No Impact of Long-Term Fingolimod Treatment on Fecal Secretory Immunoglobulin A Levels in Patients With Multiple Sclerosis.
fingolimod
gut immune system
microbiome
multiple sclerosis
sIgA
secretory immunglobulin A
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2020
2020
Historique:
received:
30
05
2020
accepted:
07
09
2020
entrez:
26
10
2020
pubmed:
27
10
2020
medline:
27
10
2020
Statut:
epublish
Résumé
Fingolimod (FTY) is a sphingosine 1 phosphate (S1P) agonist with significant effects on immune cell distribution used as an effective disease modifying therapy in multiple sclerosis (MS) patients. Animal studies have demonstrated that a dysregulation of egress of murine secretory Immunglobulin A (sIgA)+ plasmablasts from Peyer's patches in FTY-treated mice reduced fecal sIgA levels. Alterations in intestinal levels of sIgA could modify the gut microbiome and homeostasis in humans. We analyzed the effect of FTY on the fecal and salivary sIgA levels as marker of the humoral immune system in the gut. Twenty five people with confirmed MS diagnosis according to 2010 revised McDonald's criteria and on long-term continuous treatment at the MS Center in Dresden, Germany were enrolled in this exploratory cross-sectional study. Fecal and salivary sIgA were analyzed after at least 12 months of treatment with FTY or Glatiramer acetate (GA). Fifteen MS patients on FTY and 10 on GA participated in this study. The mean fecal sIgA concentration of both groups was not decreased compared to reference values and did not demonstrate significant differences between them (FTY 3323.13 μg/g +/- 2094.72; GA 2040.65 μg/g +/- 1709.07). A similar pattern was seen in the salivary sIgA and serum immunoglobulins levels. In this pilot study, we could not confirm the decrease of fecal sIgA after a long-term treatment with FTY. Further longitudinal studies should evaluate the effects of MS treatments on the gut immune system in more detail.
Sections du résumé
BACKGROUND
BACKGROUND
Fingolimod (FTY) is a sphingosine 1 phosphate (S1P) agonist with significant effects on immune cell distribution used as an effective disease modifying therapy in multiple sclerosis (MS) patients. Animal studies have demonstrated that a dysregulation of egress of murine secretory Immunglobulin A (sIgA)+ plasmablasts from Peyer's patches in FTY-treated mice reduced fecal sIgA levels. Alterations in intestinal levels of sIgA could modify the gut microbiome and homeostasis in humans. We analyzed the effect of FTY on the fecal and salivary sIgA levels as marker of the humoral immune system in the gut.
METHODS
METHODS
Twenty five people with confirmed MS diagnosis according to 2010 revised McDonald's criteria and on long-term continuous treatment at the MS Center in Dresden, Germany were enrolled in this exploratory cross-sectional study. Fecal and salivary sIgA were analyzed after at least 12 months of treatment with FTY or Glatiramer acetate (GA).
RESULTS
RESULTS
Fifteen MS patients on FTY and 10 on GA participated in this study. The mean fecal sIgA concentration of both groups was not decreased compared to reference values and did not demonstrate significant differences between them (FTY 3323.13 μg/g +/- 2094.72; GA 2040.65 μg/g +/- 1709.07). A similar pattern was seen in the salivary sIgA and serum immunoglobulins levels.
CONCLUSION
CONCLUSIONS
In this pilot study, we could not confirm the decrease of fecal sIgA after a long-term treatment with FTY. Further longitudinal studies should evaluate the effects of MS treatments on the gut immune system in more detail.
Identifiants
pubmed: 33102475
doi: 10.3389/fcell.2020.567659
pmc: PMC7546410
doi:
Types de publication
Journal Article
Langues
eng
Pagination
567659Informations de copyright
Copyright © 2020 Inojosa, Eisele, Proschmann, Zeissig, Akgün and Ziemssen.
Références
Cell. 2019 Jan 24;176(3):610-624.e18
pubmed: 30612739
J Immunol. 2002 Aug 15;169(4):1844-51
pubmed: 12165508
Infect Immun. 2012 Aug;80(8):2712-23
pubmed: 22615252
Mult Scler Relat Disord. 2020 Jan;37:101427
pubmed: 32172998
Curr Biol. 2018 Sep 24;28(18):R1117-R1119
pubmed: 30253156
Front Neurol. 2020 May 12;11:391
pubmed: 32477253
Ann Clin Transl Neurol. 2020 Apr;7(4):406-419
pubmed: 32162850
Crit Rev Biochem Mol Biol. 2017 Feb;52(1):45-56
pubmed: 27841019
Front Immunol. 2018 Mar 06;9:439
pubmed: 29559977
Physiol Rev. 2010 Jul;90(3):859-904
pubmed: 20664075
Clin Transl Gastroenterol. 2020 Mar;11(3):e00146
pubmed: 32352710
Mucosal Immunol. 2011 Nov;4(6):603-11
pubmed: 21975936
Front Immunol. 2013 Aug 06;4:222
pubmed: 23964273
J Immunol. 2008 Apr 15;180(8):5335-43
pubmed: 18390715
Nat Microbiol. 2016 Jul 04;1(9):16103
pubmed: 27562257
Scand J Immunol. 2009 Dec;70(6):505-15
pubmed: 19906191
Front Immunol. 2018 Nov 20;9:2669
pubmed: 30524432
Expert Opin Pharmacother. 2017 Oct;18(15):1649-1660
pubmed: 28844164
Nat Rev Drug Discov. 2010 Nov;9(11):883-97
pubmed: 21031003
J Crohns Colitis. 2018 Aug 22;12(suppl_2):S678-S686
pubmed: 28961752
Int J Mol Sci. 2018 Jan 29;19(2):
pubmed: 29382132
Ann Neurol. 2011 Feb;69(2):292-302
pubmed: 21387374
Blood. 2007 May 1;109(9):3749-56
pubmed: 17234743
Gut. 1996 Mar;38(3):348-54
pubmed: 8675085
Front Immunol. 2017 Apr 27;8:476
pubmed: 28496443
J Lipid Res. 2014 Aug;55(8):1596-608
pubmed: 24459205
Beijing Da Xue Xue Bao Yi Xue Ban. 2016 Dec 18;48(6):987-993
pubmed: 27987502
Immunology. 2020 Jan;159(1):52-62
pubmed: 31777063
J Biomed Sci. 2019 Aug 21;26(1):59
pubmed: 31434568
JAMA Neurol. 2013 Oct;70(10):1315-24
pubmed: 23921521
J Neuroinflammation. 2017 Feb 23;14(1):41
pubmed: 28231856
Cell. 2014 Aug 28;158(5):1000-1010
pubmed: 25171403
J Immunol. 2009 Nov 1;183(9):5879-85
pubmed: 19828639
J Immunol. 2007 Jan 1;178(1):27-32
pubmed: 17182536
J Neuroinflammation. 2019 Nov 21;16(1):231
pubmed: 31752913
J Immunol. 2008 Feb 1;180(3):1921-8
pubmed: 18209090