27.

Systemic Complement Activation in Age-Related Macular
Degeneration

Hendrik P. N. Scholl¹, P. Charbel Issa¹, M. Walier²,
S. Janzer¹, F. Börncke³, L. G. Fritsche⁴, N.V. Chong⁵,
R. Fimmers², T. Wienker², F. G. Holz¹, B. H.F. Weber⁴,
M. Oppermann³
(¹Department of Ophthalmology, University of Bonn,
²Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn,
³Department of Cellular and Molecular Immunology, University of Göttingen,
⁴Institute of Human Genetics, University of Regensburg,
⁵Oxford Eye Hospital, University of Oxford)

Background: Dysregulation of the alternative pathway of complement (APC) cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. Methods: Parameters of systemic APC activation in blood plasma together with disease-associated genetic markers in AMD patients were determined. Plasma concentrations of complement activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and APC 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-complement component C2 gene (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. Results: All complement activation products, especially markers of chronic APC 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 that a model that is based only on APC activation markers Ba, C3d and
factor D has considerably better discriminative ability to identify AMD patients within our study population compared to a model based on known genetic markers of the complement system. In both the controls’ and AMD patients’ group, the protein
markers of APC activation were correlated with CFH haplotypes. Conclusion: This study is the first to show systemic complement activation in AMD patients and its association with genetic variants of CFH which were previously linked to AMD.

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