| 1. |
- Greco, Raffaella, et al.
(author)
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Innovative cellular therapies for autoimmune diseases : expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee
- 2024
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In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 69
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Journal article (peer-reviewed)abstract
- Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert -based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 2. |
- Katsarogiannis, Evangelos, et al.
(author)
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Evoked potentials after autologous hematopoietic stem cell transplantation for multiple sclerosis
- 2024
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In: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 83
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Journal article (peer-reviewed)abstract
- Objective: To investigate the effect of autologous hematopoietic stem cell transplantation (AHSCT) on functional aspects of the nervous system assessed by visual (VEP), somatosensory (SEP), and motor (MEP) evoked potentials in patients with relapsing -remitting multiple sclerosis. Background: Several studies have demonstrated the efficacy of AHSCT on inflammatory activity and disability progression in patients with multiple sclerosis. However, the impact of AHSCT on evoked potentials has not been evaluated before. Methods: Twelve AHSCT-treated patients from Uppsala University Hospital were consecutively recruited. Evoked potentials (EP) were collected at baseline and two follow-up visits, 3 and 12 months post-AHSCT. We calculated a composite EP score for each participant and compared it between different time points. Results: The median total EP score decreased from 5 at baseline, to 2.5 at 12 months post-ASHCT (p = 0.008). A significant improvement in tibial SEP (tSEP) latencies was observed (42.7 vs 41.5 ms, p < 0.001), with a similar trend for MEP latencies 12 months post-ASHCT. No significant changes in median SEP or VEP latencies were observed. Conclusions: Treatment with AHSCT was associated with improved transmission in some central nervous system pathways in multiple sclerosis patients.
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| 3. |
- Pavlovic, Ivan, et al.
(author)
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Cerebrospinal fluid mtDNA concentrations are increased in multiple sclerosis and were normalized after intervention with autologous hematopoietic stem cell transplantation
- 2024
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In: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 84
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Journal article (peer-reviewed)abstract
- BackgroundMitochondrial DNA (mtDNA) is a pro-inflammatory damage-associated molecular pattern molecule and could be an early indicator for inflammation and disease activity in MS. Autologous hematopoietic stem cell transplantation (aHSCT) is a potent treatment for MS, but its impact on mtDNA levels in cerebrospinal fluid (CSF) remains unexplored.ObjectivesTo verify elevated CSF mtDNA concentrations in MS patients and assess the impact of aHSCT on mtDNA concentrations.MethodsMultiplex droplet digital PCR (ddPCR) was used to quantify mtDNA and nuclear DNA in 182 CSF samples. These samples were collected from 48 MS patients, both pre- and post-aHSCT, over annual follow-ups, and from 32 healthy controls.ResultsCSF ccf-mtDNA levels were higher in patients with MS, correlated to multiple clinical and analytical factors and were normalized after intervention with aHSCT. Differences before aHSCT were observed with regard to MRI-lesions, prior treatment and number of relapses in the last year prior to aHSCT.ConclusionOur findings demonstrate elevated CSF mtDNA levels in MS patients, which correlate with disease activity and normalize following aHSCT. These results position mtDNA as a potential biomarker for monitoring inflammatory activity and response to treatment in MS.
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| 4. |
- Tigchelaar, Celien, et al.
(author)
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Cerebrospinal fluid and plasma concentrations of the inflammatory marker soluble CD27 in a large surgical population
- 2024
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In: iScience. - : Elsevier. - 2589-0042. ; 27:6
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Journal article (peer-reviewed)abstract
- Introduction: Soluble CD27 (sCD27) has the potential to serve as a biomarker for diseases involving immune system dysfunction. To inform interpretation of assay results, reference values are needed. So far, analysis of cerebrospinal fluid (CSF) sCD27 has mostly been performed in cohorts of patients with neuroinflammatory disorders, and general control data is missing. The aim of this study was therefore to determine reference ranges and to investigate the influence of factors such as age, comorbidity, blood-CSF-barrier (BCB) function (as assessed by the CSF/plasma albumin quotient (Qalb)) and inflammatory status markers, on CSF and plasma sCD27 concentrations in a relatively neurologically healthy surgical population. Methods: CSF and blood were collected from 486 patients undergoing spinal anaesthesia for elective surgery. Patient demographics, clinical data and the results of routine laboratory analyses were analysed for associations with sCD27 levels in CSF and plasma using a univariable and multivariable model. A healthy sub-cohort was selected based on an American Society of Anesthesiologists (ASA) physical status of I or II (healthy patient or with mild systemic disease), and inter alia, no history of cancer, immunological or neurological disorders, heavy tobacco use, or alcohol abuse. For the whole cohort, and the subpopulation of healthy patients we calculated reference intervals as the central 95% of the data.Results: In the total study group (age range 18 – 92 years, 57% male), median [range] CSF sCD27 concentration was 163 [<50 to 7474] pg/mL and median [range] plasma sCD27 concentration was 4624 [1830 to >400,000] pg/mL. In a multivariable model, plasma sCD27 concentration, age and Qalb were identified as most important for explaining the variability of CSF sCD27 levels. Reference sCD27 concentration intervals in the healthy sub-cohort were < 50 pg/mL – 419 pg/mL for CSF (n=125) and 2344 – 36422 pg/mL for plasma (n=158). Conclusions: Our data from a large group of patients reflecting a broad selection from the general population show that CSF sCD27 concentrations correlate with age and Qalb. These findings provide a solid foundation for interpreting sCD27 as clinical biomarker against a background of multiple socio-demographic and physiological aspects that may influence levels. Further studies to establish clinical CSF sCD27 cut-offs for central nervous system diseases should also account for the influence of age and blood-CSF-barrier function.
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| 5. |
- Tolf, Andreas, et al.
(author)
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Experiences of being treated with autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis : A qualitative interview study
- 2024
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 19:2
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Journal article (peer-reviewed)abstract
- BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) is increasingly used as a treatment for aggressive multiple sclerosis (MS) and has the potential to induce long-term remission and resolution of disease activity. Despite the extensive research on treatment outcome after AHSCT, the experience of living with MS after AHSCT has not been previously described in the scientific literature. The aim of this study was to explore long-term lived experience of people with MS treated with AHSCT.Methods and findingsTo exclude selection bias, all persons treated with AHSCT for MS at Uppsala University Hospital, Sweden, between 2004 and 2007 (n = 10), were asked to participate in the study, and all accepted. Open-ended interviews were conducted, digitally recorded, transcribed verbatim, and then subjected to qualitative content analysis with an inductive approach. Five main themes emerged from the interviews: (I) being diagnosed with MS–an unpredictable existence; (II) a new treatment–a possibility for a new life; (III) AHSCT–a transition; (IV) reclaiming life; and (V) a bright future accompanied by insecurity. AHSCT was described by the participants in terms of a second chance and an opportunity for a new life. The treatment became a transition from a state of illness to a state of health, enabling a previous profound uncertainty to wane and normality to be restored. Although participants of different age and sex were included, the main limitation of this study is the relatively small number of participants. Also, the inclusion of persons from one centre alone could restrict transferability of the results.ConclusionsThe results give a first insight into lived experience following a highly effective induction treatment for MS, and the experience of not having MS anymore. Underpinned by previously described outcome following AHSCT, the results of this study challenge the current view on MS as a chronic disease with no possible cure.
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