RT Journal Article
SR Electronic
T1 Evaluation of Age-Dependent Immune Signatures in Patients With Multiple Sclerosis
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1094
DO 10.1212/NXI.0000000000001094
VO 8
IS 6
A1 Melanie Eschborn
A1 Marc Pawlitzki
A1 Timo Wirth
A1 Christopher Nelke
A1 Steffen Pfeuffer
A1 Andreas Schulte-Mecklenbeck
A1 Lisa Lohmann
A1 Leoni Rolfes
A1 Katrin Pape
A1 Maria Eveslage
A1 Stefan Bittner
A1 Catharina C. Gross
A1 Tobias Ruck
A1 Heinz Wiendl
A1 Sven G. Meuth
A1 Luisa Klotz
YR 2021
UL http://nn.neurology.org/content/8/6/e1094.abstract
AB 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.CM=central memory; CTLA-4=cytotoxic T lymphocyte–associated protein 4; DMT=disease-modifying therapy; DNAM-1=DNAX accessory molecule-1; EAE=experimental autoimmune encephalomyelitis; EDSS=Expanded Disability Status Scale; EM=effector memory; HD=healthy donor; IFN-γ=interferon-gamma; KLRG1=killer cell lectin-like receptor subfamily G member 1; LAG3=lymphocyte-activation gene 3; MFI=mean fluorescence intensity; MS=multiple sclerosis; NIC=noninflammatory control; NK=natural killer; PB=peripheral blood; PBMC=peripheral blood mononuclear cell; PPMS=primary progressive multiple sclerosis; RA=rheumatoid arthritis; RRMS=relapsing-remitting multiple sclerosis; sNfL=serum neurofilament light chain; SLE=systemic lupus erythematosus; TNF-α=tumor necrosis factor alpha