Aging-dependent Change in Th17 and Cytokine Response in Multiple Sclerosis

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 18, 2024

Abstract Background Multiple sclerosis (MS) is a chronic autoimmune disease damaging the central nervous system. Diminished inflammatory activity (DA) as people with MS (pwMS) age motivated randomized clinical trials assessing disease-modifying therapy (DMT) discontinuation in older pwMS given concern for risks outweighing benefits. This study aims to examine whether peripheral production of Myelin Basic Protein (MBP)-driven cytokine responses mediate aging-associated decline DA. Methods We included data 669 adult between 2017 and 2022 who enrolled clinic-based prospective cohort. From subset 80 participants, we isolated fresh blood mononuclear cells (PBMCs) cultured 50μg/ml MBP (or heat-killed Candida) 24 hours. assayed cell culture supernatants interleukin 17 (IL-17) interferon gamma (IFN-γ) using Enzyme-Linked Immunosorbent Assay supernatant samples commercial human cytokine/chemokine array. examined associations annualized relapse rate (ARR) well MBP-stimulated (by PBMC) covariate-adjusted linear regressions. performed mediation analyses determine extent which MBP-driven response drives association ARR. Results Among (mean 51.7±12.7 years, 80.7% women, 89.4% non-Hispanic White), ARR declined (β=-0.003, p<0.001). subgroup whose PBMCs underwent ex vivo stimulation, IL-17 women (β=-0.27, p=0.04) but not men (β=-0.1, p=0.73). partially mediated lower (24.7% 15.3% men). In exploratory analyses, (≥50 years) had marginally (IL-4, MCP-2, MCP-3, PDGF-AA, PDGF-AB/BB) higher (Fractalkine, MDC) concentrations several cytokines than younger (<50 years), while certain (MCP-2, whereas others negated effect on Conclusion potential biological mechanism underlying aging-dependent DA warrants further investigation.

Язык: Английский

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Long-Term Disability Outcomes in Relapsing–Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(6), С. 1813 - 1813

Опубликована: Март 21, 2024

Background: Multiple sclerosis (MS) is a prevalent chronic inflammatory and neurodegenerative disease of the central nervous system. The main evolving forms, relapsing-remitting MS (RRMS) secondary progressive (SPMS), lack clear delineation. Methods: We conducted an observational study on 523 Caucasian RRMS patients receiving first-line disease-modifying therapies (DMTs), analyzing demographic, clinical, geographical data. Results: experienced statistically significant reduction in relapse rates post-DMT initiation. Significant differences time to reach Expanded Disability Status Score (EDSS) 3.0 6.0 were observed based demographics onset topography. Kaplan-Meier analysis revealed that with optic or supratentorial symptoms linked longer until EDSS = reached. Urban origin correlated prolonged 3.0. Gender environment showed no associations hazard reaching 6.0. Cox regression impact relapses scores our cohort. Conclusions: Multivariate identified several predictive factors for disability progression, including environment, age at onset, level DMT

Язык: Английский

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Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 15, 2024

Disease-modifying therapies (DMTs) have been shown to improve disease outcomes in multiple sclerosis (MS) patients. They may also impair the immune response vaccines, including SARS-CoV-2 vaccine. However, available data on both intrinsic effects of DMTs and their influence cellular vaccine are still incomplete.

Язык: Английский

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Roles of Hypoxia-Inducible Factor-Prolyl Hydroxylases in Aging and Disease

Ageing Research Reviews, Год журнала: 2024, Номер 102, С. 102551 - 102551

Опубликована: Окт. 22, 2024

Язык: Английский

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Exploring the role of sex hormones and gender diversity in multiple sclerosis

Nature Reviews Neurology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 11, 2024

Язык: Английский

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From Genesis to Old Age: Exploring the Immune System One Cell at a Time with Flow Cytometry

Biomedicines, Год журнала: 2024, Номер 12(7), С. 1469 - 1469

Опубликована: Июль 3, 2024

The immune system is a highly complex and tightly regulated that plays crucial role in protecting the body against external threats, such as pathogens, internal abnormalities, like cancer cells. It undergoes development during fetal stages continuously learns from each encounter with allowing it to develop immunological memory provide wide range of protection. Over time, after numerous encounters years functioning, can begin show signs erosion, which commonly named immunosenescence. In this review, we aim explore how responds initial antigens handles persistent stimulations throughout person's lifetime. Our understanding has greatly benefited advanced technologies flow cytometry. context, will discuss valuable contribution cytometry enhancing our knowledge behavior aging, specific focus on T-cells. Moreover, expand discussion cytometry-based assessment extracellular vesicles, recently discovered communication channel biology, their implications for functioning.

Язык: Английский

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SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells

Vaccines, Год журнала: 2024, Номер 12(8), С. 924 - 924

Опубликована: Авг. 17, 2024

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early progresses with age. B cells play a central role this process, contributing to cytokine production, defective regulatory functions, abnormal immunoglobulin even the nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ cells, are largely used treatment of both relapsing remitting (RR) progressive (PR) forms MS. Although effective against MS symptoms lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce immune response COVID-19 vaccination. By using high-parameter flow cytometry, we examined antigen-specific (Ag+) six months post-third mRNA vaccination patients RR PR on therapy. Despite lower Ag+ cell responses levels anti-SARS-CoV2, total neutralizing antibodies, developed strong T responses. We observed similar percentages numbers CD4+ high proportion CD8+ slight differences phenotype functionality; this, however, suggested presence driven age disease severity.

Язык: Английский

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Understanding the Complex Dynamics of Immunosenescence in Multiple Sclerosis: From Pathogenesis to Treatment

Biomedicines, Год журнала: 2024, Номер 12(8), С. 1890 - 1890

Опубликована: Авг. 19, 2024

Immunosenescence, the gradual deterioration of immune function with age, holds profound implications for our understanding and management multiple sclerosis (MS), a chronic autoimmune disease affecting central nervous system. Traditionally diagnosed in young adults, advancements disease-modifying therapies increased life expectancy have led to growing number older individuals MS. This demographic shift underscores need deeper investigation into how age-related alterations shape course MS, influencing progression, treatment effectiveness, overall patient outcomes. Age-related immunosenescence involves changes such as shifts cytokine profiles, accumulation senescent cells, compromised surveillance, collectively contributing state known "inflammaging". In context these immunological disturb intricate balance between inflammatory regulatory responses, thereby impacting mechanisms tolerance peripheral regulation. paper stands out by combining most recent both pathophysiological perspectives on sclerosis, offering cohesive accessible discussion that bridges theory practice, while also introducing novel insights underexplored concepts therapy discontinuation latest senolytic, neuroprotective, remyelination therapies. Enhancing complexities will guide tailored approaches MS management, ultimately improving clinical outcomes affected individuals.

Язык: Английский

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Review of evidence linking exposure to environmental stressors and associated alterations in the dynamics of immunosenescence (ISC) with the global increase in multiple sclerosis (MS)

Immunity & Ageing, Год журнала: 2024, Номер 21(1)

Опубликована: Окт. 22, 2024

Historical survey confirms that, over the latter part of 20th century, autoimmune-based diseases, including multiple sclerosis (MS), have shown a worldwide increase in incidence and prevalence. Analytical population studies established that exponential rise MS is not solely due to improvements diagnosis healthcare but relates an autoimmune risk factors. Harmful environmental exposures, non-communicable social determinants health, anthropogens indigenous or transmissible microbes, constitute group causal been closely linked with global cases. Exposure stressors has profound effects on adaptive arm immune system and, particular, associated intrinsic process ageing immunosenescence (ISC). Stressor-related disturbances dynamics ISC include cell-linked untimely premature (p) alterations accelerated replicative (ar) change. A recognised immune-associated feature pISC current evidence supports presence arISC during disease. Moreover, collated data illustrates characterise are inducible by strongly implicated causing duplicate changes cells MS. The close relationship between exposure factors induction offers valid mechanism through which pro-immunosenescent may act contribute recorded rate number new cases Confirmation provides rational valuable therapeutic target for use senolytic drugs either prevent accumulation enhance ablation less efficient senescent decelerate dysregulated proliferation. range senotherapeutics available kinase transcriptase inhibitors, rapalogs, flavanols genetically-engineered T selective treatments control emerging unspecified aspects discussed.

Язык: Английский

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Strategic De-escalation of Disease-Modifying Therapies in Elderly Patients: Approaches and Considerations

Current Treatment Options in Neurology, Год журнала: 2024, Номер 27(1)

Опубликована: Окт. 31, 2024

Язык: Английский

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