Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study

Abstract

Rationale Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. Objectives To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Methods Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. Measurements and Main Results 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. Conclusions We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

sRAGE as severe acute bronchiolitis biomarker, prospective observational study

“…In spite of the AGE‐RAGE axis playing a direct role in immune cell recruitment, adhesion, and differentiation during the acute inflammatory response, 19 this study found no relationship between peripheral blood WCC and sRAGE levels, in accordance with the literature 27,33 …”

“…Both Mauri et al 34 and Wiegers et al 35 described the changes in biomarkers levels overtime after an inflammatory insult: sRAGE increased earlier than CRP (or PCT) and then decreased quickly and consistently. This could be the reason why sRAGE levels show no correlation with CRP or PCT when determined on the first 24 hours of admission 15,27 and, on the other hand, show a positive correlation when measured after 72 hours or at different time points, like in our study 36 …”

“…Moreover, mRAGE can lead to opposite effects depending on it's ligands properties and the tissue affected 11 . Some lung diseases appear to have elevated mRAGE and RAGE ligands levels (asthma, cystic fibrosis, acute lung injury [ALI], acute respiratory distress syndrome [ARDS], bronchopulmonary dysplasia [BPD] or pneumonia) while they are reduced in others (interstitial lung disease and certain lung cancers) 13,14,20‐29 . Simultaneously, sRAGE levels decrease in most of the respiratory illnesses with increased mRAGE, except for ALI/ARDS 20,23 …”

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

“…In addition to the normal role of RAGE associated with innate immunity, it can also orchestrate cellular proliferation and differentiation [ 27 ]. Thus, increases in the RAGE ligands have also been implicated in a range of disease states, such as Alzheimer’s Disease, diabetes, and during tumor growth [ 19 , 28 , 29 ].…”

The Relationship between the Soluble Receptor for Advanced Glycation End Products and Oxidative Stress in Patients with Palmoplantar Warts

“…There is no clear evidence of the etiopathogenic mechanisms of HPV infection. Multiple factors contributing to its pathogenesis have been suggested, such as the lack of efficient protective cell mechanisms against the virus and the accumulation of toxic compounds which induce oxidative stress and inflammation [14,15,16,17,18,19]. Oxidative stress and inflammation are two interconnected processes which produce multiple effects on cell function [20].…”