BTK and YKL-40 Levels and Their Association with Acute AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

Abstract

This study investigated the potential correlation between BTK/YKL-40 levels and the severity of AQP4-IgG + NMOSD, aiming to identify biomarkers for disease monitoring and treatment assessment. Plasma YKL-40 expression was measured in 135 AQP4-IgG + NMOSD patients using ELISA. Patients were categorized into pre- and post-IVMP treatment acute phases, as well as during remission, with a healthy control group included. BTK and NF-κB mRNA levels in PBMCs were detected via q-PCR, and BTK/P-BTK protein expression was assessed using Western blotting. Disability was evaluated using the EDSS score, and clinical characteristics were evaluated alongside laboratory tests. Acute-phase NMOSD patients receiving pre-IVMP therapy presented significantly elevated plasma YKL-40 concentrations compared with those of post-treatment patients, patients in remission, and healthy controls. Additionally, these patients presented significantly higher levels of PBMC BTK mRNA, NF-κB mRNA, BTK, and P-BTK protein expression than remission patients and healthy controls. Plasma YKL-40 levels and PBMC BTK/P-BTK protein levels were positively correlated with EDSS scores. The plasma YKL-40 concentration significantly contributes to disease severity and serves as an independent risk factor for acute NMOSD. Elevated BTK, P-BTK, NF-κB, and YKL-40 levels were observed in acute-phase AQP4-IgG + NMOSD patients. These biomarkers are related to disease activity and may predict treatment efficacy. There is a connection among YKL-40, BTK, and P-BTK levels and disease severity, suggesting their potential involvement in the pathogenic mechanism of AQP4-IgG + NMOSD.