Correction: Systemic Complement Activation in Age-Related Macular Degeneration
Open accessAbstract
Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of agerelated macular degeneration (AMD), the leading cause of blindness in the elderly.To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients.Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67).Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD.All activation products, especially markers of chronic complement activation Ba and C3d (p,0.001), were significantly elevated in AMD patients compared to controls.Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population.In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients.This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula.Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.
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Levels of circulating complement activation products may be associated with the severity of AMD.
“There is evidence suggesting that levels of circulating complement activation products may be associated with the severity of AMD”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [213]
Cites
DeLong, E. R., DeLong, D. M., & Clarke-Pearson, D. L. (1988) · Biometrics · doi:10.2307/2531595 · Cited by 22,649 · see citing works
Complement factor H polymorphism in age-related macular degeneration
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., et al. (2005) · Science · doi:10.1126/science.1109557 · Cited by 4,492 · see citing works
Causes and Prevalence of Visual Impairment Among Adults in the UnitedStates
(2004) · Archives of Ophthalmology · doi:10.1001/archopht.122.4.477 · Cited by 2,616 · see citing works
Complement factor H polymorphism and age-related macular degeneration
Edwards, A. O., Ritter, R., Abel, K. J., Manning, A., Panhuysen, C., & Farrer, L. A. (2005) · Science · doi:10.1126/science.1110189 · Cited by 2,449 · see citing works
Complement factor H variant increases the risk of age-related macular degeneration
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., et al. (2005) · Science · doi:10.1126/science.1110359 · Cited by 2,424 · see citing works
Purcell, S., Cherny, S. S., & Sham, P. C. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.1.149 · Cited by 2,057 · see citing works
Hageman, G. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(01)00010-6 · Cited by 1,265 · see citing works
The AMD Genetics Clinical Study Group, Gold, B., Merriam, J. E., Zernant, J., Hancox, L. S., Taiber, A. J., Gehrs, K., Cramer, K., Neel, J., Bergeron, J., et al. (2006) · Nature Genetics · doi:10.1038/ng1750 · Cited by 1,075 · see citing works
Complement C3 variant and the risk of age-related macular degeneration
Yates, J. R. W., Sepp, T., Matharu, B. K., Khan, J. C., Thurlby, D. A., Shahid, H., Clayton, D. G., Hayward, C., Morgan, J., Wright, A. F., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072618 · Cited by 829 · see citing works
Rivera, A., Fisher, S. A., Fritsche, L. G., Keilhauer, C. N., Lichtner, P., Meitinger, T., & Weber, B. H. F. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi353 · Cited by 788 · see citing works
Self-citationDrusen complement components C3a and C5a promote choroidal neovascularization
Nozaki, M., Raisler, B. J., Sakurai, E., Sarma, J. V., Barnum, S. R., Lambris, J. D., Chen, Y., Zhang, K., Ambati, B. K., Baffi, J. Z., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408835103 · Cited by 650 · see citing works
Holz, F. G., Bindewald-Wittich, A., Fleckenstein, M., Dreyhaupt, J., Scholl, H. P. N., & Schmitz-Valckenberg, S. (2007) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2006.11.041 · Cited by 619 · see citing works
Self-citationThe human complement factor H: functional roles, genetic variations and disease associations
de Córdoba, S. R., Esparza-Gordillo, J., GOICOECHEADEJORGE, E., López‐Trascasa, M., & Sánchez‐Corral, P. (2004) · Molecular Immunology · doi:10.1016/j.molimm.2004.02.005 · Cited by 572 · see citing works
Variation in complement factor 3 is associated with risk of age-related macular degeneration
Maller, J. B., Fagerness, J. A., Reynolds, R. C., Neale, B. M., Daly, M. J., & Seddon, J. M. (2007) · Nature Genetics · doi:10.1038/ng2131 · Cited by 437 · see citing works
Bora, P. S., Sohn, J.-H., Cruz, J. M. C., Jha, P., Nishihori, H., Wang, Y., Kaliappan, S., Kaplan, H. J., & Bora, N. S. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.1.491 · Cited by 249 · see citing works
Y402H polymorphism of complement factor H affects binding affinity to C-reactive protein
Laine, M., Jarva, H., Seitsonen, S., Haapasalo, K., Lehtinen, M. J., Lindeman, N., Anderson, D. H., Johnson, P. T., Järvelä, I., Jokiranta, T. S., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3831 · Cited by 246 · see citing works
Chong, N. H. V., Keonin, J., Luthert, P. J., Frennesson, C. I., Weingeist, D. M., Wolf, R. L., Mullins, R. F., & Hageman, G. S. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62248-1 · Cited by 218 · see citing works
Self-citationSpencer, K. L., Hauser, M. A., Olson, L. M., Schmidt, S., Scott, W. K., Gallins, P. J., Agarwal, A., Postel, E. A., Pericak‐Vance, M. A., & Haines, J. L. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm146 · Cited by 189 · see citing works
Clark, S. J., Higman, V. A., Mulloy, B., Perkins, S. J., Lea, S. M., Sim, R. B., & Day, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605083200 · Cited by 185 · see citing works
Mollnes, T. E., Garred, P., & Bergseth, G. (1988) · PubMed · Cited by 173 · see citing works
Complement analysis in the 21st century
Mollnes, T. E., Jokiranta, T. S., Truedsson, L., et al. (2007) · Molecular Immunology · doi:10.1016/j.molimm.2007.06.150 · Cited by 149 · see citing works
Estimation of Systemic Complement C3 Activity in Age-Related Macular Degeneration
Sivaprasad, S. (2007) · Archives of Ophthalmology · doi:10.1001/archopht.125.4.515 · Cited by 94 · see citing works
Inhibition of Terminal Complement Complex Formation and Cell Lysis by Monoclonal Antibodies
Würzner, R., Schulze, M., Happe, L., et al. (2017) · Complement and Inflammation · doi:10.1159/000463204 · Cited by 89 · see citing works
Complement activation in rheumatoid arthritis evaluated by C3dg and the terminal complement complex
Mollnes, T. E., Lea, T., Mellbye, O. J., et al. (1986) · Arthritis & Rheumatism · doi:10.1002/art.1780290603 · Cited by 74 · see citing works
Multiple Testing in the Context of Haplotype Analysis Revisited: Application to Case‐Control Data
Becker, T., Cichon, S., Jönson, E., & Knapp, M. (2005) · Annals of Human Genetics · doi:10.1111/j.1529-8817.2005.00198.x · Cited by 61 · see citing works
Scholl, H. P. N., Pető, T., Dandekar, S. S., Bunce, C., Xing, W., Jenkins, S. A., & Bird, A. C. (2003) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-002-0602-8 · Cited by 57 · see citing works
Self-citationElevated plasma levels of the immunosuppressive complement fragment Ba in renal failure
Oppermann, M., Kurts, C., Zierz, R., et al. (1991) · Kidney International · doi:10.1038/ki.1991.298 · Cited by 52 · see citing works
Self-citationOppermann, M., Baumgarten, H., Brandt, E. M., et al. (1990) · Journal of Immunological Methods · doi:10.1016/0022-1759(90)90358-3 · Cited by 47 · see citing works
Self-citationComitato, A., Spampanato, C., Chakarova, C. F., Sanges, D., Bhattacharya, S. S., & Marigo, V. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm118 · Cited by 44 · see citing works
Oppermann, M., Schulze, M. B., & Götze, O. (2017) · Complement and Inflammation · doi:10.1159/000463173 · Cited by 43 · see citing works
Self-citationScholl, H. P. N., Dandekar, S. S., Pető, T., et al. (2004) · Ophthalmology · doi:10.1016/j.ophtha.2003.05.003 · Cited by 33 · see citing works
Self-citationAssessment of complement activation in vivo
Oppermann, M., Höpken, U. E., & Götze, O. (1992) · Immunopharmacology · doi:10.1016/0162-3109(92)90018-8 · Cited by 30 · see citing works
Self-citationPERIPHERAL DRUSEN IN MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS TYPE II
Huang, S. J., COSTA, D. L. L., GROSS, N. E., et al. (2003) · Retina · doi:10.1097/00006982-200306000-00036 · Cited by 27 · see citing works
Bourke, B. E., Moss, I. K., Mumford, P., et al. (1982) · PubMed · Cited by 23 · see citing works
Branham, K. E. H., Liang, L., Swaroop, A., et al. (2021) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/zjak-x458 · Cited by 18 · see citing works
Defective complement control of factor H (Y402H) and FHL-1 in age-related macular degeneration
Skerka, C., Lauer, N., Keilhauer, C. N., et al. (2007) · Molecular Immunology · doi:10.1016/j.molimm.2007.06.018 · Cited by 16 · see citing works
Johnson, P. T., Betts, K. E., Radeke, M. J., et al. (2007) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2007.01.013 · Cited by 9 · see citing works
Age‐Related Macular Degeneration
Evans, J. (2005) · Evidence-Based Ophthalmology · doi:10.1002/9780470698709.ch36 · Cited by 3 · see citing works
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de Jong, S., Gagliardi, G., Garanto, A., de Breuk, A., Lechanteur, Y. T. E., Katti, S., van den Heuvel, L. P., Volokhina, E. B., & den Hollander, A. I. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100952 · Cited by 71 · see citing works
Hallam, T. M., Marchbank, K. J., Harris, C. L., Osmond, C., Shuttleworth, V. G., Griffiths, H., Cree, A. J., Kavanagh, D., & Lotery, A. J. (2020) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.61.6.18 · Cited by 57 · see citing works
Hammadi, S., Tzoumas, N., Ferrara, M., Meschede, I. P., Lo, K., Harris, C., Lako, M., & Steel, D. H. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082870 · Cited by 44 · see citing works
Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential
Stradiotto, E., Allegrini, D., Fossati, G., Raimondi, R., Sorrentino, T., Tripepi, D., Barone, G., Inforzato, A., & Romano, M. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113280 · Cited by 29 · see citing works
Complement Inhibition in Age-Related Macular Degeneration—Treat Early!
Scholl, H. P. N. (2022) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2021.6068 · Cited by 6 · see citing works
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- Authors
- Scholl, H. P. N., Charbel Issa, P., Walier, M., Janzer, S., Pollok-Kopp, B., Börncke, F., Fritsche, L. G., Chong, N. V., Fimmers, R., Wienker, T., Holz, F. G., Weber, B. H. F., & Oppermann, M.
- Affiliations
- University of Bonn (DE)
- University of Göttingen (DE)
- University of Regensburg (DE)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-07-11
- Volume
- 3
- Issue
- 7
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2651648
- OpenAlex
- W4240259803
- Cited by
- 39
- References
- 38
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 1
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Pro Retina-Stiftung
- European Commission
- Deutsche Forschungsgemeinschaft (LSHG-CT-2005-512036)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- age-related macular degeneration, alternative complement pathway, complement activation products, C3d, Bb, factor D, complement factor H, complement C3, single nucleotide polymorphisms, genetic susceptibility, plasma biomarkers
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