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

Abstract

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: 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: 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: 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.

Impact of Disease-Modifying Therapies on Gut–Brain Axis in Multiple Sclerosis

“…Intestinal IgAs play a critical role in the defense against external pathogens and in maintaining intestinal homeostasis, as they are part of the complex system necessary to maintain the correct gut permeability [70]. However, an exploratory study showed no reduction in secretory IgA in fecal samples of people with MS after long-term treatment with FTY [71].…”

“…Sphingosine-1-phosphate receptor modulators [52,[66][67][68][69][70][71][72] Induction of Treg activity in the gut mucosa Inhibition of epsilon toxin-secreting Clostridium perfringens Natalizumab [75][76][77] Reduction in T-cell trafficking in the gut mucosa Anti-CD20 monoclonal antibodies [82][83][84][85] Maintenance of intestinal barrier homeostasis Increase in anti-inflammatory species and decrease in inflammatory species…”

Microbiota, IgA and Multiple Sclerosis

“…Fingolimod treatment, which targets this receptor, resulted in the reduction in B cells and IgA production in mice. Secretory IgA concentrations in stools and saliva were equivalent in MS patients treated with fingolimod compared to GA-treated MS patients [ 162 ]. A comparison with untreated patients would be very informative.…”