PT  - JOURNAL ARTICLE
AU  - Nina L. Fransen
AU  - Brigit A. de Jong
AU  - Katharina Heß
AU  - Tanja Kuhlmann
AU  - Maria C.J. Vincenten
AU  - Jörg Hamann
AU  - Inge Huitinga
AU  - Joost Smolders
TI  - Absence of B Cells in Brainstem and White Matter Lesions Associates With Less Severe Disease and Absence of Oligoclonal Bands in MS
AID  - 10.1212/NXI.0000000000000955
DP  - 2021 Mar 04
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e955
VI  - 8
IP  - 2
4099  - http://nn.neurology.org/content/8/2/e955.short
4100  - http://nn.neurology.org/content/8/2/e955.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 Mar 04; 8
AB  - 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.GM=gray matter; IgG=immunoglobulin G; MO=medulla oblongata; MOG=myelin oligodendrocyte glycoprotein; NBB=Netherlands Brain Bank; OCB=oligoclonal band; PP=primary progressive; RR=relapsing-remitting; SP=secondary progressive; TRM=tissue-resident memory T (cells); WM=white matter