The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Complement factor H binds malondialdehyde epitopes and protects from oxidative stress
Open accessAbstract
Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.
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“Oxidative stress adducts and components of the complement system have been found to accumulate in drusen and sub-RPE deposits of patients with AMD (Weismann et al., 2011; Shaw et al., 2012), and mice with mutations making them prone to oxidative stress or dysregulation of the complement pathway have been presented as models of AMD (Imamura et al., 2006; Justilien et al., 2007; Hollyfield et al., 2”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Weismann et al., 2011
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Citations
Cites
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Complement factor H variant increases the risk of age-related macular degeneration
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Cited by
Sorted by citations
Items 501–533 of 533
Chakraborti, S., & Ram, S. (2018) · Springer eBooks · doi:10.1007/978-3-319-77674-3_4
Lamas-Basulto, E., Dersch, A. M., & Cortés, C. (2016) · Springer eBooks · doi:10.1007/978-1-4614-6438-9_101784-1
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Miyata, T. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737807033.793574103
Wu, X., Zhu, L., You, M., Chen, Y., Chai, H., Chen, L., Qian, Q., Shangguan, Z., Jiang, F., Li, S., et al. (2022) · Clinical Complementary Medicine and Pharmacology · doi:10.1016/j.ccmp.2022.100050
Brevnova, S. A. (2023) · International Journal of Veterinary Medicine · doi:10.52419/issn2072-2419.2023.2.213
Pathobiology of Non-neovascular Age-Related Macular Degeneration
Handa, J. T. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13820-1.00030-x
Miller, Y. I., & Tsimikas, S. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-28786-9.00007-4
Trockene altersabhängige Makuladegeneration
Liermann, Y. N., Thiele, S., & Holz, F. G. (2024) · Springer Reference Medizin · doi:10.1007/978-3-662-65929-8_50-1
Trockene altersabhängige Makuladegeneration
Liermann, Y. N., Thiele, S., & Holz, F. G. (2025) · Springer Reference Medizin · doi:10.1007/978-3-662-65823-9_50
Molecular, Cellular, and Animal Experiments in Formaldehyde Study
Fei, X., Wu, B., Qiang, M., Tong, Z., & He, R. (2025) · Springer eBooks · doi:10.1007/978-981-96-7281-3_16
Impact of Oxidized Lipids in the pathogenic mechanism of Age-Related Macular Degeneration
Angayarkanni, N., Babu, K. A., Raman, R., & Biswas, J. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-19116-9.00046-4
Tsai, K.-L., Chang, C.-C., Chang, Y.-S., Lu, Y.-Y., Tsai, I.-J., Chen, J.-H., Lin, S.-H., Tai, C.-C., Lin, Y.-F., Chang, H.-W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13889397
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gashti, R. Z., Karami, M., Habibi, E., Abbasi, A., Parsay, S., Modanloo, M., Khalili, H. A., & Shokrzadeh, M. (2025) · Research in Pharmaceutical Sciences · doi:10.4103/rps.rps_121_25
“MDA, a recognized indicator of oxidative stress, reflects excessive lipid peroxidation (61).”
Hacker, F., Roider, J. B., Klettner, A., & Dörschmann, P. (2026) · Marine Drugs · doi:10.3390/md24020064
“Alternatively, direct application of lipid peroxidation products might be employed in the future using prominent dry-AMD-related agents like malondialdehyde, isolevuglandins, or 7-ketocholesterol [30–32].”
Rôle du facteur H du complément et du récepteur CD47 dans l’inflammation sous-rétinienne
Augustin, S. (2021) · theses.fr (ABES) · doi:10.70675/be8ffdbez2125z4378za1bbzb8ba72c35267
Sannan, N. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2026.1776779
“Functional study showed that Y402H CFH exhibits reduced binding to oxidized lipids (like malondialdehyde epitopes), impairing protection of retinal cells from damage (Weismann et al., 2011).”
From urinalysis to photoacoustic imaging: A versatile probe for malondialdehyde in atherosclerosis
Shang, J., Yang, F., Hanbin, C., & Ma, Y. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110133
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“…we and others have shown that MDA-epitopes on apoptotic blebs and necrotic cells recruit regulators of the complement cascade, such as FH, complement factor H-related protein 1, 3 and 5 (FHR1, FHR3, and FHR5), but whether they directly activate complement cascades remains unclear (9, 11, 19, 20).”
InfluentialComplement Factor H‐Based Therapeutics: A Comprehensive Overview
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“Although these experiments were conducted with mouse nAbs against murine epitopes, human IgM nAbs against AMD and oxidative stress epitopes have been identified [ 123 ].”
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“4-HNE adduction to erythrocyte membrane proteins generates neo-antigenic epitopes that can be recognized by naturally occurring antibodies and complement components [102,103].”
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van Greevenbroek, M. M. J., & Trouw, L. A. (2026) · Immunological Reviews · doi:10.1111/imr.70166
“…MDA/AA neoepitopes has a major clinical impact as genetic variants in Factor H that are associated with age-related macular degeneration (AMD) impair the binding of Factor H to MDA/MAA modified proteins, thereby impacting on overall complement activation and complement-mediated phagocytosis [89].”
Castro-Fernández, D. C., Cañizo-Outeiriño, A., Martínez, A. L., Cuartero‐Martínez, A., Martinez, L. J. R., González‐Barcia, M., Fernández-Rodríguez, M. I., Rodríguez‐Cid, M. J., Abraldes, M. J., Almuiña-Varela, P., et al. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119361
Complement Factor H C-terminus and its significance : a structural narrative
Bhattacharjee, A. (2014) · Työväentutkimus Vuosikirja
Molecular investigations of age-related macular degeneration
Whitmore, S. S., Anderson, M. G., Sohn, E. H., Scheetz, T. E., Tan, K., & Mullins, R. F. (2015) · doi:10.17077/etd.7xzjf8nh
Metadata
- Authors
- Weismann, D., Hartvigsen, K., Lauer, N., Bennett, K. L., Scholl, H. P. N., Issa, P. C., Cano, M., Brandstätter, H., Tsimikas, S., Skerka, C., Superti-Furga, G., Handa, J. T., Zipfel, P. F., Witztum, J. L., & Binder, C. J.
- Affiliations
- Austrian Academy of Sciences (AT)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Johns Hopkins University (US)
- University of Oxford (GB)
- Octapharma (Austria) (AT)
- University of California San Diego (US)
- Corresponding author
- Binder, Christoph J.
- ORCID
- Venue
- Nature
- Published
- 2011-10
- Volume
- 478
- Issue
- 7367
- Pages
- 76-81
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4826616
- OpenAlex
- W2062097745
- Cited by
- 533
- References
- 42
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 25 · 2023: 30 · 2022: 29 · 2021: 42 · 2020: 36 · 2019: 29 · 2018: 33 · 2017: 31 · 2016: 39 · 2015: 42 · 2014: 44 · 2013: 66 · 2012: 44
- FWCI
- 22.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01-HL086599, HL-088093, P01HL088093)
- National Eye Institute (EY14005, R01EY014005, EY019044, R01EY019904)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- complement factor H, malondialdehyde, lipid peroxidation, oxidative stress, age-related macular degeneration, macrophage uptake, pro-inflammatory effects, innate immunity, chronic inflammation, retina
- MeSH terms
- Animals, Epitopes, Binding Sites, Complement System Proteins, Complement Inactivator Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Inflammation, Macular Degeneration, Male, Malondialdehyde, Mice, Inbred C57BL, Mutation, Necrosis, Protein Binding, Retina, Lipid Peroxidation, Apoptosis, Complement Factor H, Protein Structure, Tertiary, Macrophages, Peritoneal, Oxidative Stress, Mice
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