R.M. and O.W.H. contributed equally to this work.
A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis
Article first published online: 25 OCT 2010
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 68, Issue 4, pages 477–493, October 2010
How to Cite
Magliozzi, R., Howell, O. W., Reeves, C., Roncaroli, F., Nicholas, R., Serafini, B., Aloisi, F. and Reynolds, R. (2010), A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol., 68: 477–493. doi: 10.1002/ana.22230
- Issue published online: 25 OCT 2010
- Article first published online: 25 OCT 2010
- Manuscript Accepted: 13 AUG 2010
- Manuscript Revised: 30 JUL 2010
- Manuscript Received: 5 OCT 2009
Additional Supporting Information can be found in the online version of this article.
|ANA_22230_sm_suppfig1.tif||25515K||Supporting Figure 1. Characterization of meningeal B-cell follicle-like structures. B cell follicle positive (F+) MS cases were defined by the presence of one or more B cell aggregates containing follicular dendritic cells, proliferating B cells, plasma cells and T cells. Initial analysis of cryosections from 11-12 snap or fixed frozen tissue blocks (4cm3; containing neocortex and preserved meninges) from frontal, temporal, parietal and occipital lobes was performed. In the first instance, haematoxylin/eosin histological assessment of meningeal and perivascular cellular infiltrates identified lymphocytic aggregates within the meninges or perivascular spaces (A). Adjacent sections from those revealing lymphocytic aggregates by histology were stained for CD20+ B cells, and dense aggregates of CD20+ B cells were analysed with a panel of markers to determine their status as ectopic lymphoid-like tissue. B cell follicle-like structures were characterised by the presence of numerous CD20+ B lymphocytes (B), CD4+ and CD8+ lymphocytes (C and D), CD35+ (E,F) and CXCL13+ (G) stromal cells/follicular dendritic cells, numerous Ig+ (Ig-G, -A, -M) plasmablasts and plasma cells (H) and proliferating Ki67+CD20+ B lymphocytes (I). The incidence of B cell follicles per case is listed in table 1. A number of F+ SPMS cases, such as MS092, contained numerous B cell follicle-like structures whilst others (e.g MS085, MS109) contained only two B cell follicle-like structures in eleven tissue blocks analysed. Follicle negative cases were confirmed by the independent assessment of a further 12-16 paraffin embedded tissue blocks taken as part of the standard neuropathological assessment performed by F.R. No significant lymphocytic aggregates were noted in the 17 follicle negative cases used in this study. A minimum of 24 tissue blocks were analysed to confirm a case as being negative for B-cell follicle-like structures. Scale bars= 50μm (A-D), 40μm (E), 20μm (G-I), 10μm (F)|
|ANA_22230_sm_suppfig2.tif||25512K||Supporting Figure 2|
|ANA_22230_sm_suppfig3.tif||25511K||Supporting Figure 3|
|ANA_22230_sm_supptab1.doc||34K||Supporting Table 1|
|ANA_22230_sm_supptab2.doc||51K||Supporting Table 2|
|ANA_22230_sm_supptab3.doc||30K||Supporting Table 3|
Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.