Abstract: Provided herein are methods and immune biomarkers that identify progression and treatment options for multiple sclerosis (MS). Also provided are materials and methods for the prognosis, staging, and monitoring of MS in a sample and include methods of determining a subject as being at risk of developing MS. The methods include detecting at least one biomarker, such as CXCL13, CXCL10, CD27, NEFL, CCL4, and/or CCL3 in cerebrospinal fluid (CSF) in the subject; and administering a pharmaceutically effective amount of a treatment (e.g., tolebrutinib and potentially one or more additional therapies, such as an anti-CD20 therapy) to the subject.