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Human herpesvirus 6...
Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis
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- Grut, Viktor (author)
- Umeå University,Umeå universitet,Neurovetenskaper
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- Biström, Martin, 1982- (author)
- Umeå University,Umeå universitet,Neurovetenskaper
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- Salzer, Jonatan (author)
- Umeå University,Umeå universitet,Neurovetenskaper
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- Stridh, Pernilla (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Jons, Daniel (author)
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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- Gustafsson, Rasmus (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Fogdell-Hahn, Anna (author)
- Karolinska Institute,Karolinska University Hospital
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- Huang, Jesse (author)
- Karolinska Institute,Karolinska University Hospital
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- Butt, Julia (author)
- Infections and Cancer Epidemiology Division, German Cancer Research Center, Heidelberg, Germany
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- Lindam, Anna, PhD, 1978- (author)
- Umeå University,Umeå universitet,Institutionen för folkhälsa och klinisk medicin
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- Alonso-Magdalena, Lucia (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Stroke policy och kvalitetsregisterforskning,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Stroke policy and quality register research,Lund University Research Groups,Skåne University Hospital
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- Bergström, Tomas (author)
- Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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- Kockum, Ingrid (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Waterboer, Tim (author)
- Infections and Cancer Epidemiology Division, German Cancer Research Center, Heidelberg, Germany
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- Olsson, Tomas (author)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Zetterberg, Henrik (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Blennow, Kaj (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Andersen, Oluf (author)
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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- Nilsson, Staffan (author)
- Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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- Sundström, Peter (author)
- Umeå University,Umeå universitet,Neurovetenskaper
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(creator_code:org_t)
- Oxford University Press, 2024
- 2024
- English.
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In: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 147:1, s. 177-185
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Abstract
Subject headings
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- Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A.A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI).Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis).In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- axonal injury
- Epstein-Barr virus
- human herpesvirus 6-A
- multiple sclerosis
- neurofilament light chain
- axonal injury
- Epstein-Barr virus
- human herpesvirus 6-A
- multiple sclerosis
- neurofilament light chain
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Grut, Viktor
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Biström, Martin, ...
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Salzer, Jonatan
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Stridh, Pernilla
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Jons, Daniel
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Gustafsson, Rasm ...
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show more...
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Fogdell-Hahn, An ...
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Huang, Jesse
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Butt, Julia
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Lindam, Anna, Ph ...
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Alonso-Magdalena ...
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Bergström, Tomas
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Kockum, Ingrid
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Waterboer, Tim
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Olsson, Tomas
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Zetterberg, Henr ...
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Blennow, Kaj
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Andersen, Oluf
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Nilsson, Staffan
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Sundström, Peter
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Brain
- By the university
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Umeå University
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Lund University
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Karolinska Institutet
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University of Gothenburg