The story of complement factor I

Abstract

Factor I was first discovered in 1966. Its importance became apparent with the description of the original Factor I deficient patient in Boston in 1967. This patient presented with a hyperactive alternative complement pathway resulting in secondary complement deficiency due to continuous complement consumption. On the basis of these findings, the mechanism of the alternative pathway was worked out. In 1975, the surprise finding was made that elevating levels of Factor I in plasma down-regulated the alternative pathway. Attempts to exploit this finding for clinical use had a long and frustrating history and it was not until 2019 that the first patient was treated with the gene therapy vector for age related macular degeneration by Professor Sir Robert MacLaren in Oxford. This review follows the long and contorted course from initial observations to clinical use of complement Factor I.

Keywords: Age related degeneration; C3b breakdown cycle; C3b feedback cycle; Complement; Conglutinin; Factor I.