Oligoclonal bands…here to stay

O

J Neuroimmunol. 2019 May 16;333:576966. doi: 10.1016/j.jneuroim.2019.576966. [Epub ahead of print]

Persistence of intrathecal oligoclonal B cells and IgG in multiple sclerosis.

Tomescu-Baciu AJohansen JNHolmøy TGreiff VStensland Mde Souza GAVartdal FLossius A.

Abstract

In multiple sclerosis (MS), B cells are trafficking across the blood-brain barrier, but it is not known how this relates to the synthesis of oligoclonal IgG. We used quantitative mass spectrometry of oligoclonal bands and high-throughput sequencing of immunoglobulin heavy-chain variable transcripts to study the longitudinal B cell response in the cerebrospinal fluid (CSF) and blood of two MS patients. Twenty of 22 (91%) and 25 of 28 (89%) of oligoclonal band peptides persisted in samples collected 18 months apart, in spite of a dynamic exchange across the blood-CSF barrier of B lineage cells connecting to oligoclonal IgG.

This post is for Dr. Love who was asking about persistence of oligoclonal bands in MS. Once B cell clones arrive in the CNS and produce oligoclonal bands, they seem to persist. Even despite treatment with natalizumab. Therefore we need agents that can get in the brain to do their stuff. It seems obvious, doesn’t it. It’s surprising that they don’t always make agents to get in the brain. Can we get rid of them?. ProfG and NDG aim to find out

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MouseDoctor

11 comments

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  • We’ll, I would say there is a hint that we actually can do it (Rejdak’s Cladribine observational study)…

    I’m eagerly waiting for your (Barts) results, too!

  • ” Once B cell clones arrive in the CNS and produce oligoclonal bands, they seem to persist.”

    “Therefore we need agents that can get in the brain to do their stuff.”

    Other have allready try and succeeded

    The present study describes the histopathological changes
    found in autopsies of multiple sclerosis patients who had
    received ASCT. Histopathological and immunocytochemical
    examinations revealed a marked suppression of inflammatory
    activity with very few T cells and no B cells or plasma
    cells within the lesions, either parenchymally or perivascularly.
    However, we found signs of ongoing active demyelination
    as well as evidence for recent acute axonal damage
    in areas of macrophage/microglial activation.

    “Surprisingly, we found no B cells, plasma cells or
    lymphoid follicle-like structures in our cases,”

    Thus, the pathogenic role of plasma cells or antibodymediated
    damage remains uncertain

    This is good stuff for your bortezomib trial

    So ,no b cell ,no t cell ,no plasma cells, no antibodies ,no lymphoid follicle-like structures

    And still progression

    For your consideration

    Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis

    https://academic.oup.com/brain/article/130/5/1254/282210

    Obrigado
    Luis

    • Remember these people died and therefore their treatment with HSCT was not sufficiently effective and they had CD8 T cell lesions and they didn’t find B cells or plasma cells in lesions…however oe has progression without these in the places looked…think glia

    • On the other hand, Dr Fedorenko from Ru who has been treating with HSCT many MS patients, believes that oligo. bands can persist after HSCT treatment and do not indicate disease activity. That was his opinion expressed on an email to a patient, but it would be nice if we could see real life data.

      • Recovery from and consequences of severe iatrogenic
        lymphopenia (induced to treat autoimmune diseases)

        Surprisingly, antibody levels did not drop substantially, in spite of the severe CD4 T and B
        lymphopenia during the first several months posttransplant. Consistent with that, oligoclonal
        immunoglobulins in the cerebrospinal fluid of most multiple sclerosis patients treated with
        autologous transplantation did not disappear [3,37,38]. As the half life of IgM and IgA is only
        ~5 days and that of IgG only ~23 days [39], the antibodies detected in the sera of our patients
        were continuously produced, presumably by plasma cells generated pretransplant. Plasma cells
        are radiation-resistant and long-lived [40–42]. The persistent antibody production does not
        appear to require posttransplant exposure of patients to the cognate antigens. Tetanus IgG levels
        in the first posttransplant year remained stable, even though the patients were not vaccinated
        in the first year and natural exposure to tetanus toxin in developed countries is extremely
        unlikely [43]. However, it is unclear whether this applies to other autologous transplant settings.
        In three studies presenting tetanus antibody levels after autologous transplantation for
        malignancies, the levels appeared to drop between pretransplant and 1 year posttransplant
        [44–46].
        From the infectious disease point of view, the persistent production of antibodies by plasma
        cells generated before the autologous transplantation may be beneficial, as most frequent
        pathogens are likely encountered pretransplant. Unfortunately, from the point of view of
        autoimmune diseases caused by autoantibodies like pemphigus (anti-desmoglein) or Lambert–
        Eaton myasthenic syndrome (anti-voltage gated calcium channel), the persistent production of
        autoantibodies may be deleterious. This may not apply to systemic sclerosis or multiple
        sclerosis in which the role of autoantibodies is uncertain

        doi:10.1016/j.clim.2004.07.006

        • Ongoing demyelination and neurodegeneration in the absence of lymphocyte infiltrates has also been observed ;ong after post HSCT (Brain pathology of a patient 7years after autologous hematopoietic stem cell transplantation for multiple sclerosis (Wundes A, Bowen JD, Kraft GH, Maravilla KR, McLaughlin B, von Geldern G, Georges G, Nash RA, Lu JQ.J Neurol Sci. 2017 Feb 15;373:339-341. doi: 10.1016/j.jns.2017.01.016. Epub 2017 Jan 7. and Continued disease activity in a patient with multiple sclerosis after allogeneic hematopoietic cell transplantation. Lu JQ, Storek J, Metz L, Yong VW, Stevens AM, Nash RA, Joseph JT. Arch Neurol. 2009 Jan;66(1):116-20.). In addition, oligoclonal bands in CSF may weaken but generally don’t disappear after AHSCT. To me it seems AHSCT is just the biggest hammer to knock down the immune system, which is very effective in early to mid stage MS, but not in later stages. The ongoing neurodegeneration in later stages may be accelerated aging or related to the virtual hypoxia that Lassmann describes in his publication. Still eliminating lymphocytes from the CNS and meninges is a worthy goal, if it can be accomplished without too much toxicity, and it should probably be done before severe disability develops.

  • So, if B cell clones arrive in the CNS and produce oligoclonal bands, does that mean that pwMS (PPMS) like myself that lack oligoclonal bands done have B cells in the CNS?

  • So the same applies to other patient groups who have OCB+ (stroke etc)?
    Or if you prove the hype (in our case B cells) you are cool?

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