A clinical study evaluating biomarkers of immunosenescence in the progression of age-related macular degeneration (the Immuno AMD Study)
A clinical study evaluating biomarkers of immunosenescence in the progression of age-related macular degeneration (the Immuno AMD Study)
Purpose : with increasing age, there is a general decline in regulatory elements of the immune system, termed immunosenescence. A clinical study was undertaken to test the hypothesis that systemic immunosenescence is an important etiological factor in AMD and drives disease progression.
Methods : sixty participants were recruited to this observational study, including ten age-matched control subjects. Participants with AMD had an identical stage of disease in both eyes (to investigate systemic immunosenescence), with ten participants in each of the following AMD categories: Early; intermediate; intermediate with reticular pseudodrusen (I-RPD), geographic atrophy and neovascular AMD. Proteomic analysis (discovery liquid mass chromatography) and immunophenotyping (8-colour flow cytometry) was undertaken on peripheral blood mononuclear cells (PBMCs) from each participant to identify biomarkers of immunosenescence. Proteomics and Mesoscale V-Plex assays were undertaken on plasma from each participant.
Results : for proteomic analysis, ANOVA testing was applied to each protein between all groups. Significant results were plotted, a pairwise comparison was undertaken to identify which differences were significant, and p-values were adjusted by the Bonferroni method. Proteomics revealed significant changes in PBMC protein levels between patients with early and intermediate (including I-RPD) stages of AMD and controls for the following proteins (associated gene): mitochondrial aspartate aminotransferase (GOT2), polyubiquitin B (UBB), cyclin-G associated kinase (GAK), transketolase (TKT) and isoamyl acetate-hydrolyzing esterase 1 homolog (IAH).
A stark result was the strongest reductions in protein levels in the I-RPD category, even relative to other AMD categories, for Derlin-1 (DERL1), mitochondrial NADH dehydrogenase subunit (NDUFB11) and an actin-related protein subunit (ARPC5L). Immunophenotyping demonstrated significant changes between groups in the CD57+KLRG1+ and CD57+ memory compartments of cytotoxic and helper T cells, in addition to the CD16+ (non-classical) monocyte and CD16+CD56low (cytotoxic) NK cell populations. Mesoscale assays did not show clear evidence of a circulating/systemic SASP between groups.
Conclusions : clinically-detectable biomarkers of immunosenescence could potentially be applied to AMD onset and progression pending validation on larger cohorts.
Khan, Adnan
97374057-d7e7-4849-ac94-c125ba1cc360
Shapanis, Andy
98b07884-92a9-4c00-afad-12194e339cbc
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
June 2024
Khan, Adnan
97374057-d7e7-4849-ac94-c125ba1cc360
Shapanis, Andy
98b07884-92a9-4c00-afad-12194e339cbc
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Khan, Adnan, Shapanis, Andy, Skipp, Paul and Lotery, Andrew
(2024)
A clinical study evaluating biomarkers of immunosenescence in the progression of age-related macular degeneration (the Immuno AMD Study).
Investigative Ophthalmology & Visual Science, 65 (7).
Record type:
Meeting abstract
Abstract
Purpose : with increasing age, there is a general decline in regulatory elements of the immune system, termed immunosenescence. A clinical study was undertaken to test the hypothesis that systemic immunosenescence is an important etiological factor in AMD and drives disease progression.
Methods : sixty participants were recruited to this observational study, including ten age-matched control subjects. Participants with AMD had an identical stage of disease in both eyes (to investigate systemic immunosenescence), with ten participants in each of the following AMD categories: Early; intermediate; intermediate with reticular pseudodrusen (I-RPD), geographic atrophy and neovascular AMD. Proteomic analysis (discovery liquid mass chromatography) and immunophenotyping (8-colour flow cytometry) was undertaken on peripheral blood mononuclear cells (PBMCs) from each participant to identify biomarkers of immunosenescence. Proteomics and Mesoscale V-Plex assays were undertaken on plasma from each participant.
Results : for proteomic analysis, ANOVA testing was applied to each protein between all groups. Significant results were plotted, a pairwise comparison was undertaken to identify which differences were significant, and p-values were adjusted by the Bonferroni method. Proteomics revealed significant changes in PBMC protein levels between patients with early and intermediate (including I-RPD) stages of AMD and controls for the following proteins (associated gene): mitochondrial aspartate aminotransferase (GOT2), polyubiquitin B (UBB), cyclin-G associated kinase (GAK), transketolase (TKT) and isoamyl acetate-hydrolyzing esterase 1 homolog (IAH).
A stark result was the strongest reductions in protein levels in the I-RPD category, even relative to other AMD categories, for Derlin-1 (DERL1), mitochondrial NADH dehydrogenase subunit (NDUFB11) and an actin-related protein subunit (ARPC5L). Immunophenotyping demonstrated significant changes between groups in the CD57+KLRG1+ and CD57+ memory compartments of cytotoxic and helper T cells, in addition to the CD16+ (non-classical) monocyte and CD16+CD56low (cytotoxic) NK cell populations. Mesoscale assays did not show clear evidence of a circulating/systemic SASP between groups.
Conclusions : clinically-detectable biomarkers of immunosenescence could potentially be applied to AMD onset and progression pending validation on larger cohorts.
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Published date: June 2024
Venue - Dates:
ARVO 2024 Annual Meeting, Seattle Convention Center - Arch Building, Seattle, United States, 2024-05-05 - 2024-05-09
Identifiers
Local EPrints ID: 494695
URI: http://eprints.soton.ac.uk/id/eprint/494695
ISSN: 0146-0404
PURE UUID: 884d8cf6-5579-42fd-bfcd-0eea1922564c
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Date deposited: 14 Oct 2024 16:40
Last modified: 15 Oct 2024 01:58
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