Intrathecally produced CXCL13: A predictive biomarker in multiple sclerosis

Background Clinicians caring for patients with Multiple Sclerosis (MS) need improved biomarkers to aid them in disease management. Objective We assessed the predictive value of the candidate biomarker CXCL13 index in comparison to oligoclonal bands (OCBs) and CSF neurofilament light (NfL) concentration, examining the ability of each biomarker to predict future disease activity in clinically and radiologically isolated syndromes, relapsing-remitting MS, and progressive MS. Methods Matched serum and CSF samples were obtained from 67 non-inflammatory neurologic disease patients and 67 MS patients. CSF and serum CXCL13 and CSF NfL were analyzed by Luminex and ELISA, respectively. CXCL13 data were also analyzed as CSF/serum ratios and indices. Electronic medical records were accessed to determine diagnosis, CSF profiles, and disease activity after the lumbar puncture. Results Among CXCL13 measures, CXCL13 index was the best predictor of future disease activity in MS patients (AUC=0.82; CI=0.69-0.95; p=0.0002). CXCL13 index values were significantly elevated in activity-positive MS patients compared to activity-negative patients (p<0.0001). As a single predictor, CXCL13 index outperformed both OCBs and CSF NfL in sensitivity, specificity, and positive and negative predictive value, for future disease activity in MS patients. Moreover, combining CXCL13 index and CSF NfL status improved sensitivity and predictive values for disease activity in MS patients. Conclusions The CXCL13 index is an excellent candidate prognostic biomarker for disease activity in patients with MS.