Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains
Background: Magnetic Resonance Imaging (MRI) analysis method “brain-age” paradigm could offer an intuitive prognostic metric (brain-predicted age difference: brain-PAD) for disability in Multiple Sclerosis (MS), reflecting structural brain health adjusted for aging. Equally, cellular senescence has...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.801097/full |
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| author | Sophie A. H. Jacobs Sophie A. H. Jacobs Paolo A. Muraro Paolo A. Muraro Maria T. Cencioni Sarah Knowles James H. Cole Richard Nicholas |
| author_facet | Sophie A. H. Jacobs Sophie A. H. Jacobs Paolo A. Muraro Paolo A. Muraro Maria T. Cencioni Sarah Knowles James H. Cole Richard Nicholas |
| author_sort | Sophie A. H. Jacobs |
| collection | DOAJ |
| description | Background: Magnetic Resonance Imaging (MRI) analysis method “brain-age” paradigm could offer an intuitive prognostic metric (brain-predicted age difference: brain-PAD) for disability in Multiple Sclerosis (MS), reflecting structural brain health adjusted for aging. Equally, cellular senescence has been reported in MS using T-cell biomarker CD8+CD57+.Objective: Here we explored links between MRI-derived brain-age and blood-derived cellular senescence. We examined the value of combining brain-PAD with CD8+CD57+(ILT2+PD-1+) T-cells when predicting disability score in MS and considered whether age-related biological mechanisms drive disability.Methods: Brain-age analysis was applied to T1-weighted MRI images. Disability was assessed and peripheral blood was examined for CD8+CD57+ T-cell phenotypes. Linear regression models were used, adjusted for sex, age and normalized brain volume.Results: We included 179 mainly relapsing-remitting MS patients. A high brain-PAD was associated with high physical disability (mean brain-PAD = +6.54 [5.12–7.95]). CD8+CD57+(ILT2+PD-1+) T-cell frequency was neither associated with disability nor with brain-PAD. Physical disability was predicted by the interaction between brain-PAD and CD8+CD57+ILT2+PD-1+ T-cell frequency (AR2 = 0.196), yet without improvement compared to brain-PAD alone (AR2 = 0.206; AICc = 1.8).Conclusion: Higher frequency of CD8+CD57+ILT2+PD-1+ T-cells in the peripheral blood in patients with an older appearing brain was associated with worse disability scores, suggesting a role of these cells in the development of disability in MS patients with poorer brain health. |
| first_indexed | 2024-04-11T20:29:24Z |
| format | Article |
| id | doaj.art-7ed8e2dbfab04bc69b99882a05a47409 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-11T20:29:24Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-7ed8e2dbfab04bc69b99882a05a474092022-12-22T04:04:33ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-01-011210.3389/fneur.2021.801097801097Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing BrainsSophie A. H. Jacobs0Sophie A. H. Jacobs1Paolo A. Muraro2Paolo A. Muraro3Maria T. Cencioni4Sarah Knowles5James H. Cole6Richard Nicholas7Department of Computer Science, Centre for Medical Image Computing, University College London, London, United KingdomDepartment of Neurology, Imperial College Healthcare, London, United KingdomDepartment of Neurology, Imperial College Healthcare, London, United KingdomDivision of Clinical Neurology, Department of Brain Sciences, Imperial College London, London, United KingdomDivision of Clinical Neurology, Department of Brain Sciences, Imperial College London, London, United KingdomDepartment of Neurology, Imperial College Healthcare, London, United KingdomDepartment of Computer Science, Centre for Medical Image Computing, University College London, London, United KingdomDepartment of Neurology, Imperial College Healthcare, London, United KingdomBackground: Magnetic Resonance Imaging (MRI) analysis method “brain-age” paradigm could offer an intuitive prognostic metric (brain-predicted age difference: brain-PAD) for disability in Multiple Sclerosis (MS), reflecting structural brain health adjusted for aging. Equally, cellular senescence has been reported in MS using T-cell biomarker CD8+CD57+.Objective: Here we explored links between MRI-derived brain-age and blood-derived cellular senescence. We examined the value of combining brain-PAD with CD8+CD57+(ILT2+PD-1+) T-cells when predicting disability score in MS and considered whether age-related biological mechanisms drive disability.Methods: Brain-age analysis was applied to T1-weighted MRI images. Disability was assessed and peripheral blood was examined for CD8+CD57+ T-cell phenotypes. Linear regression models were used, adjusted for sex, age and normalized brain volume.Results: We included 179 mainly relapsing-remitting MS patients. A high brain-PAD was associated with high physical disability (mean brain-PAD = +6.54 [5.12–7.95]). CD8+CD57+(ILT2+PD-1+) T-cell frequency was neither associated with disability nor with brain-PAD. Physical disability was predicted by the interaction between brain-PAD and CD8+CD57+ILT2+PD-1+ T-cell frequency (AR2 = 0.196), yet without improvement compared to brain-PAD alone (AR2 = 0.206; AICc = 1.8).Conclusion: Higher frequency of CD8+CD57+ILT2+PD-1+ T-cells in the peripheral blood in patients with an older appearing brain was associated with worse disability scores, suggesting a role of these cells in the development of disability in MS patients with poorer brain health.https://www.frontiersin.org/articles/10.3389/fneur.2021.801097/fullmultiple sclerosisbrain agebiomarkersimmunologyMRIatrophy |
| spellingShingle | Sophie A. H. Jacobs Sophie A. H. Jacobs Paolo A. Muraro Paolo A. Muraro Maria T. Cencioni Sarah Knowles James H. Cole Richard Nicholas Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains Frontiers in Neurology multiple sclerosis brain age biomarkers immunology MRI atrophy |
| title | Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains |
| title_full | Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains |
| title_fullStr | Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains |
| title_full_unstemmed | Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains |
| title_short | Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains |
| title_sort | worse physical disability is associated with the expression of pd 1 on inflammatory t cells in multiple sclerosis patients with older appearing brains |
| topic | multiple sclerosis brain age biomarkers immunology MRI atrophy |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.801097/full |
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