Sunday, 2 July 2017

To B or Not to T or to T and not to B

Expanding Role of T Cells in Human Autoimmune Diseases of the Central Nervous System. Pilli D, Zou A, Tea F, Dale RC, Brilot F.
Front Immunol. 2017;8:652. doi: 10.3389/fimmu.2017.00652.

It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease. Aberrant T cell responses, in particular, are key in driving autoimmunity and have been traditionally associated with multiple sclerosis. Yet, it is evident that there are other neurological diseases in which autoreactive T cells have an active role in pathogenesis. In this review, we report on the recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS) autoimmune disorders that are currently postulated to be primarily T cell driven. We also explore the autoreactive T cell response in a recently emerging group of syndromes characterized by autoantibodies against neuronal cell-surface proteins. Common methodology implemented in T cell biology is further considered as it is an important determinant in their detection and characterization. An improved understanding of the contribution of autoreactive T cells expands our knowledge of the autoimmune response in CNS disorders and can offer novel methods of therapeutic intervention.

Based on a review of the literature, it seems apparent that MS is a multifaceted autoimmune disease with potential contributions from Th17 cells and CD8+ T cells in demyelination. Although T cell dependency is well established, the quest for potential autoantibodies in MS is still going strong  Popularly studied autoantigens in this field include MOG and aquaporin 4 (AQP4), although extensive research into these targets reveal that they are not, in fact, associated with MS 

Jakimovski D, Weinstock-Guttman B, Ramanathan M, Kolb C, Hojnacki D, Minagar A, Zivadinov R.Ocrelizumab: A B-cell Depleting Therapy for Multiple Sclerosis. Expert Opin Biol Ther. 2017 Jun 29. doi: 10.1080/14712598.2017.1347632. [Epub ahead of print]

Multiple sclerosis (MS) is the most common neurological disease responsible for early disability in the young working population. In the last two decades, based on retrospective/prospective data, the use of disease-modifying therapies has been shown to slow the rate of disability progression and prolonged the time to conversion into secondary-progressive MS (SPMS). However, despite the availability of several approved therapies, disability progression cannot be halted significantly in all MS patients. Areas covered: This article reviews the immunopathology of the B-cells, and their role in pathogenesis of MS and their attractiveness as a potential therapeutic target in MS. The review focuses on the recently published ocrelizumab phase III trials in terms of its efficacy, safety, and tolerability as well as its future considerations. Expert opinion: B lymphocyte cell depletion therapy offers a compelling and promising new option for MS patients. Nonetheless, there is a need for heightened vigilance and awareness in detecting potential long-term consequences that currently remain unknown


Where would you pin your hopes, blocking T or B cells or Both? on

7 comments:

  1. Love your articles as always. As a person living with MS for 18 years, diagnosed 15 years, I know my share of disease modifying therapies (even have participated in a few clinical trials).

    I have been on and failed FIVE therapies. Four of those were T cell derivative therapies (Copaxone was the other therapy). I just recently started Ocrevus (ocrelizumab). This is my first B cell derivative therapy. I'm hoping this is the one. For me, it is worth the risk. As with any therapy or frankly any drug you take, you're taking a risk. Quality of life is what matters most right now.

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  2. Both would be the answer but neither will be a cure. B-cells and T-cells both talk and interact with on another so both are important in inflammation.

    The answer will be what is the antigen presenting cell that calls B and T-cells to action. This could be EBV controlled B-cells in follicles in the brain, hot microglia or A1 astrocytes or recent developments into misfolded myelin.

    The answer lies probably in the unfortunate MS patients who had massive relapses after removal of Tysabri and Gilenya. I think that you MD as an neuroimmunologist would come up with a far better assessment of the cause of the "field effect" than would a pathologist by assessing those tissue samples.

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    1. Totally agree with you Nissan. Perhaps they will continue the studies of Prof. Pender and Prof. Gavin will have some exact answers.

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  3. Re: "It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease." Oh really? Thanks

    Re: "The quest for auto antigens in MS, RE and ALS is ongoing...." Y---a--w---n......zzzzz

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  4. I think we need to focus on knocking out 100% of plasma cells and B cells within and without the CNS (not the stem cells).

    HSCT is the only thing that currently comes close to this. Ocrelizumab isn't bad but it doesn't get to B cells in the brain and doesn't touch plasma cells so the disease continues.



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