Proteomics confirms immune stabilizing effects of narrowband UVB treatment in patients with clinically isolated syndrome and multiple sclerosis

Background: Multiple sclerosis (MS) demonstrates a latitude gradient in prevalence and severity, implicating ultraviolet B (UVB) exposure and photoimmune mechanisms in disease risk and progression. While narrowband (NB)-UVB phototherapy has long stabilized inflammation in dermatology, its systemic immunomodulatory effects in MS remain incompletely defined. Objective To characterize the photoimmune impact of NB-UVB in clinically isolated syndrome (CIS)/MS patients, leveraging untargeted and targeted proteomic analysis including the Octave Multiple Sclerosis Disease Activity Score. Methods In the PhoCIS trial, CIS patients were randomized to NB-UVB (3 × /week for 8 weeks) or standard care. Serum samples from baseline and day 90 were analyzed using the Olink Target 96 Inflammation panel (untargeted) and the clinically validated MS Disease Activity (MSDA) test panel (targeted). Statistical analyses compared differences within and between-groups. Results Comparing the difference from baseline to day 90, the NB-UVB cohort had significant downregulation in 23 of 92 inflammatory proteins, while the Controls had no changes. Targeted MSDA scores confirmed similar differentially significant reductions in general disease activity and severity, and within the component neuroinflammation, immunomodulation, and neuroaxonal integrity scores. Conclusion NB-UVB caused broad and coordinated reductions in untargeted and targeted inflammatory proteins. These effects support NB-UVB as a promising immunomodulatory strategy in MS in both general inflammation and MS-specific activity, as well as consideration of inflammatory markers and the MS Disease Activity Score as surrogate endpoints in future trials.