“However, some subsets of pro-inflammatory B-cells were increased, indicating that some B-cells can “promptly arise” after Ocrevus treatment and that “anti-CD20 treatment does not reconstitute a fully healthy immune system or re-establish immune tolerance in all patients, supporting the need for retreatment,” the team wrote. An explanation?
The study showed what would be expected. You give ocrelizumab and that depletes naive and memory B cells and then you get a few immatutre/transitional B cells repopulating after depletion and these produce a cytokine called interleukin-ten. There was no major impact on T cell numbers but the of T cells remaining have a less activated signature, but hey disease is being controlled. You get fewer lesions (so you get less gadolinium) and as a consequence of that you get less nerve damage. However, there were also relative increases in GM-CSF- and
IL-6-producing B cells so let’s keep treating with ocrelizumab.
They say “no significant differences were observed in the total cell numbers (of T cells) but CD20T were reduced
Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS. José I. Fernández-Velasco, Jens Kuhle, Enric Monreal, Virginia Meca-Lallana, José Meca-Lallana, Guillermo Izquierdo, Francisco Gascón-Giménez, Susana Sainz de la Maza, Paulette E. Walo-Delgado, Aleksandra Maceski, Eulalia Rodríguez-Martín, Ernesto Roldán, Noelia Villarrubia, Albert Saiz, Yolanda Blanco, Pedro Sánchez, Ester Carreón-Guarnizo, Yolanda Aladro, Luis Brieva, Cristina Íñiguez, Inés González-Suárez, Luis A. Rodríguez de Antonio, Jaime Masjuan, Lucienne Costa-Frossard, Luisa M. Villar Neurology Neuroinflammation neuroimmunology 2021, DOI: https://doi.org/10.1212/NXI.0000000000000940
Objective To analyze the changes induced by ocrelizumab in blood immune cells of patients with primary progressive MS (PPMS).
Methods In this multicenter prospective study including 53 patients with PPMS who initiated ocrelizumab treatment, we determined effector, memory, and regulatory cells by flow cytometry at baseline and after 6 months of therapy. Wilcoxon matched paired tests were used to assess differences between baseline and 6 months’ results. p Values were corrected using the Bonferroni test.
Results Ocrelizumab reduced the numbers of naive and memory B cells (p < 0.0001) and those of B cells producing interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNFα) (p < 0.0001 in all cases). By contrast, the proportions of plasmablasts and B cells producing GM-CSF and TNFα increased significantly, suggesting the need for treatment continuation. We also observed a decrease in CD20+ T-cell numbers (p < 0.0001) and percentages (p < 0.0001), and a clear remodeling of the T-cell compartment characterized by relative increases of the naive/effector ratios in CD4+ (p = 0.002) and CD8+ (p = 0.002) T cells and relative decreases of CD4+ (p = 0.03) and CD8+ (p = 0.004) T cells producing interferon-gamma. Total monocyte numbers increased (p = 0.002), but no changes were observed in those producing inflammatory cytokines. The immunologic variations were associated with a reduction of serum neurofilament light chain (sNfL) levels (p = 0.008). The reduction was observed in patients with Gd-enhanced lesions at baseline and in Gd− patients with baseline sNfL >10 pg/mL.
Conclusions In PPMS, effector B-cell depletion changed T-cell response toward a low inflammatory profile, resulting in decreased sNfL levels.
So further evidence that sNfL is a marker of neuroinflammatory activity