Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis.
Adolescent
Adult
Female
Gastrointestinal Microbiome
/ immunology
Homeostasis
/ immunology
Humans
Immunoglobulin A
/ immunology
Immunoglobulin G
/ immunology
Male
Microbiota
/ immunology
Middle Aged
Multiple Sclerosis
/ immunology
Multiple Sclerosis, Relapsing-Remitting
/ immunology
Patient Acuity
RNA, Ribosomal, 16S
Young Adult
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
07
07
2020
accepted:
09
03
2021
entrez:
12
5
2021
pubmed:
13
5
2021
medline:
22
1
2022
Statut:
epublish
Résumé
Based on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS. We investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing. We show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction ( Gut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS.
Identifiants
pubmed: 33975914
pii: 8/4/e997
doi: 10.1212/NXI.0000000000000997
pmc: PMC8114833
pii:
doi:
Substances chimiques
Immunoglobulin A
0
Immunoglobulin G
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Mucosal Immunol. 2020 Jan;13(1):3-11
pubmed: 31413347
Gut. 2014 Oct;63(10):1566-77
pubmed: 24436141
Sci Rep. 2013 Dec 17;3:3515
pubmed: 24343271
Mult Scler. 2020 Nov;26(13):1658-1669
pubmed: 31610739
Eur J Neurol. 2016 Aug;23(8):1308-1321
pubmed: 27176462
Nat Immunol. 2018 Jun;19(6):617-624
pubmed: 29760533
J Clin Invest. 2011 May;121(5):1946-55
pubmed: 21490392
Sci Immunol. 2020 Nov 20;5(53):
pubmed: 33219152
Clin Immunol. 2013 Aug;148(2):209-18
pubmed: 23778260
Cell. 2019 Jan 24;176(3):610-624.e18
pubmed: 30612739
Front Microbiol. 2011 Aug 01;2:166
pubmed: 21904534
J Exp Med. 2020 Mar 2;217(3):
pubmed: 31891367
Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10719-10724
pubmed: 28893994
Gut. 2011 Nov;60(11):1506-19
pubmed: 21515549
J Allergy Clin Immunol. 2019 Apr;143(4):1575-1585.e4
pubmed: 30554723
Mult Scler. 2017 Mar;23(3):442-446
pubmed: 27270497
Nat Commun. 2016 Jun 28;7:12015
pubmed: 27352007
Neurol Neuroimmunol Neuroinflamm. 2020 Mar 2;7(3):
pubmed: 32123045
Lancet Neurol. 2012 Feb;11(2):157-69
pubmed: 22265211
Ann Neurol. 1996 Aug;40(2):181-7
pubmed: 8773599
Clin Vaccine Immunol. 2012 Apr;19(4):515-21
pubmed: 22336288
Lancet Neurol. 2018 Feb;17(2):162-173
pubmed: 29275977
PLoS One. 2020 Feb 21;15(2):e0228883
pubmed: 32084151
Mult Scler. 2015 Jul;21(8):1013-24
pubmed: 25680984
Neurol Neuroimmunol Neuroinflamm. 2018 Oct 26;6(1):e517
pubmed: 30568995
PLoS One. 2015 Sep 14;10(9):e0137429
pubmed: 26367776
Ann Neurol. 2016 Sep;80(3):443-7
pubmed: 27398819
Ann Neurol. 2011 Feb;69(2):292-302
pubmed: 21387374
Cell Host Microbe. 2018 Mar 14;23(3):302-311.e3
pubmed: 29478774
J Clin Microbiol. 2006 Jun;44(6):2099-104
pubmed: 16757604
Nat Commun. 2016 May 20;7:11639
pubmed: 27198196
Neurology. 1983 Nov;33(11):1444-52
pubmed: 6685237
Science. 2018 Mar 9;359(6380):1156-1161
pubmed: 29590047
Sci Rep. 2016 Jun 27;6:28484
pubmed: 27346372
J Allergy Clin Immunol. 2019 Apr;143(4):1353-1354
pubmed: 30664890
Sci Transl Med. 2018 Mar 28;10(434):
pubmed: 29593104
J Allergy Clin Immunol. 2015 Nov;136(5):1378-86.e1-5
pubmed: 26014812
Immunity. 2017 Jul 18;47(1):118-134.e8
pubmed: 28709802
Sci Transl Med. 2018 May 2;10(439):
pubmed: 29720448
PLoS One. 2014 Sep 03;9(9):e106335
pubmed: 25184418
Science. 2019 Nov 15;366(6467):881-886
pubmed: 31727837
J Neuroimmunol. 2019 Aug 15;333:576966
pubmed: 31153015
Appl Environ Microbiol. 1997 Jul;63(7):2802-13
pubmed: 9212428
J Neuroimmunol. 2013 Sep 15;262(1-2):19-26
pubmed: 23768729
Ann Neurol. 2002 Jul;52(1):47-53
pubmed: 12112046
Nature. 2011 Oct 26;479(7374):538-41
pubmed: 22031325
Physiol Rev. 2011 Jan;91(1):151-75
pubmed: 21248165
Sci Transl Med. 2015 Feb 25;7(276):276ra24
pubmed: 25717097
N Engl J Med. 2013 Jan 31;368(5):407-15
pubmed: 23323867
Nat Protoc. 2016 Aug;11(8):1531-53
pubmed: 27466712
Ann Clin Transl Neurol. 2020 Apr;7(4):406-419
pubmed: 32162850
Lancet. 2005 Aug 13-19;366(9485):579-82
pubmed: 16099294
Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10713-10718
pubmed: 28893978
Cell. 2014 Aug 28;158(5):1000-1010
pubmed: 25171403
Arch Neurol. 2011 Jul;68(7):870-8
pubmed: 21403003
Mucosal Immunol. 2020 Jan;13(1):12-21
pubmed: 31740744
Ann Neurol. 2012 Jul;72(1):53-64
pubmed: 22807325
Cell. 2016 May 5;165(4):827-41
pubmed: 27153495
Nat Methods. 2010 May;7(5):335-6
pubmed: 20383131
Muscle Nerve. 2006 Feb;33(2):225-31
pubmed: 16270308