Dr Dooley will be happy that their uncited work from 2016 has been repeated….MS drugs affect memory B cells!

D

Part of the scientific process is repetition, but at some point in time you need to believe it and move one. This study is Open access and so you can read it, but it is further supportive evidence of the memory B cell hypothesis

Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis.Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. EBioMedicine. 2017; 16:41-50

This data has been seen before as reported by

Immunologic profiles of multiple sclerosis treatments reveal shared early B cell alterations.Dooley J, Pauwels I, Franckaert D, Smets I, Garcia-Perez JE, Hilven K, Danso-Abeam D, Terbeek J, Nguyen AT, De Muynck L, Decallonne B, Dubois B, Liston A, Goris A.Neurol Neuroimmunol Neuroinflamm. 2016 May 10;3(4):e240. 

However, the paper states of “various MS treatments exert differential effects on B cell subsets but the exact roles of B cells during the different drugs’ mode of action remain inconclusive”…So we don’t know where to look.

“With the exception of one study, several studies have shown an increased percentage of naïve B cells and decreased percentage of memory B cells in the peripheral blood, especially during relapse . As a possible explanation it has been proposed, that memory B cells are directed to the site of inflammation in active disease. Indeed, increased values of mainly memory B cells and plasmablasts are found in the cerebrospinal fluid (CSF) which persist during MS disease course. However, B cell trafficking across the blood-brain-barrier and B cell maturation within the CNS show complex patterns and the precise involvement of the different B cell subsets in MS pathology still remains unclear”.

Why is it so unclear…because it is all so confusing!. However, if you don’t know where to look you put your crown jewels in a publishing cuboard so people don’t know where to look. I bet this will happen when the data on ozanimod posanimod or cladribine tablets eventually surface. I also bet the memory B cellls will be markedly depleted, but this important message will be lost in a sea of T cell and T reg stuff…..Yawn!

So the introduction goes something like this. “The mechanism of *****imod was unknown” Then you get something like this

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Kemmerer et al 2020

But we know that you need to look at absolute numbers not percentages as shown above. You could have an introduction like this. “it was hypothesised that *****imod would reduce the numbers of memory B cells” Then you shown this.

Kemmerer et al 2020

The light goes on and everything is simple. You get it and now you can see why beta interferon and glatiramer aren’t that effective in most people and GA is bottom of the efficacy pile and fingolimod is more active than DMF. You understand why rebound occurs when you stop natalizumab and don’t switch to an effective therapy. However, people won’t do this because they want to think that it is all so complicated,

Differential effects of disease modifying drugs on peripheral blood B cell subsets: A cross sectional study in multiple sclerosis patients treated with interferon-β, glatiramer acetate, dimethyl fumarate, fingolimod or natalizumab.Kemmerer CL, Pernpeintner V, Ruschil C, Abdelhak A, Scholl M, Ziemann U, Krumbholz M, Hemmer B, Kowarik MC.PLoS One. 2020 Jul 27;15(7):e0235449. doi: 10.1371/journal.pone.0235449

Background: Several disease modifying drugs (DMDs) have been approved for the treatment of multiple sclerosis (MS), however, little is known about their differential impact on peripheral blood (PB) B cell subsets.

Methods: We performed a cross sectional study on PB B cells in MS patients treated with interferon-β (n = 25), glatiramer acetate (n = 19), dimethyl fumarate (n = 15), fingolimod (n = 16) or natalizumab (n = 22), untreated MS patients (n = 20), and in patients with non-inflammatory neurological diseases (n = 12). Besides analyzing routine laboratory data, flow cytometry was performed to analyze naïve B cells (CD19+CD20+CD27-IgD+), non-class switched (CD19+CD20+CD27+IgD+) and class-switched memory B cells (CD19+CD20+CD27+IgD-), double negative B cells (CD19+CD20lowCD27-IgD-) and plasmablasts (CD19+CD20lowCD27+CD38++).

Results: Treatment associated changes were found for the overall B cell pool as well as for all B cell subsets. Natalizumab increased absolute numbers and percentage of all B cells mainly by expanding the memory B cell pool. Fingolimod decreased absolute numbers of all B cell subsets and the percentage of total B cells. Fingolimod, dimethyl fumarate and interferon-β treatments were associated with an increase in the fraction of naïve B cells while class switched and non-class switched memory B cells showed decreased percentages.

Conclusion: Our results highlight differential effects of DMDs on the PB B cell compartment. Across the examined treatments, a decreased percentage of memory B cells was found in dimethyl fumarate, interferon-β and fingolimod treated patients which might contribute to the drugs’ mode of action in MS. Further studies are necessary to decipher the exact role of B cell subsets during MS pathogenesis.

Yep the discussion mentions what memory B cells may do, but surely it should be a starting point and not an ending point? OK rant over, the altmetric link from hell when the author finds it, but you need evidence….I’m sure my colleagues will and won’t know where to look!….enjoy those cladrimod papers when they arrive.

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MouseDoctor

5 comments

      • RESULTS Alemtuzumab depleted CD4+ T cells by more than 95%, including regulatory cells
        (−80%) and CD8+ T cells (>80% depletion), which remained well below reference levels
        throughout the trials

        Well if 95% is just a little i sugest get in touch with the paper author 🙂

        David Baker; Samuel S. Herrod, Cesar Alvarez-Gonzalez, Gavin Giovannoni; Klaus Schmierer Interpreting Lymphocyte Reconstitution Data From the Pivotal Phase 3 Trials of Alemtuzumab. JAMA Neurol. Published online June 12, 2017. doi:10.1001/jamaneurol.2017.0676

        Wait wait

        Its you 🙂

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