Cerebrospinal Fluid IgM Levels in Association With Inflammatory Pathways in Multiple Sclerosis Patients.
B cell
CSF
immunoglobulin M
lesion activity
multiple sclerosis
Journal
Frontiers in cellular neuroscience
ISSN: 1662-5102
Titre abrégé: Front Cell Neurosci
Pays: Switzerland
ID NLM: 101477935
Informations de publication
Date de publication:
2020
2020
Historique:
received:
05
06
2020
accepted:
22
09
2020
entrez:
16
11
2020
pubmed:
17
11
2020
medline:
17
11
2020
Statut:
epublish
Résumé
Intrathecal immunoglobulin M (IgM) synthesis has been demonstrated in the early disease stages of multiple sclerosis (MS) as a predictor factor of a worsening disease course. Similarly, increased cerebrospinal fluid (CSF) molecules related to B-cell intrathecal activity have been associated with a more severe MS progression. However, whether CSF levels of IgM are linked to specific inflammatory and clinical profile in MS patients at the time of diagnosis remains to be elucidated. Using customized Bio-Plex assay, the protein levels of IgG, IgA, IgM, and of 34 other inflammatory molecules, related to B-cell, T-cell, and monocyte/macrophage activity, were analyzed in the CSF of 103 newly diagnosed relapsing-remitting MS patients and 36 patients with other neurological disorders. CSF IgM levels were also correlated with clinical and neuroradiological measures [advanced 3-T magnetic resonance imaging (MRI) parameters], at diagnosis and after 2 years of follow-up. A 45.6% increase in CSF IgM levels was found in MS patients compared to controls ( IgMs are the immunoglobulins mostly expressed in the CSF of naive MS patients compared to other neurological conditions at the time of diagnosis. The association between increased CSF IgM levels and molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1, and CHI3L1) suggests possible correlation between humoral and innate intrathecal immunity in early disease stage. Furthermore, the association of IgM levels with WMLs and MS clinical and MRI activity after 2 years supports the idea of key role of IgM in the disease course.
Sections du résumé
BACKGROUND
BACKGROUND
Intrathecal immunoglobulin M (IgM) synthesis has been demonstrated in the early disease stages of multiple sclerosis (MS) as a predictor factor of a worsening disease course. Similarly, increased cerebrospinal fluid (CSF) molecules related to B-cell intrathecal activity have been associated with a more severe MS progression. However, whether CSF levels of IgM are linked to specific inflammatory and clinical profile in MS patients at the time of diagnosis remains to be elucidated.
METHODS
METHODS
Using customized Bio-Plex assay, the protein levels of IgG, IgA, IgM, and of 34 other inflammatory molecules, related to B-cell, T-cell, and monocyte/macrophage activity, were analyzed in the CSF of 103 newly diagnosed relapsing-remitting MS patients and 36 patients with other neurological disorders. CSF IgM levels were also correlated with clinical and neuroradiological measures [advanced 3-T magnetic resonance imaging (MRI) parameters], at diagnosis and after 2 years of follow-up.
RESULTS
RESULTS
A 45.6% increase in CSF IgM levels was found in MS patients compared to controls (
CONCLUSION
CONCLUSIONS
IgMs are the immunoglobulins mostly expressed in the CSF of naive MS patients compared to other neurological conditions at the time of diagnosis. The association between increased CSF IgM levels and molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1, and CHI3L1) suggests possible correlation between humoral and innate intrathecal immunity in early disease stage. Furthermore, the association of IgM levels with WMLs and MS clinical and MRI activity after 2 years supports the idea of key role of IgM in the disease course.
Identifiants
pubmed: 33192314
doi: 10.3389/fncel.2020.569827
pmc: PMC7596330
doi:
Types de publication
Journal Article
Langues
eng
Pagination
569827Informations de copyright
Copyright © 2020 Magliozzi, Mazziotti, Montibeller, Pisani, Marastoni, Tamanti, Rossi, Crescenzo and Calabrese.
Références
Ann Neurol. 2010 Sep;68(3):369-83
pubmed: 20641064
Mult Scler. 2012 Feb;18(2):174-80
pubmed: 21868488
Brain. 2013 Dec;136(Pt 12):3596-608
pubmed: 24176976
Ann Neurol. 2010 Oct;68(4):477-93
pubmed: 20976767
Arch Neurol. 1971 Oct;25(4):326-44
pubmed: 4999855
PLoS One. 2010 Aug 05;5(8):e11986
pubmed: 20700489
J Immunol. 2002 Jan 1;168(1):458-65
pubmed: 11751993
Mult Scler Relat Disord. 2015 Jul;4(4):329-33
pubmed: 26195051
Brain. 2010 Apr;133(Pt 4):1082-93
pubmed: 20237129
Neurology. 2011 Feb 1;76(5):418-24
pubmed: 21209373
J Neuroimmunol. 2006 Nov;180(1-2):33-9
pubmed: 16952404
Neurology. 2008 Mar 25;70(13 Pt 2):1079-83
pubmed: 17881717
Mult Scler. 2012 May;18(5):587-91
pubmed: 21965422
J Neurol. 2000 Aug;247(8):609-15
pubmed: 11041328
Neurology. 2009 Dec 1;73(22):1914-22
pubmed: 19949037
J Exp Med. 1986 Jan 1;163(1):41-53
pubmed: 3941297
Ann Neurol. 2020 May 17;:
pubmed: 32418239
Neurotherapeutics. 2007 Oct;4(4):590-601
pubmed: 17920540
Inflamm Allergy Drug Targets. 2009 Mar;8(1):40-52
pubmed: 19275692
Ann Neurol. 2009 Jun;65(6):639-49
pubmed: 19557869
Neurology. 2002 Mar 12;58(5):824-6
pubmed: 11889253
Cytokine. 2015 Jul;74(1):27-34
pubmed: 25481648
Brain. 2007 Apr;130(Pt 4):1089-104
pubmed: 17438020
J Neurol Sci. 2008 Nov 15;274(1-2):45-7
pubmed: 18495163
J Neurosci Res. 2002 Aug 1;69(3):418-26
pubmed: 12125082
Lancet Neurol. 2018 Feb;17(2):162-173
pubmed: 29275977
Mult Scler. 2011 Mar;17(3):335-43
pubmed: 21135023
Acta Neurol Scand. 1986 Dec;74(6):417-24
pubmed: 3103370
Adv Exp Med Biol. 1978;100:529-43
pubmed: 696479
Mult Scler. 2008 Mar;14(2):183-7
pubmed: 17942517
Neurology. 2019 Oct 8;93(15):e1439-e1451
pubmed: 31501228
Neurology. 1983 Nov;33(11):1444-52
pubmed: 6685237
Mol Immunol. 2000 Dec;37(18):1141-9
pubmed: 11451419
Ann Clin Transl Neurol. 2019 Nov;6(11):2150-2163
pubmed: 31675181
Front Neurol. 2019 Nov 22;10:1232
pubmed: 31824409
J Neuroinflammation. 2019 Dec 23;16(1):272
pubmed: 31870389
Sci Transl Med. 2015 Oct 21;7(310):310ra166
pubmed: 26491076
Neurology. 1983 Oct;33(10):1305-10
pubmed: 6604241
Brain. 2011 Sep;134(Pt 9):2755-71
pubmed: 21840891
Brain. 2014 Oct;137(Pt 10):2703-14
pubmed: 25060097
Mult Scler. 2011 Mar;17(3):327-34
pubmed: 21123302
Ann Neurol. 2003 Feb;53(2):222-6
pubmed: 12557289
Brain. 2012 Jun;135(Pt 6):1819-33
pubmed: 22561643
Clin Immunol. 2010 Oct;137(1):51-9
pubmed: 20621566
Am J Pathol. 1993 Aug;143(2):555-64
pubmed: 7688186
Nat Med. 1999 Feb;5(2):170-5
pubmed: 9930864
Ann Neurol. 2018 Apr;83(4):739-755
pubmed: 29518260
J Neuroimmunol. 2015 Jun 15;283:64-9
pubmed: 26004159
Ann Neurol. 2018 May;83(5):1032-1036
pubmed: 29665046
J Neurol. 2018 Feb;265(2):424-430
pubmed: 29273846
Acta Neuropathol. 2015 Dec;130(6):765-81
pubmed: 26511623
J Neuroinflammation. 2012 May 16;9:93
pubmed: 22591862
Acta Neurol Scand. 1989 Sep;80(3):238-47
pubmed: 2801020
Clin Neurol Neurosurg. 2017 Sep;160:27-29
pubmed: 28622533
Autoimmun Rev. 2005 Sep;4(7):460-7
pubmed: 16137612
Cold Spring Harb Perspect Biol. 2015 Sep 09;8(1):a020560
pubmed: 26354893
Nat Immunol. 2018 Jul;19(7):696-707
pubmed: 29925992
J Clin Invest. 2005 Jan;115(1):187-94
pubmed: 15630459
Eur J Neurol. 2007 Aug;14(8):907-11
pubmed: 17662013
Brain. 2006 Jan;129(Pt 1):200-11
pubmed: 16280350
Nat Rev Neurosci. 2019 Dec;20(12):728-745
pubmed: 31712781
Brain. 2016 Mar;139(Pt 3):807-15
pubmed: 26912645
J Neuroimmunol. 2017 Aug 15;309:88-99
pubmed: 28601295