Allizond, Valeria

Banche, Giuliana

Cavalla, Paola

Cuffini, Annamaria

Musso, Tiziana

Scutera, Sara

Sparti, Rosaria

English

Scutera, Sara Agata Caterina

Institutional Research Information System University of Turin

P0606 The increased risk of microbial infections in multiple sclerosis patients:interplay between disease-modifying therapies and human phagocytesValeria Allizond1, Sara Scutera2, Rosaria Sparti*2, Paola Cavalla3, Tiziana Musso2, Anna Maria Cuffini1, GiulianaBanche31 Bacteriology Laboratory, Department of Public Health and Pediatrics, University of Torino, Turin, Italy., 2Immunology Laboratory, Department of Public Health and Pediatrics, University of Torino, Turin, Italy., 3Department of Neuroscience, University of Torino, Turin, Italy.Background: The risk infection in multiple sclerosis (MS) associated with MS treatments has become one of themost important factors in the therapy choice. The hospitalization high rates and infection-related mortality couldbe mainly attributed to disease-modifying therapy (DMT). DMT alters, at various extend, the innate immunityagainst pathogens. In this project, granted by an ESCMID research grant, the straightforward effect of the mostcommon MS DMTs on healthy subject (HS) neutrophil functions was examined in vitro.Materials/methods: To achieve this purpose HS polymorphonuclear cells (PMNs) were pre-treated with eitherimmunosuppressive ( i.e. natalizumab - NAT, fingolimod - FTY) or immunomodulatory ( i.e. interferonβ 1b – INFβ-b, glatiramer acetate - GA) drugs, and then their functional activity was investigated. In detail, PMN intracellularkilling activity towards Klebsiella pneumoniae, the cytokine release profile, the apoptosis, the ROS production andsurface molecule expression were evaluated.Results: In vitro assays with drug pre-treated HS PMNs showed a reduction in bacterial killing with statisticallysignificantly lower values (p<0.001) than those registered for the un-pre-treated controls for all the DMTs assayed(Figure 1). In the same experimental conditions variable results, depending on the DMT used, for the otherexamined neutrophil functions were achieved. The reduction in the intracellular killing activity of NAT pre-treatedPMNs was not accompanied by changes in the other functional parameters. On the contrary, this defectiveneutrophil killing was also associated with a significantly lower ROS production, a slight increase of survival andcytokine production with FTY pre-treatment, and with a lower cytokine release pattern in case of both INFβ-b andGA pre-treatment.Conclusions: As microbial killing is a PMN critical physiological function, involving various mechanisms andalthough apoptosis, ROS, and cytokine do not seem to have an impact on the differences observed in the defectivekilling capacity of PMNs from treated-MS patients, other mechanisms, due to PMN plasticity, might be involved.However, our promising results regarding pre-treatment assays, confirmed that the PMN impairment is stronglylinked to the treatment itself and may contribute to increase exacerbations and microbial infection onset. Thebalance of the overall risk versus benefit should be continuously re-evaluated during treatment.29TH ECCMID13-16 APRIL 2019 AMSTERDAM, NETHERLANDS POWERED BY M-ANAGE.COM 

The increased risk of microbial infections in multiple sclerosis patients: interplay between disease-modifying therapies and human phagocytes

https://iris.unito.it/bitstream/2318/1702526/1/P0606_Sparti.pdf

The increased risk of microbial infections in multiple sclerosis patients: interplay between disease-modifying therapies and human phagocytes

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