Barts-MS rose-tinted-odometer: ★★ (amber; a sleep deprived colour somewhere between yellow and orange)
It has become clear that the anti-CD20 therapies are more than just anti-B-cell therapies. Minority populations of both CD4+ and CD8+ T-cells and NK-cells express CD20 and are depleted after both rituximab and ocrelizumab treatment.
It looks as if ocrelizumab may be more effective in deleting this population of cells and may explain why herpes zoster or shingles is more common after ocrelizumab, compared to rituximab, than what you would expect based on its putative B-cell only targeting effect. The mild depletion of this population of cells may also explain why pwMS on ocrelizumab are at higher risk of getting COVID-19 and severe COVID-19.
The study below shows that this population of cells express a so-called CTL or cytotoxic phenotype that fits in with the zoster and COVID-19 data. This also raises concerns that just maybe peripheral tumour immune surveillance is also compromised on anti-CD20 therapies. The tumour signal however is likely to be small as a large secondary cancer signal would likely have emerged already on the anti-CD20s.
More topical is the role these CD20-expressing T-cells play in vaccine responses. If they are important in vaccine immunity then patients with MS on anti-CD20 therapies who lack this population of T-cells may not develop adequate T-cell immunity in response to vaccination. We won’t have long to wait for the latter data as many immunology laboratories are busy trying to get their T-cell vaccine data out as soon as possible.
So yes there is much more to the immunology of anti-CD20 therapy than simple B-cell depletion. Could the T-cell compartment targeted by anti-Cd20 therapies be as important or more important than the B-cell compartment? There is so much more to learn about how MS DMTs really work, in particular the anti-CD20 therapies.
Boldrini et al. Cytotoxic profile of CD3+CD20+ T cells in progressive multiple sclerosis. Mult Scler Relat Disord. 2021 May 7;52:103013.
Recently, it was shown that highly effective anti-CD20 therapies used for MS patients not only deplete CD20+ B cells, but also a small subset of T cells expressing CD20 surface marker (CD3+CD20+ T cells). Here we demonstrated that, in progressive MS patients, CD3+CD20+ T cells share the ability to express cytotoxic factors such as perforin and serine-protease granzyme-B (GzmB), classically associated with CD8+ T cells functionality. Beyond it, cluster analyses show that a set of activation markers and transcriptional factors related with CD8 effector program are also expressed in CD3+CD20+ T cells. Further characterization of surface and functional markers from CD3+CD20+ T subsets may be helpful for development of new therapeutic strategies mainly for progressive MS patients, as well as for assessing pathophysiological effects of highly effective anti-CD20 therapies.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.