced Glycation End Products Are Reduced in Euthyroid Children with Newly Diagnosed Hashimoto’s Thyroiditis: A Pilot Study

“…Advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs), products of nonenzymatic transformation of macromolecules, have been proposed as potential markers of oxidative stress in autoimmune diseases, including HT [21-26]. In particular, AGEs can activate an intrinsic signaling pathway inside the cells by interacting with their receptor (RAGE) on cell membrane, leading to altered cell function and oxidative damage [27, 28].…”

Reduced Circulating Soluble Receptor for Advanced Glycation End-products in Chronic Hepatitis B Are Associated with Hepatic Necroinflammation

“…sRAGE, a circulating soluble isoform of RAGE, has recently gained interest due to its potential to ameliorate in ammation by competing with cell surface RAGE for ligand binding under pathological conditions. sRAGE can be detected in human serum and has been implicated in liver diseases, including nonalcoholic fatty liver disease (NAFLD) [19], autoimmune hepatitis [20] and HCC [21].…”

RAGE against the Machine: Can Increasing Our Understanding of RAGE Help Us to Battle SARS-CoV-2 Infection in Pregnancy?

“…RAGE exerts its physiological and pathological effects through its ability to bind with a multitude of ligands. These include several of the DAMPs, such as high-mobility group box 1 (HMGB1), certain S100 proteins, Amyloid β, DNA and RNA, and AGE [ 15 ]. However, the specific signaling responses that are precipitated by ligand binding not only depend on the specific ligand/RAGE pairing [ 26 ], but also on the cell type that it is expressed on.…”

“…However, this is obviously compounded in this population if they have any of the comorbidities that increase the risk for severe SARS-CoV-2 [ 150 , 151 ]. Furthermore, social inequities, such as access to healthcare, are an issue for many pregnant women in Hawai’i, as 1 in 17 child-bearing-aged women are uninsured [ 15 , 42 ]. Thus, there is a need to collect more comprehensive data to determine the key factors that influence the health of the pregnant population in Hawai’i, and to therefore improve the severe disparities that are faced by our Indigenous communities, and especially while we are battling the ongoing pandemic.…”

“…One receptor that has been shown to be key for the detection of various ligands, and that is known to be activated at the end of pregnancy, is the receptor of advanced glycation end products (RAGE) [ 14 ]. It interacts with danger-associated molecular patterns (DAMPs), which are generated by cellular stress [ 15 ], and advanced glycation end products (AGE), which are produced by the combination of fat or protein with sugars in the bloodstream [ 16 , 17 ]. The activation of RAGE results in the activation of the proinflammatory transcription factors Nuclear Factor Kappa B (NF-κB) and Activator Protein 1 (AP1), and oxidative-stress-response genes [ 18 , 19 , 20 ].…”