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

• Published in: Frontiers in immunology Vol. 12; p. 685139
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 12.07.2021
• Subjects: adaptive immunity; aging; Immunology; inflammation; innate immunity; multiple sclerosis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.685139

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.