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P. Charbel Issa, H. P. N. Scholl, S. Janzer, F. Boernke, N. V. Chong, R. Fimmers, T. Wienker, F. G. Holz, B. H. F. Weber, M. Oppermann; Systemic Complement Activation in Patients With Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1357. doi: https://doi.org/.
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To detect alterations of marker proteins involved in the alternative complement pathway in patients with age-related macular degeneration (AMD).
112 AMD patients and 67 control subjects were analyzed for genetic polymorphisms in the complement factor H (CFH), factor B and complement component C2 (CFB-C2) and complement component C3 genes (see Abstract Scholl et al.). Plasma levels of substrates of the complement system (C3, C4, CFB), markers for acute complement activation (C3a, C5a), markers for chronic complement activation (C3d, Ba, C5b-9) and regulators of the complement system (CFH, factor D) were measured.
Plasma concentration of CFH did not differ between the AMD patient group and the control group (median AMD, 546 µg/ml [5th, 95th percentiles: 396, 758]; median controls, 515 µg/ml [365, 711]; p=0.21). This was also true for the complement substrates C3 (AMD, 1.12 g/l [0.89, 1.53]; controls, 1.19 g/l [0.85, 1.48]; p=1.0) and C4 (AMD, 0.23 g/l [0.15, 0.38]; controls, 0.24 g/l [0.15, 0.34]; p=1.0). CFB was increased in the AMD population (AMD, 803 µg/ml [497, 1489]; controls, 642 µg/ml [378, 1354]; p=0.02) as was factor D (AMD, 1.27 µg/ml [0.69, 2.30];controls, 0.95 µg/ml [0.50, 1,65]; p < 0.001). The AMD group showed a significant increase of protein markers for acute complement activation, C3a (AMD, 15.5 ng/ml [11.2, 24.1]; controls, 14.3 ng/ml [10.6, 21.2]; p=0.03) and C5a (AMD, 1.85 ng/ml [0.78, 2.66], controls, 1.67 ng/ml [0.66, 2.32]; p=0.04) and for chronic complement activation, C3d (AMD, 55.2 ng/ml [33.7, 94.1]; controls, 46.9 ng/ml [32.2, 68.5]; p<0.001), Ba (AMD, 1.33 µg/ml [0.90, 2.09]; controls, 1.09 µg/ml [0.60, 1.71]; p<0.001) and SC5b-9 (AMD, 188 units [107, 777]; controls, 159 units [90, 710]; p=0.01).
AMD patients exhibit a systemic alteration of proteins involved in the alternative complement cascade. The strongest effect was observed for factor D, Ba and C3d. This study supports a major role of inflammation in the pathogenesis of AMD, specifically of the alternative complement pathway.
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