B Cell Subsets in the Cerebrospinal Fluid of Multiple Sclerosis Patients (P4.134)

OBJECTIVE: To determine differences in B cell profiles in multiple sclerosis (MS) subtypes. BACKGROUND: It is established that B cell related abnormalities are seen in the cerebrospinal fluid (CSF) of 90% of MS patients. It is not known whether the clinical subtypes of MS correlate with specific B cell profiles. We studied the CSF profile of mature B cells, plasmablasts, and plasma cells and correlated these findings with the clinical presentations of MS patients. DESIGN/METHODS: This study was IRB approved and informed consent was obtained. CSF from 20 relapsing remitting (RRMS), 33 secondary progressive (SPMS), and 29 primary progressive multiple sclerosis (PPMS) patients were obtained by lumbar puncture. CSF was centrifuged and the pelleted cells re-suspended in PBS. Total mouse IgG was added to saturate Fc receptors and prevent non-specific antibody binding. Anti-Human CD19-APC and anti-human CD138-FITC were added to stain cells of the B cell lineage. Stained cells were separated into three subsets; CD19+ CD138- B cells, CD19+ CD138+ plasmablasts, and CD19- CD138+ plasma cells. Cytometer gates were established using peripheral blood mononuclear cells and previous positively stained CSF cells. RESULTS: Comparing the percentage of each B cell subset to the total B cell lineage, Kruskal-Wallis test showed a significant difference between the 3 subtypes of MS in plasma cells (p=0.0266.) There was a significant decrease in plasmablasts in SPMS vs. PPMS (p=0.0438) and a highly significant decrease in plasma cells in PPMS vs. SPMS (p=0.0057) as determined by Mann-Whitney T-test. Analysis of a subgroup of patients not on therapy (SPMS n=7, PPMS n=8) also showed a significant decrease in plasmablasts in SPMS vs PPMS (p=0.0228) and lower plasma cells in PPMS vs. SPMS (although not significant possibly due to small sample size.) CONCLUSIONS: Our results show that there are no differences between mature B cells in MS subtypes. However SPMS patients have significantly increased plasma cells and PPMS patients have significantly increased plasmablasts in the CSF.