Quantiferon Monitor Testing Sheds Light on Immune System Disparities between Multiple Sclerosis Patients and Healthy Individuals
Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články
Grantová podpora
00179906
MH CZ - DRO (UHHK)
00179906
Ministry of Health of the Czech Republic
NEURO
Cooperation Program
PubMed
38396856
PubMed Central
PMC10889671
DOI
10.3390/ijms25042179
PII: ijms25042179
Knihovny.cz E-zdroje
- Klíčová slova
- fingolimod, immunity, multiple sclerosis,
- MeSH
- antagonista receptoru pro interleukin 1 MeSH
- cytokiny MeSH
- imunitní systém MeSH
- interferon gama MeSH
- lidé MeSH
- roztroušená skleróza * diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antagonista receptoru pro interleukin 1 MeSH
- cytokiny MeSH
- interferon gama MeSH
The aim of this study was to conduct QuantiFERON Monitor (QFM) testing in patients with multiple sclerosis (MS), which is used to monitor the state of the immune system through the non-specific stimulation of leukocytes followed by determining the level of interferon-gamma (IFN-γ) released from activated cells. Additionally, we tested the level of selected cytokines (IFN-α, IFN-γ, IL-1α, IL-1β, IL-1ra, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, IL-15, IL-33, VEGF) from stimulated blood samples to further understand the immune response. This study builds upon a previously published study, utilizing activated serum samples that were initially used for IFN-γ determination. However, our current focus shifts from IFN-γ to exploring other cytokines that could provide further insights into the immune response. A screening was conducted using Luminex technology, which yielded promising results. These results were then further elaborated upon using ELISA to provide a more detailed understanding of the cytokine profiles involved. This study, conducted from August 2019 to June 2023, included 280 participants: 98 RRMS patients treated with fingolimod (fMS), 96 untreated patients with progressive MS (pMS), and 86 healthy controls (HC). Our results include Violin plots showing elevated IL-1α in pMS and fMS. Statistical analysis indicated significant differences in the interleukin levels between groups, with IL-1ra and age as key predictors in differentiating HC from pMS and IL-1ra, IL-1α, age, and EDSS in distinguishing pMS from fMS. These findings suggest cytokines' potential as biomarkers in MS progression and treatment response.
Department of Neurology University Hospital Hradec Kralove 50005 Hradec Kralove Czech Republic
Faculty of Medicine in Hradec Králové Charles University 50003 Hradec Kralove Czech Republic
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Cohen J.A., Barkhof F., Comi G., Izquierdo G., Khatri B., Montalban X., Pelletier J., Eckert B., Häring D.A., Francis G. Fingolimod versus Intramuscular Interferon in Patient Subgroups from TRANSFORMS. J. Neurol. 2013;260:2023–2032. doi: 10.1007/s00415-013-6932-0. PubMed DOI PMC
Hemmer B., Kerschensteiner M., Korn T. Role of the Innate and Adaptive Immune Responses in the Course of Multiple Sclerosis. Lancet Neurol. 2015;14:406–419. doi: 10.1016/S1474-4422(14)70305-9. PubMed DOI
Wu X., Xue T., Wang Z., Chen Z., Zhang X., Zhang W., Wang Z. Different Doses of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front. Pharmacol. 2021;12:621856. doi: 10.3389/fphar.2021.621856. PubMed DOI PMC
Chang W.-T., Liu P.-Y., Wu S.-N. Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes. Molecules. 2020;25:4525. doi: 10.3390/molecules25194525. PubMed DOI PMC
Matloubian M., Lo C.G., Cinamon G., Lesneski M.J., Xu Y., Brinkmann V., Allende M.L., Proia R.L., Cyster J.G. Lymphocyte Egress from Thymus and Peripheral Lymphoid Organs Is Dependent on S1P Receptor 1. Nature. 2004;427:355–360. doi: 10.1038/nature02284. PubMed DOI
Brinkmann V., Davis M.D., Heise C.E., Albert R., Cottens S., Hof R., Bruns C., Prieschl E., Baumruker T., Hiestand P., et al. The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors. J. Biol. Chem. 2002;277:21453–21457. doi: 10.1074/jbc.C200176200. PubMed DOI
Wu Q., Wang Q., Mao G., Dowling C.A., Lundy S.K., Mao-Draayer Y. Dimethyl Fumarate Selectively Reduces Memory T Cells and Shifts the Balance between Th1/Th17 and Th2 in Multiple Sclerosis Patients. J. Immunol. 2017;198:3069–3080. doi: 10.4049/jimmunol.1601532. PubMed DOI PMC
Volpi C., Orabona C., Macchiarulo A., Bianchi R., Puccetti P., Grohmann U. Preclinical Discovery and Development of Fingolimod for the Treatment of Multiple Sclerosis. Expert Opin. Drug Discov. 2019;14:1199–1212. doi: 10.1080/17460441.2019.1646244. PubMed DOI
Miron V.E., Ludwin S.K., Darlington P.J., Jarjour A.A., Soliven B., Kennedy T.E., Antel J.P. Fingolimod (FTY720) Enhances Remyelination Following Demyelination of Organotypic Cerebellar Slices. Am. J. Pathol. 2010;176:2682–2694. doi: 10.2353/ajpath.2010.091234. PubMed DOI PMC
Sica F., Centonze D., Buttari F. Fingolimod Immune Effects Beyond Its Sequestration Ability. Neurol. Ther. 2019;8:231–240. doi: 10.1007/s40120-019-00162-7. PubMed DOI PMC
Mehling M., Brinkmann V., Antel J., Bar-Or A., Goebels N., Vedrine C., Kristofic C., Kuhle J., Lindberg R.L.P., Kappos L. FTY720 Therapy Exerts Differential Effects on T Cell Subsets in Multiple Sclerosis. Neurology. 2008;71:1261–1267. doi: 10.1212/01.wnl.0000327609.57688.ea. PubMed DOI
Grützke B., Hucke S., Gross C.C., Herold M.V.B., Posevitz-Fejfar A., Wildemann B.T., Kieseier B.C., Dehmel T., Wiendl H., Klotz L. Fingolimod Treatment Promotes Regulatory Phenotype and Function of B Cells. Ann. Clin. Transl. Neurol. 2015;2:119–130. doi: 10.1002/acn3.155. PubMed DOI PMC
Schwichtenberg S.C., Wisgalla A., Schroeder-Castagno M., Alvarez-González C., Schlickeiser S., Siebert N., Bellmann-Strobl J., Wernecke K.-D., Paul F., Dörr J., et al. Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells. Neurotherapeutics. 2021;18:1783–1797. doi: 10.1007/s13311-021-01078-7. PubMed DOI PMC
Idzko M., Hammad H., Nimwegen M.V., Kool M., Müller T., Soullié T., Willart M.A.M., Hijdra D., Hoogsteden H.C., Lambrecht B.N. Local Application of FTY720 to the Lung Abrogates Experimental Asthma by Altering Dendritic Cell Function. J. Clin. Investig. 2006;116:2935–2944. doi: 10.1172/JCI28295. PubMed DOI PMC
Cortese I., Reich D.S., Nath A. Progressive Multifocal Leukoencephalopathy and the Spectrum of JC Virus-Related Disease. Nat. Rev. Neurol. 2021;17:37–51. doi: 10.1038/s41582-020-00427-y. PubMed DOI PMC
Navikas V., Link H. Review: Cytokines and the Pathogenesis of Multiple Sclerosis. J. Neurosci. Res. 1996;45:322–333. doi: 10.1002/(SICI)1097-4547(19960815)45:4<322::AID-JNR1>3.0.CO;2-B. PubMed DOI
Gardiner B.J., Lee S.J., Cristiano Y., Levvey B.J., Sullivan L.C., Snell G.I., Peleg A.Y., Westall G.P. Evaluation of Quantiferon®-Monitor as a Biomarker of Immunosuppression and Predictor of Infection in Lung Transplant Recipients. Transpl. Infect. Dis. 2021;23:e13550. doi: 10.1111/tid.13550. PubMed DOI
Feng J.-Y., Ho L.-I., Chuang F.-Y., Pan S.-W., Chen Y.-Y., Tung C.-L., Li C.-P., Su W.-J. Depression and Recovery of IL-17A Secretion in Mitogen Responses in Patients with Active Tuberculosis-a Prospective Observational Study. J. Formos. Med. Assoc. 2021;120:1080–1089. doi: 10.1016/j.jfma.2020.09.012. PubMed DOI
Pavelek Z., Soucek O., Krejsek J., Sejkorova I., Vysata O., Klimová B., Angelucci F., Stourac P., Valis M., Peterka M., et al. Assessment of Functional Capacity of Immune System in Patients with Multiple Sclerosis Using QuantiFERON Monitor. J. Immunol. Res. 2023;2023:4653627. doi: 10.1155/2023/4653627. PubMed DOI PMC
Lublin F.D., Reingold S.C., National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis Defining the Clinical Course of Multiple Sclerosis: Results of an International Survey. Neurology. 1996;46:907–911. doi: 10.1212/WNL.46.4.907. PubMed DOI
Lublin F.D., Reingold S.C., Cohen J.A., Cutter G.R., Sørensen P.S., Thompson A.J., Wolinsky J.S., Balcer L.J., Banwell B., Barkhof F., et al. Defining the Clinical Course of Multiple Sclerosis: The 2013 Revisions. Neurology. 2014;83:278–286. doi: 10.1212/WNL.0000000000000560. PubMed DOI PMC
Virtanen P., Gommers R., Oliphant T.E., Haberland M., Reddy T., Cournapeau D., Burovski E., Peterson P., Weckesser W., Bright J., et al. SciPy 1.0: Fundamental Algorithms for Scientific Computing in Python. Nat. Methods. 2020;17:261–272. doi: 10.1038/s41592-019-0686-2. PubMed DOI PMC