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Inflammatory intrathecal profiles and cortical damage in multiple sclerosis
Author(s) -
Magliozzi Roberta,
Howell Owain W.,
Nicholas Richard,
Cruciani Carolina,
Castellaro Marco,
Romualdi Chiara,
Rossi Stefania,
Pitteri Marco,
Benedetti Maria Donata,
Gajofatto Alberto,
Pizzini Francesca B.,
Montemezzi Stefania,
Rasia Sarah,
Capra Ruggero,
Bertoldo Alessandra,
Facchiano Francesco,
Monaco Salvatore,
Reynolds Richard,
Calabrese Massimiliano
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25197
Subject(s) - meninges , medicine , multiple sclerosis , cerebrospinal fluid , pathology , proinflammatory cytokine , inflammation , chemokine , neuroinflammation , cxcl10 , immunology , disease
Objective Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course? Methods To identify possible biomarkers linking meningeal inflammation, GM damage, and disease severity, gene and protein expression were analyzed in meninges and cerebrospinal fluid (CSF) from 27 postmortem secondary progressive MS and 14 control cases. Combined cytokine/chemokine CSF profiling and 3T magnetic resonance imaging (MRI) were performed at diagnosis in 2 independent cohorts of MS patients (35 and 38 subjects) and in 26 non‐MS patients. Results Increased expression of proinflammatory cytokines (IFNγ, TNF, IL2, and IL22) and molecules related to sustained B‐cell activity and lymphoid‐neogenesis (CXCL13, CXCL10, LTα, IL6, and IL10) was detected in the meninges and CSF of postmortem MS cases with high levels of meningeal inflammation and GM demyelination. Similar proinflammatory patterns, including increased levels of CXCL13, TNF, IFNγ, CXCL12, IL6, IL8, and IL10, together with high levels of BAFF, APRIL, LIGHT, TWEAK, sTNFR1, sCD163, MMP2, and pentraxin III, were detected in the CSF of MS patients with higher levels of GM damage at diagnosis. Interpretation A common pattern of intrathecal (meninges and CSF) inflammatory profile strongly correlates with increased cortical pathology, both at the time of diagnosis and at death. These results suggest a role for detailed CSF analysis combined with MRI as a prognostic marker for more aggressive MS. Ann Neurol 2018 Ann Neurol 2018;83:739–755