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

• Main Authors: Carmen Picón, Amalia Tejeda-Velarde, José Ignacio Fernández-Velasco, Manuel Comabella, Roberto Álvarez-Lafuente, Ester Quintana, Susana Sainz de la Maza, Enric Monreal, Noelia Villarrubia, José Carlos Álvarez-Cermeño, María Inmaculada Domínguez-Mozo, Lluís Ramió-Torrentà, Eulalia Rodríguez-Martín, Ernesto Roldán, Yolanda Aladro, Silvia Medina, Mercedes Espiño, Jaime Masjuan, Clara Matute-Blanch, Marta Muñoz-San Martín, Carmen Espejo, Carmen Guaza, Alfonso Muriel, Lucienne Costa-Frossard, Luisa María Villar
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-07-01
• Series: Frontiers in Immunology
• Subjects: multiple sclerosis; aging; innate immunity; adaptive immunity; inflammation
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2021.685139/full

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.