No Impact of Long-Term Fingolimod Treatment on Fecal Secretory Immunoglobulin A Levels in Patients With Multiple Sclerosis.

Hernan Inojosa,Tjalf Ziemssen,Katja Akgün,Judith Eisele,Undine Proschmann,Sebastian Zeissig

doi:10.3389/fcell.2020.567659

Hernan Inojosa, Tjalf Ziemssen + Show 4 more

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https://doi.org/10.3389/fcell.2020.567659

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Abstract

BackgroundFingolimod (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.MethodsTwenty 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).ResultsFifteen 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.ConclusionIn 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.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) induced by an imbalance of the immune-regulatory network
Functional antagonism of S1P-mediated signaling by FTY treatment selectively accumulated immunoglobulin A (IgA)+ plasmablasts in lymphatic regions of Peyer’s patches (PPs) and impaired the production of specific fecal IgA responses (Gohda et al, 2008). These findings suggest a relevant S1P signaling modulation of B cell function by FTY, reflected by a reduction of the plasmablast population in the intestinal lamina propria and resulting in an impairment of antigen-specific secretory Immunglobulin A (sIgA) production against orally administered antigens (Kunisawa et al, 2007; Kleinwort et al, 2018)
After 20.87 months (SD = 7.59) of treatment, fecal sIgA was not decreased in the FTY-treated patients in relationship to reference values

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) induced by an imbalance of the immune-regulatory network. Long-Term Fingolimod in Fecal sIgA first oral approved DMT for treatment of highly active forms of relapsing-remitting MS, is a sphingosine-1-phosphate (S1P) receptor modulator that regulates S1P-mediated lymphocyte trafficking from lymphoid tissues, impairing peripheral lymphocyte recirculation (Brinkmann et al, 2010; Thomas et al, 2017a). Fingolimod leads to a rapid reduction of absolute lymphocyte count in peripheral blood in addition to modulatory effects on antigen-presenting cells that mediate a rebalancing of auto-reactive immune responses in MS patients (Thomas et al, 2017b; Kaufmann et al, 2018; Sehr et al, 2020). 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. We analyzed the effect of FTY on the fecal and salivary sIgA levels as marker of the humoral immune system in the gut

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