Demographic, clinical and CSF data of analyzed patients.

<p><b>1</b> data are shown as median (range), p-value: groups were compared using <b>2</b> Qui-Square test or <b>3</b> Kruskal-Wallis test and Dunn's multiple comparison post-hoc test, # statistically significant different from OND control group.</p><p>Abbreviations: n = number of patients, y = years, EDSS = expanded disability status score, acute relapse = number of patients with an acute relapse, MRI Gd+ lesions = presence of gadolinium-enhancing lesions on T1-weighted MRI (neg = negative, pos = positive), ≥9 T2 MRI lesions = ≥9 lesions on T2-weighted MRI, OCB = oligoclonal bands, Q-Alb = albumin quotient, MMP = matrix metalloproteinase, ratio = CSF∶serum ratio, ns = statistically not significant.</p

CSF B cell subsets.

<p>(A) Dot plots of CSF leucocytes according to their CD45-PerCP versus side scatter properties (left panel) and forward versus side scatter properties (right panel). Region 1 (R1, left panel) was used for acquisition of a minimum number of 1000 events and region 2 (R2, right panel) was used for analysis. CSF analysis of representative patients with a CIS (B), RRMS (C), CPMS (D) and OND (E) for the presence of CD3+ T cells and CD19+ B cells (left panel), and CD19+CD138− mature B cells, CD19+CD138+ plasma blasts and CD19−CD138+ plasma cells (right panel). The numbers represent the relative percentages of these cell populations.</p

Correlation of CSF B cells with other inflammatory parameters.

<p><b>1</b> data are shown as median (range), p-value: groups were compared using <b>2</b> Mann-Whitney U test or <b>3</b> Spearmans nonparametric correlations.</p><p>Abbreviations: MRI Gd+ lesions = presence of gadolinium-enhancing lesions on T1-weighted MRI (neg = negative, pos = positive), MRI T2 lesions = number of lesions on T2-weighted MRI, Q-Alb = albumin quotient, OCB = oligoclonal bands, MMP = matrix metalloproteinase, R = Spearman's correlation coefficient, ns = statistically not significant.</p

Percentages of CD3+ T cells (A), CD19+CD138− mature B cells (B) and CD19+CD138+ plasma blasts (C) in the CSF of patients with a CIS, RRMS, CPMS and OND.

<p>Individual data points are shown as circles and horizontal bars indicate means. Data were compared using the Kruskal-Wallis test and Dunn's multiple comparison post-hoc test and overall p-values are shown in each figure. # = significant differences to the OND group.</p

Cerebrospinal fluid B cells and disease progression in multiple sclerosis - A longitudinal prospective study

<div><p>Background</p><p>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.</p><p>Materials and methods</p><p>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.</p><p>Results</p><p>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).</p><p>Conclusion</p><p>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.</p></div

CSF lymphocyte populations and clinical parameters of CIS patients with and without conversion to RRMS.

<p>CSF lymphocyte populations and clinical parameters of CIS patients with and without conversion to RRMS.</p

Differences in lymphocyte populations and clinical parameters between MS patients with and without EDSS progression (delta EDSS 1 for BL EDSS 0–5.5, delta EDSS 0.5 for BL EDSS 6–10).

<p>Differences in lymphocyte populations and clinical parameters between MS patients with and without EDSS progression (delta EDSS 1 for BL EDSS 0–5.5, delta EDSS 0.5 for BL EDSS 6–10).</p

CSF lymphocyte populations in bout-onset MS, PPMS and OND.

<p>CSF lymphocyte populations in bout-onset MS, PPMS and OND.</p

Differences in CSF lymphocyte populations and clinical parameters between MS patients with (SPMS and PPMS) and without disease progression (CIS, RRMS).

<p>Differences in CSF lymphocyte populations and clinical parameters between MS patients with (SPMS and PPMS) and without disease progression (CIS, RRMS).</p

Differences in CSF lymphocyte populations and clinical parameters between bout-onset MS (CIS, RRMS and SPMS) versus PPMS.

<p>Differences in CSF lymphocyte populations and clinical parameters between bout-onset MS (CIS, RRMS and SPMS) versus PPMS.</p