To evaluate elevated immunoglobulin G (IgG) index as a diagnostic and prognostic biomarker for multiple sclerosis (MS).

Diagnosis for MS remains a clinical challenge. The predictive value of oligoclonal bands (OCB) and neurofilament levels are drawing more attention to cerebrospinal fluid measurement. However, those tests are not in wide use in developing countries. By contrast, IgG index, a routinely-performed examination indicative of intrathecal protein synthesis, may serve as an ideal substitute. Yet its diagnostic and prognostic value has not been fully addressed.

Patients with a demyelinating attack were prospectively recruited between 2012 and 2018 at the Second Affiliated Hospital of Zhejiang University. Only patients with available IgG index at baseline were included. Demographic and clinical data at onset, and disease activity in the first 2 years were retrospectively analyzed. Diagnostic performance of the modified criteria (using IgG index as an OCB substitute) and the 2017 McDonald criteria were further compared.

A total of 150 patients were included. Baseline IgG index was more frequently elevated in patients later diagnosed with RRMS (65% in RRMS vs. 12.5% in other disorders, P < 0.0001). For CIS patients (n=73) in the cohort, an elevated IgG index (>0.7) at baseline was predictive of a shorter time to the second relapse (Log-rank test, P = 0.022) and a higher relapse rate in the first two years (odds ratio 1.1 , [95% CI 0.8-2.1]; P = 0.04), regardless of sex, age of onset, phenotype and disease-modifying treatment. The modified McDonald criteria was non-inferior to the 2017 McDonald criteria in terms of sensitivity (81% vs.77%, P > 0.05), specificity (48% vs.58%, P > 0.05) and accuracy (63% vs.66%, P > 0.05).

An elevated IgG index was diagnostic of MS and predictive of its early activity. IgG index could be an OCB substitute in application of the 2017 McDonald criteria.