The success of B-cell-depleting therapies tells us that B cells play an important role in driving MS. We don't really understand how - they may be producing antibodies targeted against 'self', they may be recruiting other immune players like T lymphocytes and monocytes, or they may be doing both.
There are many different types of B cell, each of which has a different set of roles in the immune system.
So a sensible question to ask is whether the numbers and types of B cell present in the CSF - the spinal fluid - can predict the course of the disease.
A new study asked this question by looking at 128 pwMS and 40 people with other neurological disorders as their control group. They took samples of CSF - spinal fluid - and analysed the different subsets of B cells present. They then correlated this information with clinical details such as disease course and MRI findings.
The numbers of mature B cells and plasmablasts (the precursors to long-lived antibody-secreting plasma cells) were raised in the group of people with bout-onset forms of MS (CIS, RRMS, SPMS) compared to PPMS and the control group. There was no difference in T cell numbers between the groups.
CSF lymphocyte counts were not predictive of disability progression, conversion from CIS to RRMS.
This is very interesting. It implies that the CSF B cell profile is 'diagnostic' but not 'prognostic'. CSF B cells may be involved in driving relapses or may be a consequence of a 'leaky' blood-brain barrier in relapse-onset disease. What is odd and intriguing is that CSF B cells were not raised in PPMS. Given the success of ocrelizumab - a B cell depleter - in PPMS it is a bit counter-intuitive that this group did not show any evidence of having high CSF B counts. This may be because only two types of B cells, mature and plasmablasts, were examined here. In fact, the number of B lymphocytes in the CSF of the pwPPMS was slightly raised (although not statistically significant) compared to the control group. Given that the control group were also people with neurologic disorders, many of whom would be expected to have a degree of CNS inflammation, we may be missing a genuine difference here. Further studies are needed to examine the CSF of pwPPMS to determine whether there is a selective increase in specific B cell populations, such as the memory B's.
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 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.
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).
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.
Labels: B Cells, prognosis