Sunday, 6 August 2017

B cell numbers don't correlate with progression

Wurth S, Kuenz B, Bsteh G, Ehling R, Di Pauli F, Hegen H, Auer M, Gredler V, Deisenhammer F, Reindl M, Berger T. Cerebrospinal fluid B cells and disease progression in multiple sclerosis - A longitudinal prospective study. PLoS One. 2017;12(8):e0182462

BACKGROUND:There is evidence that B cells play an important role in disease pathology of multiple sclerosis (MS). The aim of this prospective observational study was to determine the predictive value of cerebrospinal fluid (CSF) B cell subtypes in disease evolution of patients with MS.
MATERIALS AND METHODS:128 patients were included between 2004 and 2012. Median follow up time was 7.9 years (range 3.3-10.8 years). 10 patients were lost to follow-up. 32 clinically isolated syndrome- (CIS), 25 relapsing remitting MS- (RRMS), 2 secondary progressive MS- (SPMS) and 9 primary progressive MS- (PPMS) patients were included. The control group consisted of 40 patients with other neurological diseases (OND). CSF samples were analyzed for routine diagnostic parameters. B cell phenotypes were characterized by flow cytometry using CD19 and CD138 (Plasma cells) specific antibodies. Standardized baseline brain MRI was conducted at the time of diagnostic lumbar puncture. Main outcome variables were likelihood of progressive disease course, EDSS progression, conversion to clinical definite MS (CDMS) and relapse rate.
RESULTS: CSF mature B cells (CD19+, CD138-) were increased in bout-onset MS compared to PPMS (p<0.05) and OND (p<0.001), whereas plasma blasts (CD19+CD138+) were increased in bout-onset MS (p<0.001) and PPMS (p<0.05) compared to OND. CSF B cells did not predict a progressive disease course, EDSS progression, an increased relapse rate or the conversion to CDMS. Likelihood of progressive disease course (p<0.05) and EDSS (p<0.01) was predicted by higher age at baseline, whereas conversion to CDMS was predicted by a lower age at onset (p<0.01) and the presence of ≥9 MRI T2 lesions (p<0.05).

CONCLUSION: We detected significant differences in the CSF B cell subsets between different clinical MS subtypes and OND patients. CSF B cells were neither predictive for disease and EDSS progression nor conversion to CDMS after a CIS.

In this study they used CD138 as a marker for discrimination and this detects plasma blasts and plasma cells, which are the antibody producing cells and their precursors, the CD138- are not just the mature cells but they are also the memory cells. There were more common in active MS, but their number did not predict activity.

Is this a blow for the B cell brigade?. Maybe one would like to see an increase of B cells with increasing disease activity, but as we are not monitoring 24/7 and activity is more likely to be associated with MRI lesions. However the key cells are likely to be only a small subset of these populations and so we are looking for a needle in a haystack so this does not mean they are not part of the active component? But it means there is not a simple solution. The presence of B cells did not predict the development of progressive MS, but why would it if relapsing is simply part of the same of the spectrum.

However the vast majority, nearly 90% of the CSF cells were T cells and so the the number of B cells were small and they did not look at B memory cells. But would they have correlated with disease activity? We'll have to wait and see.  

5 comments:

  1. "MS is a B cell Disease and Memory B cells are the Target for therapy "
    Or not
    "This study identifies short-lived plasma blasts as the main effector B cell population involved in ongoing active inflammation in multiple sclerosis patients."
    https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awh486

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  2. In other words, we still don't have a clue.

    ReplyDelete
  3. This is strange, because Ocrelizumab, which is a B-cell depletor, is the only drug that has been able to do anything against Progressive Primary MS.
    Otherwise, the other drugs would also do something, which they can not. Tlavez are looking for the wrong B cell subpopulation, and probably plasma cells have a lot more to say...

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  4. "Given the stability of oligoclonal
    bands in multiple sclerosis patients who had undergone
    bone marrow transplantation, it is tempting to speculate
    that persistent memory B cells in the CNS are the source for the
    continuous local development of short-lived PB in the brain
    (Saiz et al., 2001). However, little overlap of B cell clonotypes in
    the CD138+ and CD19+ subset was observed in a recent study(Ritchie et al., 2001). Although this study did not differentiate
    between CD19+CD138+ and CD19+CD138– cells, the
    results would rather argue against continuous maturation of
    memory B cells to PB in the brain

    https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awh486

    ReplyDelete

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