Pubblicazioni

Autori:

Magliozzi, R; Hametner, S; Mastantuono, M; Mensi, A; Karimian, M; Griffiths, L; Watkins, L M; Poli, A; Berti, G M; Barusolo, E; Bellini, B; Rossi, S; Gveric, D; Stratton, J A; Akassoglou, K; Magon, S; Nicholas, R; Reynolds, R; Howell, O W; Monaco, S

Titolo:

Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis

Anno:

2024

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Formato:

Elettronico

Referee:

Sì

Nome rivista:

Brain Pathology

ISSN Rivista:

1015-6305

N° Volume:

First published online: 01 Dicember 2024

Intervallo pagine:

1-20

Parole chiave:

choroid plexus; gradient; inflammation; multiple sclerosis

Breve descrizione dei contenuti:

Among the intrathecal inflammatory niches where compartmentalized inflammation persists and plays a pivotal role in progressive multiple sclerosis (MS), choroid plexus (CP) has recently received renewed attention. To better characterize the neuropathological/molecular correlates of CP in progressive MS and its potential link with other brain inflammatory compartments, such as perivascular spaces and leptomeninges, the levels, composition and phenotype of CP immune infiltration in lateral ventricles of the hippocampus were examined in 40 post-mortem pathologically confirmed MS and 10 healthy donors, using immunochemistry/immunofluorescence and in-situ sequencing. Significant inflammation was detected in the CP of 21 out of the 40 MS cases (52%). The degree of CP inflammation was found correlated with: number of CP macrophages (R: 0.878, p = 1.012 x 10-13) and high frequency of innate immune cells expressing the markers MHC-class II, CD163, CD209, CD11c, TREM2 and TSPO; perivascular inflammation (R: 0.509, p = 7.921 x 10-4), and less with meningeal inflammation (R: 0.365, p = 0.021); number of active lesions (R: 0.51, p: 3.524 x 10-5). However, it did not significantly correlate with any clinical/demographic characteristics of the examined population. In-situ sequencing analysis of gene expression in the CP of 3 representative MS cases and 3 controls revealed regulation of inflammatory pathways mainly related to 'type 2 immune response', 'defense to infections', 'antigen processing/presentation'. Analysis of 78 inflammatory molecules in paired post-mortem CSF, the levels of fibrinogen (R: 0.640, p = 8.752 x 10-6), PDGF-bb (R: 0.470, p = 0.002), CXCL13 (R: 0.428, p = 0.006) and IL15 (R: 0.327, p = 0.040) were correlated with extent of CP inflammation. Elevated fibrinogen and complement deposition were found in CP and in underlying subependymal periventricular areas, according to "surface-in" gradient associated with concomitant prominent microglia activation. CP inflammation, predominantly characterized by innate immunity, represents another key determinant of intrathecal, compartmentalised inflammation persisting in progressive MS, which may be possibly activated by fibrinogen and influence periventricular pathology, even without substantial association with clinical features.

Pagina Web:

https://doi.org/10.1111/bpa.13322

Id prodotto:

142891

Handle IRIS:

11562/1146232

ultima modifica:

6 febbraio 2025

Citazione bibliografica:

Magliozzi, R; Hametner, S; Mastantuono, M; Mensi, A; Karimian, M; Griffiths, L; Watkins, L M; Poli, A; Berti, G M; Barusolo, E; Bellini, B; Rossi, S; Gveric, D; Stratton, J A; Akassoglou, K; Magon, S; Nicholas, R; Reynolds, R; Howell, O W; Monaco, S, Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis «Brain Pathology» , vol. First published online: 01 Dicember 2024 , 2024 , pp. 1-20

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