Early B Cells Repopulation in Multiple Sclerosis Patients Treated with Rituximab is Not Predictive of a Risk of Relapse or Clinical Progression

Background: It is currently unknown whether early B cell reconstitution (EBR) in MS patients under rituximab is associated with a risk of relapse or progression.

Objectives: Analyzing EBR in rituximab-treated patients and its putative association with clinical findings.

Methods: Prospective lymphocytes immunophenotyping was performed in a monocentric cohort of MS patients treated by rituximab for 2 years. EBR was defined when B cells concentration was > 5 cells/mm3. B cell subsets were retrospectively associated with clinical data. Clinical and radiological monitoring included relapses, EDSS (Expanded Disability Status Scale), SDMT (Symbol Digit Modalities Test), and MRI.

Results: 182 patients were analyzed (61 remitting-relapsing and 121 progressive-active). 38.5% experienced EBR at least once, but very few (7/182) showed systematic reconstitution. Most patients remained stable upon treatment, regardless of the occurrence of EBR. Dynamics of B cell reconstitution featured increased naïve/transitional B cells, and decreased memory subsets. Homeostasis of the B cell compartment differed at baseline between patients experiencing or not EBR upon treatment. In patients with EBR, reciprocal dynamics of transitional and pro-inflammatory double-negative B cell subsets was associated with better response to rituximab treatment.

Conclusion: EBR is common in rituximab-treated MS patients and is not associated with clinical disease activity. EBR in the peripheral blood may reflect regulatory immunological phenomena in subgroup of patients.