The TCR Repertoire Reconstitution in Multiple Sclerosis: Comparing One-Shot and Continuous Immunosuppressive Therapies

Natalizumab (NTZ) and autologous hematopoietic stem cell transplantation (AHSCT) are two successful treatments for relapsing-remitting multiple sclerosis (RRMS), an autoimmune T-cell-driven disorder affecting the central nervous system that is characterized by relapses interspersed with periods of complete or partial recovery. Both RRMS treatments have been documented to impact T-cell subpopulations and the T-cell receptor (TCR) repertoire in terms of clone frequency, but, so far, the link between T-cell naive and memory populations, autoimmunity, and treatment outcome has not yet been established hindering insight into the post-treatment TCR landscape of MS patients. To address this important knowledge gap, we tracked peripheral T-cell subpopulations (naïve and memory CD4+ and CD8+) across 15 RRMS patients before and after two years of continuous treatment (NTZ) and a single treatment course (AHSCT) by high-throughput TCRß sequencing. We found that the two MS treatments left treatment-specific multidimensional traces in patient TCRß repertoire dynamics with respect to clonal expansion, clonal diversity and repertoire architecture. Comparing MS TCR sequences with published datasets suggested that the majority of public TCRs belonged to virus-associated sequences. In summary, applying multi-dimensional computational immunology to a TCRß dataset of treated MS patients, we show that qualitative changes of TCRß repertoires encode treatment-specific in...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Abstract Mesenchymal stem cells (MSCs) have provided a promising tool for cell therapy. Umbilical cord (UC) is one of the best sources of MSCs since its collection is noninvasive, and effortless, and the cells from this source are more capable and prolific. It has been proven that the differentiation, migration and protective properties of UC-MSCs are superior compared with other kinds of stem cells. Moreover, incurable neurodegenerative diseases, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease and Huntington, encourage scientists to apply UC-MSCs transplantation in order to find a definite tr...
Source: Regenerative Medicine - Category: Genetics & Stem Cells Authors: Tags: Regen Med Source Type: research
CONCLUSIONS: Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available. PMID: 32436209 [PubMed - in process]
Source: Revista de Neurologia - Category: Neurology Authors: Tags: Rev Neurol Source Type: research
Abstract Multiple disease-modifying medications with regulatory approval to treat multiple sclerosis (MS) are unable to prevent inflammatory tissue damage in the central nervous system (CNS), and none directly promote repair. Thus, there is an unmet clinical need for therapies that can arrest and reverse the persistent accumulation of disabilities associated with progressive forms of MS (P-MS). Preclinical research has revealed an unexpected ability of neural stem cell (NSC) therapies to provide neurotrophic support and inhibit detrimental host immune responses in vivo following transplantation into the chronicall...
Source: Trends in Molecular Medicine - Category: Molecular Biology Authors: Tags: Trends Mol Med Source Type: research
Conclusion: ASCT can be done safely for patients with relatively high EDSS scores with additional precautions for screening for infections. RRMS patients with the active disease show most improvement. SPMS patients may not show significant improvement in the short term.
Source: Neurology India - Category: Neurology Authors: Source Type: research
Complications involving the central nervous system (CNS) occur in 9–14% of patients following allogeneic hematopoietic stem cell transplantation (HSCT), including stroke-like episodes, demyelination, encephalitis, and nonspecific neurological symptoms. Here we report a case of multiple sclerosis (MS) like relapsing remitting encephalomyelitis following allogeneic HSCT, which did not respond to disease modifying therapies (DMTs) and “domino” autologous HSCT. A 53-year-old male was treated with allogeneic HSCT for lymphoid blast transformation of chronic myeloid leukemia. Ten months later he presented with ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Publication date: Available online 29 April 2020Source: Multiple Sclerosis and Related DisordersAuthor(s): Lídia Hau, Krisztián Kállay, Gabriella Kertész, Vera Goda, Csaba Kassa, Orsolya Horváth, Zoltán Liptai, Tamás Constantin, Gergely Kriván
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
AbstractThe majority of disease-modifying drugs (DMDs) available for the management of active relapsing –remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimeth yl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treat...
Source: Neurology and Therapy - Category: Neurology Source Type: research
Abstract Multiple sclerosis (MS) is a chronic, inflammatory autoimmune disease that affects the central nervous system (CNS) for which there is no cure. In MS, encephalitogenic T cells infiltrate the CNS causing demyelination and neuroinflammation; however, little is known about the role of regulatory T cells (Tregs) in CNS tissue repair. Transplantation of neural stem and progenitor cells (NSCs and NPCs) is a promising therapeutic strategy to promote repair through cell replacement, although recent findings suggest transplanted NSCs also instruct endogenous repair mechanisms. We have recently described that dampe...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Abstract Stem cell therapy is applicable for repair and replacement of damaged cells and tissues. Apart from transplanting cells to the body, the stem cell therapy directs them to grow new and healthy tissues. Stem cells in the area of regenerative medicines hold tremendous promise that may help to regenerate the damaged tissues and heal various diseases like multiple sclerosis, heart diseases, and Parkinson's diseases, and so on. To prove the safety, efficacy, and for the requirement of a licence for manufacture and sale, all the stem cell therapies should pass the required criteria and undergo certain examinatio...
Source: Current Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Curr Stem Cell Res Ther Source Type: research
In this study, EAE mouse model was established by MOG35-55 immunization method. Outcomes of the EAE mice in terms of body weight and clinical symptoms were analyzed. Electromyography (EMG) was performed to evaluate nerve conduction. ELISA was applied to quantify inflammatory cytokine levels in serum. Our results showed that IFN-γ could up-regulate protein expression of indoleamine 2, 3-dioxygenease 1 (IDO1), an important molecule released by MSCs to exert their immune suppressive activity (p 
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
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