OBJECTIVE: To determine whether B-cell presence in brainstem and white matter (WM) lesions is associated with poorer pathological and clinical characteristics in advanced MS autopsy cases. METHODS: Autopsy tissue of 140 MS and 24 control cases and biopsy tissue of 24 patients with MS were examined for CD20+ B cells and CD138+ plasma cells. The presence of these cells was compared with pathological and clinical characteristics. In corresponding CSF and plasma, immunoglobulin (Ig) G ratio and oligoclonal band (OCB) patterns were determined. In a clinical cohort of 73 patients, the presence of OCBs was determined during follow-up and compared to status at diagnosis. RESULTS: In 34% of active and 71% of mixed active/inactive lesions, B cells were absent, which correlated with less pronounced meningeal B-cell infiltration (p < 0.0001). The absence of B cells and plasma cells in brainstem and WM lesions was associated with a longer disease duration (p = 0.001), less frequent secondary progressive MS compared with relapsing and primary progressive MS (p < 0.0001 and p = 0.046, respectively), a lower proportion of mixed active/inactive lesions (p = 0.01), and less often perivascular T-cell clustering (p < 0.0001). Moreover, a lower CSF IgG ratio (p = 0.006) and more frequent absence of OCBs (p < 0.0001) were noted. In a clinical cohort, numbers of patients without OCBs in CSF were increased at follow-up (27.4%). CONCLUSIONS: The absence of B cells is associated with a favorable clinical and pathological profile. This finding may reflect extremes of a continuum of genetic or environmental constitution, but also a regression of WM humoral immunopathology in the natural course of advanced MS.

dx.doi.org/10.1212/NXI.0000000000000955, hdl.handle.net/1765/134807
Neurology(R) neuroimmunology & neuroinflammation

Fransen, N.L. (Nina L.), de Jong, B.A. (Brigit A.), Heß, K. (Katharina), Kuhlmann, T. (Tanja), Vincenten, M.C.J. (Maria C J), Hamann, J, … Smolders, J. (Joost). (2021). Absence of B Cells in Brainstem and White Matter Lesions Associates With Less Severe Disease and Absence of Oligoclonal Bands in MS. Neurology(R) neuroimmunology & neuroinflammation, 8(2). doi:10.1212/NXI.0000000000000955