The methods disclosed herein include diagnosing a patient with MS, selecting a patient for further testing for MS, should the patient show elevated level of human IgG relative to an appropriate control. The methods also include differentiating subtypes of MS. The methods also include evaluating the efficacy of an MS drug or course of drug treatments, and/or treating MS. The methods include determining whether patients have elevated levels of IgG3-IgG1 immune complexes (which can include glycosylated IgG antibodies) in both blood and CSF. Methods also include diagnosing patients with primary-progressive MS (PPMS) and secondary- progressive MS (SPMS) where patients have higher levels of IgG3-IgG1 complexes in both CSF and blood, and reduced levels of albumin compared to patients with relapsing-remitting MS (RRMS). The methods optionally include treating the sample to dissociate immune and/or protein complexes, contacting the sample with a reagent that binds specifically to a human IgG or other protein, comparing the results to an appropriate control, and determining whether the patient has an altered level of IgG or other protein consistent with MS.
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