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Cerebrospinal fluid mtDNA concentrations are increased in multiple sclerosis and were normalized after intervention with autologous hematopoietic stem cell transplantation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Experimental neurology.ORCID iD: 0000-0002-7832-3083
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Experimental neurology.ORCID iD: 0000-0003-0934-4478
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Experimental neurology.ORCID iD: 0000-0001-7345-8256
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Experimental neurology.ORCID iD: 0000-0002-3385-6361
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2024 (English)In: Multiple Sclerosis and Related Disorders, ISSN 2211-0348, E-ISSN 2211-0356, Vol. 84, article id 105482Article in journal (Refereed) Published
Abstract [en]

Background

Mitochondrial 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.

Objectives

To verify elevated CSF mtDNA concentrations in MS patients and assess the impact of aHSCT on mtDNA concentrations.

Methods

Multiplex 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.

Results

CSF 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.

Conclusion

Our 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.

Place, publisher, year, edition, pages
Elsevier, 2024. Vol. 84, article id 105482
Keywords [en]
Mitochondrial DNA, Autologous hematopoietic stem cell, transplantation, Cerebrospinal fluid, Biomarkers, Multiple sclerosis, Droplet digital PCR
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-526178DOI: 10.1016/j.msard.2024.105482ISI: 001184482300001PubMedID: 38341978OAI: oai:DiVA.org:uu-526178DiVA, id: diva2:1850167
Funder
Swedish Research Council, 2021-02814Swedish Association of Persons with Neurological DisabilitiesInsamlingsfonden Bissen BrainwalkMarianne and Marcus Wallenberg FoundationSwedish Society for Medical Research (SSMF)Swedish Society of Medicine, SLS-726341Available from: 2024-04-09 Created: 2024-04-09 Last updated: 2024-04-09Bibliographically approved

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Pavlovic, IvanZjukovskaja, ChristinaHayat Nazir, FaisalMüller, MalinWiberg, AnnaBurman, Joachim
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Experimental neurologyDepartment of Immunology, Genetics and PathologyNeurology
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