Ocrelizumab modulates the IL-2 signaling pathway and associated lncRNAs in multiple sclerosis

Ocrelizumab, a CD20⁺ B cell-depleting monoclonal antibody, is widely used in multiple sclerosis (MS), yet its molecular impact on immune regulation remains incompletely defined. Given the importance of the interleukin-2 (IL-2) signaling axis in immune tolerance, we investigated the expression of key genes in this pathway, and their associated long non-coding RNAs in an Iranian cohort of relapsing-remitting MS patients. Peripheral Blood Mononuclear Cells (PBMC) from 20 untreated patients, 20 Ocrelizumab (Xacrel®)-treated stable RRMS patients for whom at least six months had passed since the last dose, and 20 healthy controls were analyzed by RT-PCR. Treatment resulted in reduced IL2RA and FOXP3 but not IL2 expression levels and normalization of FLICR and RP11-536 K7.5 levels in MS patients. Correlation analysis revealed a strong IL2RA-FOXP3 association and inverse IL2RA-RP11-536 K7.5 correlation in treated patients. Lower IL2RA and RP11-536 K7.5 levels correlated with higher EDSS scores. ROC analysis highlighted IL2, IL2RA, and FOXP3 as strong classifiers in treated patients, and RP11-536 K7.5 in untreated cases. FOXP3 expression positively correlates with the number of Ocrelizumab infusions, indicating reinforcement of regulatory T-cell activity with ongoing therapy. These findings highlight IL-2 pathway modulation and lncRNA regulation as therapeutic effects of Ocrelizumab.