Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains.

Autor:	Jacobs SAH; Department of Computer Science, Centre for Medical Image Computing, University College London, London, United Kingdom.; Department of Neurology, Imperial College Healthcare, London, United Kingdom., Muraro PA; Department of Neurology, Imperial College Healthcare, London, United Kingdom.; Division of Clinical Neurology, Department of Brain Sciences, Imperial College London, London, United Kingdom., Cencioni MT; Division of Clinical Neurology, Department of Brain Sciences, Imperial College London, London, United Kingdom., Knowles S; Department of Neurology, Imperial College Healthcare, London, United Kingdom., Cole JH; Department of Computer Science, Centre for Medical Image Computing, University College London, London, United Kingdom., Nicholas R; Department of Neurology, Imperial College Healthcare, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in neurology [Front Neurol] 2022 Jan 06; Vol. 12, pp. 801097. Date of Electronic Publication: 2022 Jan 06 (Print Publication: 2021).
DOI:	10.3389/fneur.2021.801097
Abstrakt:	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 ( AR 2 = 0.196), yet without improvement compared to brain-PAD alone ( AR 2 = 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. Competing Interests: JC is an advisor to and shareholder in BrainKey and Claristas HealthTech, and acts as a consultant to Queen Square Analytics. PM declares no conflicting interest relevant to this study, but discloses travel support and speaker honoraria from unrestricted educational activities organized by Novartis, Bayer HealthCare, Bayer Pharma, Biogen Idec, Merck-Serono and Sanofi Aventis; and consulting to Magenta Therapeutics and Jasper Therapeutics. RN has received funding for paid advisory boards with Roche, Novartis, Biogen and ImmunBio and has participated in trials run by Roche, Novartis and Biogen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Jacobs, Muraro, Cencioni, Knowles, Cole and Nicholas.)
Databáze:	MEDLINE
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