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B cell numbers don't correlate with progression

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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.  

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