Effects of Ofatumumab Treatment on Immune Cells Landscape in Patients With Relapsing-remitting Multiple Sclerosis
Shu Yang1, Tianxiang Zhang1, Bin Feng1, Chao Zhang1
1Tianjin Medical University General Hospital
Objective:
This study aimed to explore the change of immune cell landscape after ofatumumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS).
Background:
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. Increasing evidence indicate that the bidirectional interactions among T cells, B cells and myeloid cells, involve in the pathogenesis of MS. Ofatumumab, a fully humanized anti-CD20 monoclonal antibody, is proved to be highly efficient in patients with RRMS. However, the dynamics of immune cells in patients after receiving ofatumumab treatment have not been fully elucidated.
Design/Methods:
17 patients diagnosed RRMS were enrolled in this uncontrolled, prospective, observational cohort study (OMNISCIENCE, NCT05414487). Participants received ofatumumab treatment over an observational period of 12 month. The dynamics of immune cell subsets in RRMS patients was detected by mass cytometry (CyTOF) at baseline and after 12 months of ofatumumab treatment.
Results:
In our study, the frequency of naïve T cells and CD25+Foxp3+ regulatory T cells (Tregs) were increased in peripheral blood of patients with RRMS after receiving ofatumumab treatment, while effector memory CD4 and CD8 T cells decreased after treatment. Ofatumumab significantly upregulated the expression of immune checkpoint, PD-1 and CTLA-4 on T cells. However, T cell activation marker CD69, inducible costimulatory molecule ICOS, and chemokine receptor CXCR3 and CXCR5 were inhibited after ofatumumab treatment. Moreover, the frequency of peripheral monocytes and conventional dendritic cell (cDC) were elevated in patients with RRMS after receiving ofatumumab. High expression of HLA-DR and costimulatory molecule CD86 on these myeloid cells were detected.
Conclusions:
Ofatumumab treatment altered the frequency and phenotype of T cell subsets and myeloid cells, indicating its effect to reduce T cell effector function and migration potential, and to potentiate antigen presentation capability by monocytes and dendritic cells.