Longitudinal changes in serum protein levels are associated with disability progression in multiple sclerosis

Early identification of patients with multiple sclerosis (MS) at risk of transitioning from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) remains a major clinical challenge. Although magnetic resonance imaging (MRI) is widely used to monitor disease activity, imaging markers alone may not adequately predict progression. The identification of accessible biochemical markers associated with disability progression could improve long-term monitoring.

This retrospective observational study evaluated clinical, radiological, and biochemical parameters in 45 MS patients followed at a single tertiary center. Twenty-three patients remained in the RRMS phase, while 22 developed SPMS. Cerebrospinal fluid (CSF) biomarkers obtained at diagnosis and serum biomarkers measured at two time points separated by two years were analyzed. Group comparisons used non-parametric tests, and associations with disability were assessed using Spearman correlation.

Serum albumin and total protein levels measured two years before progression were significantly lower in patients who later developed SPMS compared with those who remained RRMS. Creatinine and ferritin did not differ between groups. In RRMS patients, ferritin levels decreased significantly over time, whereas albumin and total protein remained stable. CSF IgG index values tended to be higher in patients who later developed SPMS, without reaching statistical significance. MRI activity was not associated with progression. Total serum protein levels were inversely correlated with EDSS scores.

Lower serum protein levels may precede clinical transition to SPMS and reflect processes related to disability progression. Despite not being independent predictors, their accessibility supports their potential role in longitudinal monitoring strategies.