Tags

Type your tag names separated by a space and hit enter

Systemic complement activation in age-related macular degeneration.
PLoS One. 2008 Jul 02; 3(7):e2593.Plos

Abstract

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.

Authors+Show Affiliations

Department of Ophthalmology, University of Bonn, Bonn, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18596911

Citation

Scholl, Hendrik P N., et al. "Systemic Complement Activation in Age-related Macular Degeneration." PloS One, vol. 3, no. 7, 2008, pp. e2593.
Scholl HP, Charbel Issa P, Walier M, et al. Systemic complement activation in age-related macular degeneration. PLoS One. 2008;3(7):e2593.
Scholl, H. P., 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., & Oppermann, M. (2008). Systemic complement activation in age-related macular degeneration. PloS One, 3(7), e2593. https://doi.org/10.1371/journal.pone.0002593
Scholl HP, et al. Systemic Complement Activation in Age-related Macular Degeneration. PLoS One. 2008 Jul 2;3(7):e2593. PubMed PMID: 18596911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systemic complement activation in age-related macular degeneration. AU - Scholl,Hendrik P N, AU - Charbel Issa,Peter, AU - Walier,Maja, AU - Janzer,Stefanie, AU - Pollok-Kopp,Beatrix, AU - Börncke,Florian, AU - Fritsche,Lars G, AU - Chong,Ngaihang V, AU - Fimmers,Rolf, AU - Wienker,Thomas, AU - Holz,Frank G, AU - Weber,Bernhard H F, AU - Oppermann,Martin, Y1 - 2008/07/02/ PY - 2008/03/12/received PY - 2008/05/31/accepted PY - 2008/7/4/pubmed PY - 2008/10/23/medline PY - 2008/7/4/entrez SP - e2593 EP - e2593 JF - PloS one JO - PLoS One VL - 3 IS - 7 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/18596911/Systemic_complement_activation_in_age_related_macular_degeneration_ L2 - https://dx.plos.org/10.1371/journal.pone.0002593 DB - PRIME DP - Unbound Medicine ER -