Systemic complement activation in age-related macular degeneration.

Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, paramete...

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Autores principales:	Hendrik P N Scholl, Peter Charbel Issa, Maja Walier, Stefanie Janzer, Beatrix Pollok-Kopp, Florian Börncke, Lars G Fritsche, Ngaihang V Chong, Rolf Fimmers, Thomas Wienker, Frank G Holz, Bernhard H F Weber, Martin Oppermann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54321e3b161340feb7ce15c45369cf16
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spelling	oai:doaj.org-article:54321e3b161340feb7ce15c45369cf162021-11-25T06:11:51ZSystemic complement activation in age-related macular degeneration.1932-620310.1371/journal.pone.0002593https://doaj.org/article/54321e3b161340feb7ce15c45369cf162008-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18596911/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related 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.Hendrik P N SchollPeter Charbel IssaMaja WalierStefanie JanzerBeatrix Pollok-KoppFlorian BörnckeLars G FritscheNgaihang V ChongRolf FimmersThomas WienkerFrank G HolzBernhard H F WeberMartin OppermannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 7, p e2593 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hendrik P N Scholl Peter Charbel Issa Maja Walier Stefanie Janzer Beatrix Pollok-Kopp Florian Börncke Lars G Fritsche Ngaihang V Chong Rolf Fimmers Thomas Wienker Frank G Holz Bernhard H F Weber Martin Oppermann Systemic complement activation in age-related macular degeneration.
description	Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related 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.
format	article
author	Hendrik P N Scholl Peter Charbel Issa Maja Walier Stefanie Janzer Beatrix Pollok-Kopp Florian Börncke Lars G Fritsche Ngaihang V Chong Rolf Fimmers Thomas Wienker Frank G Holz Bernhard H F Weber Martin Oppermann
author_facet	Hendrik P N Scholl Peter Charbel Issa Maja Walier Stefanie Janzer Beatrix Pollok-Kopp Florian Börncke Lars G Fritsche Ngaihang V Chong Rolf Fimmers Thomas Wienker Frank G Holz Bernhard H F Weber Martin Oppermann
author_sort	Hendrik P N Scholl
title	Systemic complement activation in age-related macular degeneration.
title_short	Systemic complement activation in age-related macular degeneration.
title_full	Systemic complement activation in age-related macular degeneration.
title_fullStr	Systemic complement activation in age-related macular degeneration.
title_full_unstemmed	Systemic complement activation in age-related macular degeneration.
title_sort	systemic complement activation in age-related macular degeneration.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/54321e3b161340feb7ce15c45369cf16
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Systemic complement activation in age-related macular degeneration.

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