- David Baker, Charles AK Roberts, Gareth Pryce, Angray S Kang
- Monica Marta, Saul Reyes,Klaus Schmierer, Gavin Giovannoni
- Sandra Amor. Clin Exp Immunol https://doi.org/10.1111/cei.13495
Although most autoimmune diseases are considered to be CD4 T‐cell or antibody‐mediated, many respond to CD20‐depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab, ofatumumab that are used in cancer, rheumatoid arthritis and off‐label in a large number of other autoimmunities, and ocrelizumab in multiple sclerosis. Recently, the COVID‐19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID‐19, it was hypothesised that whilst B‐cell depletion should not necessarily expose people to severe SARS‐CoV‐2‐related issues, it may inhibit protective immunity following infection and vaccination. As such, drug‐induced B‐cell subset inhibition that controls at least some autoimmunities, would not influence innate and CD8 T‐cell responses, which are central to SARS‐CoV‐2 elimination, nor the hyper‐coagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS‐CoV‐2 infected, CD20‐depleted people with autoimmunity, have recovered. However, protective neutralising‐antibody and vaccination responses are predicted to be blunted, until naïve B‐cells repopulate, based on B‐cell repopulation‐kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose‐interruption to maintain inflammatory disease control, whilst allowing effective vaccination against SARS‐CoV‐29, if and when an effective vaccine is available.
So now we know ocelizumab induces an inhibition of relapse that appears to last at least 18 months in most people and if we look at memory B cells they are gone for at least 18 months in most people. So if you are asked to delay your dose for a while a biology is present that can explain the reason why it may not be a major concern to do this. The data looks pretty solid up to 12 months at the very least. As you can see the effect on CD4 cells is very limited and the suggestion that this is why ocrelizumab is working, seems to me to be a pretty desparate piece of science, yet it is a belief that has to be accomodated every time you talk about B cells. Turn it around and you talk about fingolimod and an action onT cells and no-one bats an eye lide that B cells do not get mentioned, Talk about cladribine and you are stuck with the its all regulation babble. Why make it complicated when it can be simple?. I suspect there are too many vested interests and the science advisers are happy to make you think it is all complicated, other wise they wouldnt get enless grants on T regs this and Th numpty that. The evidence mounts, but I guess we have to wait until the opinion leaders make the discovery….I will probably have been put out to pasture by then:-(.
However this view has been challenged…I need to read and come back to you on this
The other thing this paper sowes that if you believe that you need a B cell response to be vaccine ready…you will be awaiting for some time, if fact you will be waiting forever if you dose every 6 months. However,the good news is I think the T cells are more important, until I am proved wrong. So maybe less to worry about.
Why say this?
It is evident that many people infected with SARS-CoV-2 do not make an antibody response and recover. Importantly these people make a T cell response. In the SARS epidemic the B cell response disappeared long before the T cell response that was still detectable whenlooked for over a decade later.
Thanks to the manufacturer and http://www.ClinicalStudyDataRequest.com for making the data available
COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases.Baker D, Roberts CA, Pryce G, Kang AS, Marta M, Reyes S, Schmierer K, Giovannoni G, Amor S.Clin Exp Immunol. 2020 Jul 16. doi: 10.1111/cei.13495. Online ahead of print
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