Although meningeal B-cell infiltrates characterize progressive disease and cortical pathology in multiple sclerosis (MS), active and mixed active/inactive white matter lesions with lymphocytic infiltrates are also observed in advanced MS autopsy cases.
We assessed the association between B-cell presence in brainstem and white matter lesions with pathological and clinical characteristics in MS autopsy cases.
Autopsy tissue of 140 MS and 24 control cases, as well as diagnostic biopsies of 24 MS patients were examined for CD20+ B cells and CD138+ plasma cells. Presence of these cells was compared to pathological and clinical characteristics. In corresponding cerebrospinal fluid (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 at diagnosis and during follow-up.
B cells were mostly found in the perivascular space and the meninges, but were also enriched in active and mixed active/inactive white matter MS lesions. In 34% of active and 71% of mixed active/inactive lesions, B cells were absent, which correlated with less pronounced meningeal B-cell infiltration. In an extreme of outcomes-analysis, donors without B cells or plasma cells at all locations analyzed, displayed a longer disease duration, less frequent secondary progressive MS, and a lower proportion of mixed active/inactive lesions when compared to donors with B cells and/or plasma cells at all locations. Moreover, a lower CSF IgG ratio and more frequent absence of OCBs were noted. In a clinical cohort, numbers of patients without OCBs in CSF were increased at follow-up.
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 white matter humoral immunopathology in the natural course of advanced MS.