Universität zu Köln

Heesterbeek, Thomas J., Lechanteur, Yara T. E., Lores-Motta, Laura, Schick, Tina, Daha, Mohamed R., Altay, Lebriz, Liakopoulos, Sandra, Smailhodzic, Dzenita, den Hollander, Anneke, I, Hoyng, Carel B., de Jong, Eiko K. and Klevering, B. Jeroen (2020). Complement Activation Levels Are Related to Disease Stage in AMD. Invest. Ophthalmol. Vis. Sci., 61 (3). ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. To study the levels of complement activation in different disease stages of AMD and the influence of genetic polymorphisms in complement genes. METHODS. We included 797 patients with AMD and 945 controls from the European Genetic Database. Patients were grouped into five AMD stages: early AMD, intermediate AMD, central geographic atrophy, active choroidal neovascularization or inactive choroidal neovascularization. Differences in complement activation, as defined by the systemic C3d/C3 ratio, between AMD stages were evaluated using general linear modeling. In addition, we evaluated the influence of 18 genetic AMD polymorphisms in complement genes and their effect on complement activation. Differences in complement activation between stages were evaluated stratifying by complement associated haplotypes. RESULTS. Complement activation levels differed significantly between AMD disease stages. As compared with controls, the C3d/C3 ratio was higher in patients with intermediate AMD (P < 0.001) and central geographic atrophy (P = 0.001). Two polymorphisms in CFH (rs10922109 and rs570618) and one in CFB (rs116503776) were significantly associated with complement activation. The association between AMD disease stage and complement activation was more pronounced in patients with haplotypes associated with the highest complement activation. CONCLUSIONS. In general, consecutive AMD disease stages showed increasing levels of complement activation, especially in individuals with a genetic burden in complement genes. These findings contribute to the discussion on the pathogenesis of AMD in relation to complement activation and might suggest refinement in patient selection and the optimum window of treatment with complement inhibitors. Prospective studies are needed to confirm these results.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heesterbeek, Thomas J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lechanteur, Yara T. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lores-Motta, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Schick, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Daha, Mohamed R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altay, Lebriz UNSPECIFIED UNSPECIFIED UNSPECIFIED Liakopoulos, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Smailhodzic, Dzenita UNSPECIFIED UNSPECIFIED UNSPECIFIED den Hollander, Anneke, I UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Jong, Eiko K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klevering, B. Jeroen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-342461
DOI:	10.1167/iovs.61.3.18
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	61
Number:	3
Date:	2020
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MACULAR DEGENERATION; FACTOR-H; HIGH-RISK; ALTERNATIVE PATHWAY; RARE VARIANTS; PLASMA-LEVELS; C3; DRUSEN; ASSOCIATION; CFH Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34246