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      Assessment of Functional Capacity of Immune System in Patients with Multiple Sclerosis using QuantiFERON Monitor

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          Abstract

          Background

          The QuantiFERON®-Monitor (QFM) is an assay that measures interferon- γ production and was developed to provide an objective marker of complex immune response. In this study, we evaluated the use of the QFM test in patients with two forms of multiple sclerosis (MS), relapsing–remitting form treated with fingolimod (fMS) and secondarily progressive form not treated pharmacologically (pMS), and in healthy controls (HC). We hypothesized that IFN- γ levels would be lower in those subjects who are relatively more immunosuppressed and higher in those with normal or activated immune function.

          Methods

          This single-center observational study was conducted from November 2020 to October 2021 and compared results in three groups of patients: 86 healthy controls, 96 patients with pMS, and 78 fMS. Combination of lyophilized stimulants was added to 1 ml heparinized whole blood within 8 hr of collection. Plasmatic IFN- γ was measured using the ELISA kit for the QFM and data were obtained in IU/ml.

          Results

          The results showed that controls had nearly 2-fold higher levels of IFN- γ (QFM score) in median (q25, q75) 228.00 (112.20, 358.67) than the MS patient groups: pMS 144.80 (31.23, 302.00); fMS 130.50 (39.95, 217.07) which is statistically significant difference P-value: HC vs. pMS = 0.0071; HC vs. fMS = 0.0468. This result was also confirmed by a validation analysis to exclude impact of variable factors, such as disease duration and Expanded Disability Status Scale scores.

          Conclusions

          Results showed that controls had higher levels of IFN- γ production than the MS patient groups and suggest that MS patients included in this study have a lower ability of immune system activation than HC. Results confirm that fingolimod is able to suppress production of IFN- γ. The fact that the QFM score of MS patients is significantly lower than that of HC may indicate a dysfunctional state of the immune system in baseline conditions.

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          Most cited references30

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          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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            Defining the clinical course of multiple sclerosis

            Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.
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              Role of the innate and adaptive immune responses in the course of multiple sclerosis.

              Multiple sclerosis is a chronic disease of the CNS that leads to substantial disability in most patients. The early phase is characterised by relapses and the later phase by progressive disability. Results from immunological, genetic, and histopathological studies and treatment trials have shown that the immune system plays a key part in the disease course. Findings from animal models and immunological studies of patients with multiple sclerosis suggest a change in the involvement of the immune system during disease initiation and progression. These findings suggest that a peripheral immune response targeting the CNS drives the disease process during the early phase, whereas immune reactions within the CNS dominate the progressive phase. These concepts for the differential involvement of immune responses in the early and progressive phase of this disease have important implications for future research in the pathogenesis and treatment of multiple sclerosis.
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                Author and article information

                Contributors
                Journal
                J Immunol Res
                J Immunol Res
                jir
                Journal of Immunology Research
                Hindawi
                2314-8861
                2314-7156
                2023
                7 April 2023
                : 2023
                : 4653627
                Affiliations
                1Department of Neurology, Faculty of Medicine and University Hospital Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic
                2Department of Clinical Immunology and Allergology, University Hospital Hradec Králové, Hradec Králové, Czech Republic
                3Department of Neurology, University Hospital and Masaryk University, Brno, Czech Republic
                4Department of Neurology, Faculty of Medicine and University Hospital Plzen, Charles University in Prague, Plzeň, Czech Republic
                Author notes

                Academic Editor: Lele Zhu

                Author information
                https://orcid.org/0000-0002-1772-8781
                https://orcid.org/0000-0003-2778-6800
                https://orcid.org/0000-0001-8000-9766
                https://orcid.org/0000-0001-8071-2005
                https://orcid.org/0000-0003-1565-4181
                Article
                10.1155/2023/4653627
                10104739
                084c7338-1933-437b-bb3a-6c70eff299bd
                Copyright © 2023 Zbysek Pavelek et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 November 2022
                : 19 February 2023
                : 28 February 2023
                Funding
                Funded by: MH CZ – DRO
                Award ID: UHHK, 00179906
                Funded by: Ministerstvo Zdravotnictví Ceské Republiky
                Award ID: FN HK 00179906
                Funded by: Univerzita Karlova v Praze
                Award ID: PROGRES Q40/15
                Funded by: Univerzita Karlova v Praze
                Award ID: COOPERATION, NEUR
                Categories
                Research Article

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