It has been suggested that the cervical lymph glands in the neck act as the draining site from the brain. Here they are looking at lymph node biopsies to see what happens following B cell depletion and following natalizumab. The take home message is that the B cells increase after natalizumab but decreases after B cell depletion. This may be expected because this is what happens in the blood. However this will be interesting because they have lumped rituximab and ofatumumab together. This is interesting because they are given at different doses, frequencies and routes. Rituximab is given via the blood and it will quickly go every where. Ofatumumab is given under the skin and must drain into the lymph glands and then travel into the lymph ducts in the armpits to get into the blood it will then do to the lymph glands in the neck. Those draining the skin won’t connect to those in the neck. So the the suggestion that the glands are cleared of B cells like following rituximab is interesting as the amount reaching the blood with rituximab and ofatumumab are very different if we are to believe the reports. That plasmablasts drop says that the effects are not direct as plasmablasts do not express CD20 and should not be depleted. This study is preliminary but by understanding what goes on in the lymph glands currently suggests the doses are doing similar things
Abstract Number: 1221/P1625 Abstract Number: 1221/P1625 Disease-modifying therapies change the cellular composition of deep cervical lymph nodes of patients with multiple sclerosis Disease-modifying therapies change the cellular composition of deep cervical lymph nodes of patients with multiple sclerosis
Nea Kreivi et al.
Introduction: We previously showed an altered lymphocyte compartment within the deep cervical lymph nodes (dcLNs) of patients with MS (pwMS) at the diagnostic phase, before immunotherapy, compared to healthy controls. Whether disease-modifying therapies (DMTs) change the cellular composition of dcLNs, where lymphocyte targeting of central nervous system is suggested to be initiated, has not been explored.
Objectives/Aims: Objectives/Aims: To investigate the dcLN immune cell subsets by frequency distributions of pwMS before and after DMTs.
Methods:We used fine needle aspirations (FNAs) of dcLNs followed by single-cell RNA sequencing (scRNAseq). We studied five patients across three treatment groups: two receiving dimethyl fumarate, two on rituximab or ofatumumab (B-cell depleting), and one on natalizumab (leukocyte trafficking inhibitor).
We compared scRNAseq data sampled pre-treatment and at a stable follow-up time point from the same individual.
Results: We observed significant differences in the cell type frequency distributions. B cell depleting therapies rituximab and ofatumumab produced significant decreases in the proportions of memory B cells, naïve B cells, germinal center (GC) B cells and plasmablasts. At the same time, significant increases in T follicular helper (Tfh)-like cells, natural killer (NK)-like CD8, NK cells, effector CD4, monocytes, and T follicular regulatory (Tfr) cell proportions were seen. In contrast, natalizumab produced significant increases in GC B cells, memory B cells and GC Tfh within the dcLN. Decreases were observed in T regulatory (Treg) cells, plasmablasts, and naïve CD8s and CD4s. PwMS treated with dimethyl fumarate showed significant increases in naïve CD4, NK cells and naïve CD8 T cell populations, while decreases were observed in proportions of memory B cells, NK-like CD8s, effector CD4s, memory CD8s, GC B cells and Tfh cells.
Conclusion: Our study demonstrates intranodal effects of DMTs, where B cell depletion reaches the dcLNs, as has been shown for patients with neuromyelitis optica. Natalizumab, on the contrast, appears to amplify the alterations of the intranodal compartment present at the diagnostic phase, concordant with the mechanism of action.
Source: multiple-sclerosis-research.org