Depleting antibodies work because they deplete. So check white blood cells and they drop. Natalizumab keeps cells out of the brain and so white blood cells will increase lymphocytes go up by an average of 1.8 x 10*9 cells per litre but on the whole they stay within the normal range 1 to 4.9–4.5 x 10*9 and so I have suggested that one should look at CD19+ B cell as they elevate above normal on the whole….
Each dot is one person, green is the normal range you can see at 3 months M3 most people increase but only about 7 people are above normal range
its not the T cells =CD3 positive it is the B cells
Graphs Reproduced from Kaufmann M, Haase R, Proschmann U, Ziemssen T, Akgün K. Real-World Lab Data in Natalizumab Treated Multiple Sclerosis Patients Up to 6 Years Long-Term Follow Up. Front Neurol. 2018 ;9:1071 under creative commons CC-BY
However, some company people don’t really believe me and so won’t help me work out the rules to determine when natalizumab is working, maybe because they don’t want us to say that natalizumab doesn’t work (indicated by a lack of increase of white blood cells) for a significant number of people for some it never really works and they are at elevated risk of disease activity and for others it takes about 6 months for it to elevate the white blood cells. You don’t need to do work you can simply read to work this out. However this new paper goes further and suggests that memory B cells (IgD-/+, CD19+, CD20+, CD27+) and to a lesser extent double Negative (IgD-, CD27-) memory cells. They go up without overlap.
reproducted from Curtin R, Velmurugu Y, Dibba F, Hao Y, Nyovanie S, Lopez A, Mieles D, Ng C, Perdomo K, Scott N, Lewin JB, Avila RL, Smrtka J, Patskovsky Y, Howard J, Silverman GJ, Krogsgaard M. Natalizumab and fumarate treatment differentially modulate CD4+ T cell and B cell subtypes in multiple sclerosis patients without impacting durable COVID-19 vaccine responses. Front Immunol. 2025;16:1568157 under creative commons CY-BB
We know natalizumab and the fumarates dont block COVID vaccination by the reason why people do respond to natalizumab if that they rapidly induce anti-drug antibodies. These appear within 4-8 weeks and then subside over the rest of the year once they are gone the drug can work.
Curtin R, Velmurugu Y, Dibba F, Hao Y, Nyovanie S, Lopez A, Mieles D, Ng C, Perdomo K, Scott N, Lewin JB, Avila RL, Smrtka J, Patskovsky Y, Howard J, Silverman GJ, Krogsgaard M. Natalizumab and fumarate treatment differentially modulate CD4+ T cell and B cell subtypes in multiple sclerosis patients without impacting durable COVID-19 vaccine responses. Front Immunol. 2025 Nov 19;16:1568157.
Background: There is a greater risk of complications from severe COVID-19 in immunocompromised patients with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs), as well as a diminished vaccine response.
Methods: In this exploratory, observational study, we recruited 28 patients with Relapsing Remitting MS (RRMS, n=24) or Secondary Progressive MS (SPMS, n=4), that were receiving treatment with either natalizumab or fumarates (diroximel or dimethyl) prior to baseline sample collection. Blood samples were collected before vaccination (baseline), between 4 weeks and 6 months post vaccination, and post booster administration. A multiplex bead immunoassay (MBI) was used to measure anti-Spike IgG, while IFNγ and IL-2 ELISpot assays were used to determine T cell activation. A 35-color spectral flow cytometry panel was used to phenotype bulk B and T cells and SARS-CoV-2-specific T cells, while dimensionality reduction was performed for further phenotypic analysis.
Results: We observed a significantly increased absolute lymphocyte count (ALC) (p=0.0003) in natalizumab-treated pwMS when compared to fumarate-treated pwMS primarily due to increased circulating CD19+ B cells. Fumarate-treated pwMS exhibited a diminished Th1/Th2 ratio when compared to natalizumab-treated pwMS (p=0.0004) or healthy controls (p=0.0745), while natalizumab treatment marginally increased the Th1/Th2 ratio compared to healthy controls (p=0.1311). The observed increase in B cells in natalizumab-treated pwMS were predominantly memory B cells, and double negative (DN) B cells. However, no significant differences between the treatment groups were seen in terms of Spike IgG titers following the initial vaccination course or booster dose, nor in SARS-CoV-2-specific CD4+ responses, all of which remained robust for at least 6 months post-vaccination. The magnitude of humoral and cellular immune responses in both treatment groups were comparable to vaccinated healthy controls. Additionally, SARS-CoV-2 spike-specific CD4+ T cell phenotyping revealed a Th2 dominant response to booster dose in natalizumab-treated pwMS (p=0.0485) but not fumarate-treated pwMS.
Conclusion: pwMS treated with natalizumab or fumarates exhibit similarly robust and durable SARS-CoV-2 specific T cell and humoral responses following vaccination and booster dose. DMT-treated pwMS showing comparable responses to healthy individuals following initial vaccination supports the notion that treatment with these specific DMTs does not diminish strong, long-lasting immunity conferred by COVID-19 vaccination, despite the phenotypic differences modulated by each thera
Source: multiple-sclerosis-research.org