Assessing Peripheral Blood Biomarkers and Predictive Patterns in Multiple Sclerosis Using Cytokines and Immune Gene Expression Profiles in Ocrelizumab-Treated Patients: Tracking Tumor Necrosis Factor

Ocrelizumab, a humanized monoclonal anti-CD20 and B cell-depleting antibody, is a disease-modifying therapy for multiple sclerosis (MS), a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. However, reliable predictive biomarkers of ocrelizumab's effectiveness, such as cytokine expression profiles in peripheral blood mononuclear cells (PBMCs), are lacking. The aim of this study was to identify immunological biomarkers of ocrelizumab treatment response in MS patients, during a two-year follow-up. mRNA expression for specific immune molecules in PBMCs was measured, and consequently correlated with the clinical and radiological parameters of disease activity. PBMCs were obtained from 80 MS patients (35 with relapsing-remitting MS-RRMS and 45 with primary progressive-PPMS), immediately before initiating ocrelizumab treatment and thereafter every 6 months (before the administration of the next dose of ocrelizumab). Expression of the B cell marker <i>CD19</i>; the pro-inflammatory cytokines interleukin (<i>IL</i>)<i>1B</i>, <i>IL6</i>, and tumor necrosis factor (<i>TNF</i>); and a costimulatory cell marker <i>CD86</i> were determined. In both RMS and PPMS patients treated with ocrelizumab, higher baseline expression of <i>TNF</i> was statistically significantly associated with an increased risk of developing evidence of disease activity and a greater likelihood of disability progression, at month 24. This result implies that PBMCs' <i>TNF</i> mRNA expression might be potentially considered as a prognostic biomarker of ocrelizumab effectiveness in MS patients. However, further studies comprising large cohorts and additional immunological parameters are warranted.