Evaluation of Age-Dependent Immune Signatures in Patients With Multiple Sclerosis
Melanie Eschborn1, Marc Pawlitzki1, Timo Wirth1
1From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.
Background And Objectives:
In MS, an age-related decline in disease activity and a decreased efficacy of disease-modifying treatment have been linked to immunosenescence, a state of cellular dysfunction associated with chronic inflammation.
Methods:
To evaluate age-related immunologic alterations in MS, we compared immune signatures in peripheral blood (PB) and CSF by flow cytometry in patients with relapsing-remitting (RR) (PB n = 38; CSF n = 51) and primary progressive (PP) MS (PB n = 40; CSF n = 36) and respective controls (PB n = 40; CSF n = 85).
Results:
Analysis revealed significant age-related changes in blood immune cell composition, especially in the CD8 T-cell compartment of healthy donors (HDs) and patients with MS. However, HDs displayed a strong age-dependent decline in the expression of the immunoregulatory molecules KLRG1, LAG3, and CTLA-4 on memory CD8 T cells, whereas this age-dependent reduction was completely abrogated in patients with MS. An age-dependent increase in the expression of the costimulatory molecule CD226 on memory CD8 T cells was absent in patients with MS. CD226 expression correlated with disability in younger (≤50 years) patients with MS. CSF analysis revealed a significant age-dependent decline in various immune cell populations in PPMS but not RRMS, suggesting a differential effect of aging on the intrathecal compartment in PPMS.
Discussion:
Our data illustrate that aging in MS is associated with a dysbalance between costimulatory and immunoregulatory signals provided by CD8 T cells favoring a proinflammatory phenotype and, more importantly, a pattern of premature immune aging in the CD8 T-cell compartment of young patients with MS with potential implications for disease severity.
