Identification of the Immunological Changes Appearing in the CSF During the Early Immunosenescence Process Occurring in Multiple Sclerosis

Front Immunol. 2021 Jul 12:12:685139. doi: 10.3389/fimmu.2021.685139. eCollection 2021.

Abstract

Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.

Keywords: adaptive immunity; aging; inflammation; innate immunity; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / cerebrospinal fluid
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / blood
  • B-Lymphocytes / immunology
  • B7-H1 Antigen / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid
  • Female
  • Humans
  • Immunosenescence / immunology*
  • Linear Models
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology*
  • Multivariate Analysis
  • Oligoclonal Bands / immunology*
  • T-Lymphocytes / immunology
  • Young Adult

Substances

  • Antibodies, Viral
  • B7-H1 Antigen
  • Biomarkers
  • Chitinase-3-Like Protein 1
  • Oligoclonal Bands
  • activin A
  • Activins