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03.12.2018 | Original Communication

A controlled inflammation and a regulatory immune system are associated with more favorable prognosis of progressive multifocal leukoencephalopathy

verfasst von: Nobuo Sanjo, Yurie Nose, Yukiko Shishido-Hara, Saneyuki Mizutani, Yoshiki Sekijima, Hitoshi Aizawa, Toru Tanizawa, Takanori Yokota

Erschienen in: Journal of Neurology | Ausgabe 2/2019

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Abstract

Objective

In the present study, we analyzed the inflammatory profiles of brain tissues obtained from patients with progressive multifocal leukoencephalopathy (PML) due to John Cunningham (JC) virus infection to identify potential prognostic factors.

Methods

The study included seven patients (two men, five women) who had been pathologically diagnosed with PML, and all of whom were HIV negative. Fixed brain samples were analyzed via hematoxylin and eosin (HE) staining and Klüver–Barrera (KB) staining. We then performed immunohistochemistry (IHC) specific to JC virus capsid proteins (VP1 and VP2/3) and lymphocyte surface markers (CD4, CD8, CD138, and PD-1).

Results

The mean age at onset was 53.4, while the mean duration until biopsy/autopsy was 4.7 months. Four patients were included in the good prognosis (GP) group, while three were included in the poor prognosis (PP) group. Pathological analysis revealed a significantly larger number of CD4-positive T-cell infiltrations (P = .029) in the GP group, along with a preserved CD4:CD8 ratio. Larger numbers of CD138-positive plasma cells were also observed in the GP group (P = .029) than in the PP group. Linear regression analyses revealed a significant association between the numbers of CD138-positive plasma cells and PD-1-positive cells (R² = 0.80).

Conclusions

Viral loads in the cerebrospinal fluid, a controlled inflammatory response mediated by CD4- and CD8-positive T cells, and plasma cells are associated with PML prognosis. Our findings further indicate that regulatory plasma cells may regulate inflammatory T-cell activity via a PD-1/PD-L1 immuno-checkpoint pathway, thereby protecting the uninfected brain from excessive immune-mediated damage during an active JC virus infection.

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Titel: A controlled inflammation and a regulatory immune system are associated with more favorable prognosis of progressive multifocal leukoencephalopathy
verfasst von: Nobuo Sanjo
Yurie Nose
Yukiko Shishido-Hara
Saneyuki Mizutani
Yoshiki Sekijima
Hitoshi Aizawa
Toru Tanizawa
Takanori Yokota
Publikationsdatum: 03.12.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 2/2019
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-018-9140-0

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Methods

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Conclusions

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