Ocrelizumab and T-cells


Ocrelizumab depletes T-lymphocytes more than rituximab in multiple sclerosis.
Capasso N, Nozzolillo A, Scalia G, Lanzillo R, Carotenuto A, De Angelis M, Petruzzo M, Saccà F, Russo CV, Brescia Morra V, Moccia M.Mult Scler Relat Disord. 2021 Jan 28;49:102802. doi: 10.1016/j.msard.2021.102802. 

Background: We aim to directly compare changes in lymphocyte subpopulations between chimeric (rituximab) and humanised (ocrelizumab) anti-CD20 antibodies in multiple sclerosis (MS).

Methods: In this retrospective analysis of prospectively collected data, we included 88 patients with MS, treated with rituximab (n=50) or ocrelizumab (n=38). We used flow cytometry in the peripheral blood to count total lymphocytes and lymphocytes expressing different phenotypic markers (CD4, CD8, CD19, CD20, CD4/CD8 ratio), before treatment and after 1, 3 and 6 months.

Results: After 1, 3 and 6 months, patients treated with rituximab and with ocrelizumab were similar in total lymphocyte count, CD19 lymphocytes, CD20 lymphocytes and CD4/CD8 ratio. However, patients treated with ocrelizumab presented with lower CD4 T lymphocytes and CD8 T lymphocytes after 1, 3 and 6 months (all p<0.05). No between-treatment difference in EDSS progression was found.

Discussion: B-cell levels in the peripheral blood were equally decreased by rituximab and ocrelizumab. On the contrary, CD4 and CD8 T lymphocyte reduction was more pronounced in ocrelizumab, when compared with rituximab, suggesting a broader immunomodulatory effect for the humanised antibody to be confirmed and correlated with clinical efficacy in the long term.

So what does this say, there is no treatment differences in people on ocrelizumab and rituximab. There are differences in T cell with ocrelizumab being more inhibitory….therefore the influences of T cells is irrelevant as it makes no treatment influence. Does it block vaccine responses more than rituximab. We simple have to do the studies.

About the author



  • Simply dosing IvIg, polyclonal, human IgG, increases number of circulating Treg in humans. I see the the authors refer to ublituximab has a similar effect. In my thesis I hypothesis such Treg induction is due to preserved areas of IgG structure, structures present to keep T cell tolerance towards IgG in check (check it out if you have an awful lot of spare time: duo.uio.no/handle/10852/80722). Could a similar mechanism be operating here? Does the changes to Ocrelizumab variable regions more efficiently generate Treg responses, due to humanization? Or is it just a dosing/efficacy thing, where more B cells killed equals fewer

    Pity their panel did not include Treg or memory markers, might have been an interesting find.

      • Yeah, the clinical part may not be due to T cells at all. My point here was simply regarding the differences in number of T cells observed after dosing. Could be due to killing by mAb (i.e. the few CD20+ T cells..), could be indirect through killing B cells (limiting expansion/activation), could be generation of Tregs (suppression), etc.

      • I remember the Stockholm-standoff about that paper (NNIM-meeting) 🙂 I struggle a bit to understand why RASGRP2 is the obvious answer to the autoproliferation. That being said, I consider the main findings (autoproliferation) excellent quantitative evidence for one of the most used sentences in MS immunopathology reviews (“dysregulated immune system”).

        I discuss the possible relation of autoproliferation to Ig variable regions in the thesis as well.

        • Bit quick on the trigger, the standoff was about the predecessor-paper. The HLA-DR-SP reactivity is nicely shown, but cross-reactivity among T cells is not new. The bottom line is that something is off with the tolerance in these patients (and all patients with AID).

  • No between-treatment difference in EDSS progression was found.

    6 months is enough to see a diference in edss ?


  • The godfather of b cells reference the study of Wang et al

    HLA-DR15 Molecules Jointly Shape an Autoreactive
    T Cell Repertoire in Multiple Sclerosi

    And says

    ” It is quite remarkable that a substantial
    proportion of these peptides presented
    by class II HLA molecules on B cells appear to
    be fragments of the class II molecules themselves.”

    Antigen Presentation by B Cells in Multiple Sclerosis

    DOI: 10.1056/NEJMcibr2032177

    Does this makes for a clear autoimmune process in ms’


By MouseDoctor



Recent Posts

Recent Comments