The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
27
06
2019
revised:
12
05
2020
accepted:
14
05
2020
pubmed:
18
5
2020
medline:
5
1
2021
entrez:
18
5
2020
Statut:
ppublish
Résumé
Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear. We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing-remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated. Forty-one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C-index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (β = 4.7*10 A specific CSF profile, mainly characterized by elevated levels of B-cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562-573.
Substances chimiques
Biomarkers
0
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
562-573Informations de copyright
© 2020 American Neurological Association.
Références
Kutzelnigg A, Lucchinetti CF, Stadelmann C, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005;128:2705-2712.
Lassmann H, Brück W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol 2007;17:210-218.
Magliozzi R, Howell OW, Reeves C, et al. A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol 2010;68:477-493.
Calabrese M, Magliozzi R, Ciccarelli O, et al. Exploring the origins of grey matter damage in multiple sclerosis. Nat Rev Neurosci 2015;16:147-158.
Scalfari A, Romualdi C, Nicholas RS, et al. The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis. Neurology 2018;90:e2107-e2118.
Calabrese M, Poretto V, Favaretto A, et al. Cortical lesion load associates with progression of disability in multiple sclerosis. Brain 2012;135:2952-2961.
Filippi M, Preziosa P, Rocca MA. MRI in multiple sclerosis: what is changing? Curr Opin Neurol 2018;31:386-395.
Magliozzi R, Howell O, Vora A, et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 2007;130:1089-1104.
Lucchinetti CF, Popescu BO, Bunyan R, et al. Inflammatory cortical demyelination in early multiple sclerosis. New Engl J Med 2011;365:2188-2197.
Pietroboni AM, Caprioli M, Carandini T, et al. CSF β-amyloid predicts prognosis in patients with multiple sclerosis. Mult Scler J 2018;25:1223-1231.
Sellebjerg F, Royen L, Soelberg Sørensen P, et al. Prognostic value of cerebrospinal fluid neurofilament light chain and chitinase-3-like-1 in newly diagnosed patients with multiple sclerosis. Mult Scler J 2018;25:1444-1451.
Magliozzi R, Howell OW, Nicholas R, et al. Inflammatory intrathecal profiles and cortical damage in multiple sclerosis. Ann Neurol 2018;83:739-755.
Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292-302.
Teunissen CE, Petzold A, Bennett JL, et al. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology 2009;73:1914-1922.
Opsahl JA, Vaudel M, Guldbrandsen A, et al. Label-free analysis of human cerebrospinal fluid addressing various normalization strategies revealing protein groups affected by multiple sclerosis. Proteomics 2016;16:1154-1165.
Geurts JJG, Roosendaal SD, Calabrese M, et al. Consensus recommendations for MS cortical lesion scoring using double inversion recovery MRI. Neurology 2011;76:418-424.
Fischl B. FreeSurfer. NeuroImage 2012;62:774-781.
Reuter M, Fischl B. Avoiding asymmetry-induced bias in longitudinal image processing. Neuroimage 2011;57:19-21.
Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227-231.
Havrdova E, Galetta S. Freedom from disease activity in multiple sclerosis. Neurology 2010;27:s3-s7.
Pitteri M, Romualdi C, Magliozzi R, et al. Cognitive impairment predicts disability progression and cortical thinning in MS: an 8-year study. Mult Scler J 2016;23:848-854.
Komori M, Blake A, Greenwood M, et al. Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis. Ann Neurol 2015;78:3-20.
Ferraro D, Galli V, Vitetta F, et al. Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: association with oligoclonal IgM bands and prediction of multiple sclerosis diagnosis. J Neuroimmunol 2015;283:64-69.
Ruggieri S, Pontecorvo S, Tortorella C, Gasperini C. Induction treatment strategy in multiple sclerosis: a review of past experiences and future perspectives. Mult Scler Demyelin Disord 2018;3:5.
Giovannoni G, Tomic D, Bright JR, Havrdová E. “ No evident disease activity ”: the use of combined assessments in the management of patients with multiple sclerosis. Mult Scler J 2017;23:1179-1187.
Gardner C, Magliozzi R, Durrenberger PF, et al. Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats. Brain 2013;136:3596-3608.
Lisak RP, Benjamins JA, Nedelkoska L, et al. Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro. J Neuroimmunol 2012;246:85-95.
Rainey-barger EK, Rumble JM, Lalor SJ, et al. Brain, behavior, and immunity the lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system. Brain Behav Immun 2011;25:922-931.
Esen N, Rainey-barger EK, Huber AK, et al. Type-I interferons suppress microglial production of the lymphoid chemokine, CXCL13. Glia 2014;62:1452-1462.
Stilund M, Gjelstrup MC, Petersen T, et al. Biomarkers of inflammation and axonal degeneration / damage in patients with newly diagnosed multiple sclerosis: contributions of the soluble CD163 CSF / serum ratio to a biomarker panel. PLoS One 2015;10:1-22.
Aloisi F, Pujol-borrell R. Lymphoid neogenesis in chronic inflammatory diseases. Nat Rev Immunol 2006;6:205-217.
Stilund M, Reuschlein A, Christensen T, et al. Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis. PLoS One 2014;9:1-8.
Lassmann H. Pathogenic mechanisms associated with different clinical courses of multiple sclerosis. Front Immunol 2018;9.1-14.
Mikol DD, Barkhof F, Chang P, et al. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer acetate in relapsing MS disease [REGARD] study): a multicentre, randomised, parallel, open-label trial. Lancet Neurol 2008;7:903-914.
Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. New Engl J Med 2012;367:1087-1097.