Age-related Macular Degeneration and Modification of Systemic Complement Factor H Production Through Liver Transplantation
Abstract
Purpose To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD). Design Multicenter, cross-sectional study. Participants We recruited 223 Western European patients ≥ 55 years old who had undergone LT ≥ 5 years previously. Methods We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor). Main outcome measures We evaluated AMD status and recipient and donor CFH Y402H genotype. Results In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100%…
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In a multicentre study of liver transplant patients, incident AMD was found to be associated with recipient, but not donor, CFH p.Y402H status.
“In a multicentre study of liver transplant patients, incident AMD was found to be associated with recipient, but not donor, CFH p.Y402H status”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [224]
Systemic complement production by the liver may not contribute to retinal disease.
“suggesting that systemic complement production by the liver may not contribute to retinal disease [224].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [224]
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- Authors
- Khandhadia, S., Hakobyan, S., Heng, L. Z., Gibson, J., Adams, D. H., Alexander, G. J., Gibson, J. M., Martin, K. R., Menon, G., Nash, K., Sivaprasad, S., Ennis, S., Cree, A. J., Morgan, B. P., & Lotery, A. J.
- Affiliations
- University of Southampton (GB)
- Cardiff University (GB)
- University College London (GB)
- Aston University (GB)
- NIHR Birmingham Liver Biomedical Research Unit (GB)
- University of Cambridge (GB)
- Frimley Park Hospital (GB)
- University Hospital Southampton NHS Foundation Trust (GB)
- King's College Hospital (GB)
- Corresponding author
- Lotery, Andrew J.
- ORCID
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 120
- Issue
- 8
- Pages
- 1612-1618
- ISSN
- 0161-6420 (ISSN-L)
- OpenAlex
- W2113502029
- Cited by
- 47
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 1 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 3
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Wellcome Trust (079249)
- National Institute for Health and Care Research (NF-SI-0512-10080)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- age-related macular degeneration, complement factor H, liver transplantation, C1 inhibitor
- MeSH terms
- Adult, Aged, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Genotype, Humans, Liver, Macular Degeneration, Male, Tissue Donors, Transplantation, Liver Transplantation, Complement Factor H, Polymorphism, Single Nucleotide, Genotyping Techniques
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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