Sunday, 20 November 2016

Aging B cells in MS

Claes N, Fraussen J, Vanheusden M, Hellings N, Stinissen P, Van Wijmeersch B, Hupperts R, Somers V.Age-Associated B Cells with Proinflammatory Characteristics Are Expanded in a Proportion of Multiple Sclerosis Patients. J Immunol. 2016 Nov 11. pii: 1502448. [Epub ahead of print]
Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD-CD27- (double negative, DN) and CD21-CD11c+(CD21low) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21low B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21low (9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients. The majority of DN B cells had an IgG+ memory phenotype, whereas CD21low B cells consisted of a mixed population of CD27- naive, CD27+ memory, IgG+, and IgM+ cells. DN B cells showed similar (MS patients) or increased (healthy donors) MHC-II expression as class-switched memory B cells and intermediate costimulatory molecule expression between naive and class-switched memory B cells, indicating their potential to induce (proinflammatory) T cell responses. Further, DN B cells produced proinflammatory and cytotoxic cytokines following ex vivo stimulation. Increased frequencies of DN and CD21low B cells were found in the cerebrospinal fluid of MS patients compared with paired peripheral blood. In conclusion, a proportion of MS patients showed increased peripheral expansions of age-associated B cells. DN and CD21low B cell frequencies were further increased in MS cerebrospinal fluid. These cells could contribute to inflammation by induction of T cell responses and the production of proinflammatory cytokines

What does this all mean, well not much I think as the changes only occur at best in about 25% of pwMS, but I think 2017 is going to be the year of the B cell as ocrelizumab hopefully gets a licence for treatment of MS, either that or rituximab use develops.


What are B cells?
These are the cells that produce antibodies and are made in the bone marrow. There are loads of diferent types of B cell, which can be recognised by their surface marker expressssion. The cell that produces MS are called plasma cells. These are made in germinal centres (GC) in lymph glands






So in the germinal centres you find the plasma cells,  they come from  cells that develop from the stem cell and express markers along the way. The mature cells are also known as naive cells and can be recognised by the expression of lack of expression of certain markers like CD21  and CD27






The markers are varied depending on the stage of development

Anti CD20 is what ocrelizumab and rituximab hits

3 comments:


  1. I have an open letter to MD and professor Gavin G.

    For some reason, you underestimate the risks with Ocrelizumab - it is far to much blue sky (sorry) opinions aired about this, to my view, risky MS-agent.

    Apart from all these cancer cases in the ORATORIO / PPMS trial (2.3% vs 0.8%) and also worrying 6 cases of breast cancer vs 0 in placebo - if you include the RRMS trial (Opera I/Opera II), it would be good to look at the history of this Ocrelizumab - its footprints in the past.

    Ocrelizumab was halted in 2009/2010 both in Lupus and in RA due to several fatal deaths. It iuus by the way, very little talk about this ...

    There were 6 deaths associated with infections in the RA phase III trial.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911947/


    Furthermore, there were 5 deaths associated with serious infections in the Lupus phase III trial.

    http://onlinelibrary.wiley.com/doi/10.1002/art.38037/full

    Both studies were halted due to these deaths using Ocrelizumab.

    On of the few that really highlights the risks with this Ocrelizumab is this professor Mark Freedman, who, for instance, did this statement at an interview at Ectrims 2015.

    https://www.youtube.com/watch?v=EzM1NbZ-7nU&feature=youtu.be


    My point:
    Given Ocrelizumabs history, I think it is about time to acknowledge that this agent comes with great risks, given its bad safety footprints both in previous studies in RA and Lupus, and now lastly in MS - referring then firstly to all these malignancies.

    Yes it appears to have a good efficacy towards halting relapses, but at what cost ? Roche wants of course to market this agent for a broad patient population to earn money. That is only natural wish for a business company.

    But to my opinion, use of Ocrelizumab could only be an option for patients who is willing to take the risks and have highly active MS-disease.

    And as professor Mark Freedman states in the above interview, what will happen in the long run when you suppress or deplete the B-cells so heavily as ocrelizumab doses ...?


    I just wish that we could have a more balanced discussion about risks and benefits. So far, to much of the debate is focused on the positive effects, but not so much is mentioned about Ocrelizumabs (OCREVUS) risks.

    Professor Mark Freedman is one of the few that stands up and air a more balanced view on risks and benefits with regard to this Ocrevus (Ocrelizumab).


    I hope you will have the courage to publish the above.

    Best wishes

    Liz

    ReplyDelete
  2. Please explain this post a little more. What is the main point ?

    "... the changes only occur at best in about 25% of pwMS" : What changes?

    ReplyDelete
  3. These cells only appear in about 9 of 40 peopleb so a minority.

    This was an excuse to start talking about B cells. I predict 2017 is going to be the year of the B cell as ocrevus gets a licence for RRMS, not sure what will happen with PPMS,. However it is important to realise that they are not amorphous and there are many subpopulations doing different things.

    ReplyDelete

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