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Markers of immunosenescence in the peripheral blood of multiple sclerosis subjects compared to healthy controls

Jamann, Hélène; Clénet, Marie-Laure; Charabati, Marc; Mamane, Victoria; Ouédraogo, Oumarou; Carmina Moratalla, Ana; Muccilli, Alexandra; Daigneault, Audrey; Duguette, Pierre; Rousseau, Marie-Claude; Arbour, Nathalie; Larochelle, Catherine . Markers of immunosenescence in the peripheral blood of multiple sclerosis subjects compared to healthy controls In: 34e Congress of the European Comitee for Treatment and Research in Multiple Sclerosis, 10-12 October, 2018, Berlin, Germany.

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Résumé

Introduction: Alterations of the immune profile due to biological aging is called immunosenescence. Immunosenescence contributes to a state of low grade inflammation and decreased capacity for neuroglial repair observed upon aging. This process is influenced not only by genetic but also environmental factors such as repeated antigen encounter and chronic viral infections. Recent studies suggest that autoimmune and inflammatory diseases such as multiple sclerosis (MS) are associated with premature immunosenescence. Older age being the strongest predictive factor for onset of progression in MS, we hypothesize that age-sensitive immune markers could represent relevant biomarkers for progression in MS.

Objectives/aims: To characterize the expression of age-sensitive immune markers in the peripheral blood of untreated MS, treated MS and control subjects.

Methods: We measured by flow cytometry the proportion of T cells, B cells, NK cells and monocytes expressing CD27, CD28, CD57 and CD70 in the peripheral blood of MS patients and healthy controls between 20 and 75 y.o. We assessed levels of IL-4, IL-10, IL-18, TNF, leptin and BDNF in their sera. Relations between immune markers and age, disease duration, EDSS, relapses, treatment status and number of T2 lesions were estimated with correlations and linear regression. We will proceed to cross-sectional analysis of a total of 200 MS subjects and 150 healthy controls (HC).

Results: Preliminary results based on analysis of 80 MS patients and 50 healthy controls show that the CD4:CD8 ratio is higher in MS than in HC and that this difference is accentuated upon aging in untreated MS. TNF levels increase upon aging and show a stronger correlation with aging than with disease duration in MS subjects. IL-18 is correlated with age in all populations, and more strongly in untreated MS subjects. Women show higher leptin levels than men and MS subjects display higher levels than age/sex matched HC, at all ages. BDNF levels decrease upon aging in active/progressive MS subjects but are stable in benign MS. People with MS treated with first-line injectables tend to exhibit an immune profile closer to HC of the same age. Conclusions: Markers of immunosenescence are altered in MS compared to age/sex-matched HC. We will assess immunosenescence as a predictor of disease progression in MS. The future study will be funded by the Grant for Multiple Sclerosis Innovation from Merck/EMD-Serono.

Disclosure: The future study will be funded by the Grant for Multiple Sclerosis Innovation (GMSI) from Merck/EMD-Serono. H.J. receives a scholarship from the Department of Neurosciences from the University of Montreal. M-L.C. and M.C. receive a scholarship from the MS Society of Canada. A.C.M receives a scholarship from the MS Society of Canada and FRQS. O.O. receives a scholarship from the Programme Canadien des bourses de la Francophonie (PCBF). C.L. holds a FRQ-S junior 1 award. H.J. has no conflict of interest to declare in relation to this project. M-L. C. has no conflict of interest to declare in relation to this project.M.C. has no conflict of interest to declare in relation to this project. V.M. has no conflict of interest to declare in relation to this project. O.O. has no conflict of interest to declare in relation to this project. A.C.M. has no conflict of interest to declare in relation to this project. A.M. has no conflict of interest to declare in relation to this project. A.D. has no conflict of interest to declare in relation to this project. P.D. has served on scientific advisory boards and as speaker for EMD-Serono, Biogen, Roche, Novartis, Teva, Celgene, Actelion and Sanofi-Genzyme. M-C.R. has no conflict of interest to declare in relation to this project. N.A. has received honorarium as speaker from Novartis. C.L. has served on scientific advisory boards and as speaker for EMD-Serono, Biogen, Roche, Novartis, Teva, Celgene, Actelion and Sanofi-Genzyme and has received travel support from Sanofi-Genzyme.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Multiple Sclerosis Journal 24(suppl 2); 1-1066 affiche scientifique P1185
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 07 août 2019 16:20
Dernière modification: 07 août 2019 16:20
URI: http://espace.inrs.ca/id/eprint/8133

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