Glutathione-CRP Inflammatory Index: A Novel Biomarker Differentiating Acute Versus Chronic Inflammation Depth and Clinical Implications via Redox-Immune Pathway Integration

Background: Chronic inflammation drives pathologies such as prediabetes, type ۲ diabetes, colorectal cancer (CRC), severe community-acquired pneumonia (CAP), and liver cirrhosis, yet biomarkers like high-sensitivity C-reactive protein (hsCRP) or interleukin-۶ (IL-۶) may lack specificity for oxidative-inflammatory depth. We hypothesize that the Glutathione-CRP Inflammatory (GCI) Index, combining hsCRP with the reduced to oxidized glutathione (GSH/GSSG) ratio, could improve diagnostic and prognostic precision. Methods: Archival datasets from prediabetes (n=۶۳), type ۲ diabetes (n=۵۰), CRC (n=۸۰), CAP (n=۲۶۷), and liver cirrhosis (n=۷۵) were analyzed. GCI was calculated as (hsCRP/۱۰ mg/L) + (GSSG/(GSH+GSSG)), normalized to ۰–۱۰۰ using clinical ranges (hsCRP ۰–۱۰ mg/L, GSSG/(GSH+GSSG) ۰–۰.۱), and evaluated via logistic regression, receiver operating characteristic (ROC) analysis (hypothesizing ۰.۰۵–۰.۱۵ AUC improvement), LASSO regularization, and Cox proportional hazards models, adjusting for age, BMI, smoking, and medications. Results: GCI scores might differentiate inflammation types, with values potentially reaching ۸۲ in CRC, ۸۵ in CAP non-survivors, and ۸۰ in Child-Pugh B-C cirrhosis, suggesting associations with tumor progression, mortality, or hepatic decompensation.In diabetes, scores could decline from ۷۲ to ۵۸ post-GSH supplementation, indicating therapeutic response. GCI may outperform hsCRP (AUC ۰.۸۴۱ vs. ۰.۷۸۰ in CAP) and volatile IL-۶, driven by NF-κB-mediated hsCRP elevation and ROS-induced GSH depletion disrupting Nrf۲ antioxidant defenses. Conclusion: The GCI Index could enhance chronic disease assessment, pending prospective validation for integration into clinical panels alongside hsCRP or HbA۱c.

کلیدواژه ها:

GCI Index ، HSCRP ، GSH/GSSG ، NF-&kappa ، B/Nrf۲ Pathways ، chronic inflammation ، oxidative stress