Role of Cathepsin H, Cathepsin S, Chitinase-3–like protein 1, and other biomarkers in Multiple Sclerosis patients

Abstract

The study aims to assess the potential of cathepsin S, cathepsin H, and other biomarkers as diagnostic and prognostic indicators in patients with multiple sclerosis. A total of 280 participants aged 25–45 years were collected from Baghdad Medical City/Baghdad/Iraq, between May 2025 and January 2026. They were divided into three groups according to the McDonald criteria: relapsing-remitting (N=70), secondary progressive (N=70), and primary progressive (N=70) MS, based on neurological assessment. Serum and paired CSF samples were analyzed using ultra-sensitive immunoassays for all biomarkers (NfL, GFAP, chitinase-3–like protein 1 (CHI3L1), CXCL13, MMP-9, Cathepsin S, Cathepsin H, NSPs, AAP-1, and CBC) in discriminating relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). CSF biomarkers consistently outperformed serum markers across all disease subtypes. In RRMS, CSF NfL achieved an AUC compared with serum NfL. Similarly, CSF GFAP yielded an AUC versus serum. CHI3L1, CXCL13, and MMP-9 demonstrated parallel trends, with CSF AUCs ranging versus serum. The highest discriminative accuracy was observed for CSF NfL in PPMS. Composite ROC visualization confirmed the superior performance of CSF biomarkers across all subtypes. CSF-derived biomarkers exhibit higher diagnostic accuracy than serum counterparts, reflecting direct proximity to neuroinflammatory and neurodegenerative processes.