AUTHOR=Picón Carmen , Tejeda-Velarde Amalia , Fernández-Velasco José Ignacio , Comabella Manuel , Álvarez-Lafuente Roberto , Quintana Ester , Sainz de la Maza Susana , Monreal Enric , Villarrubia Noelia , Álvarez-Cermeño José Carlos , Domínguez-Mozo María Inmaculada , Ramió-Torrentà Lluís , Rodríguez-Martín Eulalia , Roldán Ernesto , Aladro Yolanda , Medina Silvia , Espiño Mercedes , Masjuan Jaime , Matute-Blanch Clara , Muñoz-San Martín Marta , Espejo Carmen , Guaza Carmen , Muriel Alfonso , Costa-Frossard Lucienne , Villar Luisa María TITLE=Identification of the Immunological Changes Appearing in the CSF During the Early Immunosenescence Process Occurring in Multiple Sclerosis JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.685139 DOI=10.3389/fimmu.2021.685139 ISSN=1664-3224 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.