Exploring Immune-Related Biomarkers in Human Itch

Abstract: Itch is a debilitating symptom that affects ∼40% of the population and significantly impacts patients' quality of life. The management of chronic itch remains a significant challenge due to the limited availability of reliable biomarkers for assessing its severity. This review aims to investigate the key neuroimmune-related biomarkers involved in the pathophysiology of itch and itch-dependent diseases. A thorough literature review was conducted using PubMed and Google Scholar, employing search terms like "Biomarkers" OR "Blood markers" OR "Immune-related" AND "Itch" OR "Pruritus." Recent evidence has highlighted the central role of neuro-immune-epithelial crosstalk in itch pathogenesis, with pruritogens stimulating the release of interleukin-33 (IL-33), thymic stromal lymphopoietin, and periostin, which promote Th2 inflammation and intensify itch sensation. Elevated levels of cytokines such as IL-4, IL-13, and IL-31 have been associated with various inflammatory skin conditions, though their correlation with itch severity remains inconsistent. Chemokines like thymus and activation-regulated chemokine, as well as CC motif chemokine ligand, have demonstrated promise as biomarkers for Th2-mediated conditions, showing correlations with disease severity and itch intensity. Additional markers, such as brain natriuretic peptide and its metabolite NT-proBNP, have been correlated with itch intensity in chronic pruritic conditions. However, neuropeptides like substance P have shown limited utility in evaluating itch severity. Understanding the mechanisms underlying itch through immune-related biomarkers could lead to more effective treatments and enhance patient outcomes while providing insights into immune dysregulation in pruritic disorders.