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Lookup NU author(s): Dr Thomas Hallam, Anneliza Andreadi, Professor David KavanaghORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Complement factor I (FI) is the nexus for classical, lectin and alternative pathwaycomplement regulation. FI is an 88kDa plasma protein that circulates in an inactiveconfiguration until it forms a trimolecular complex with its cofactor and substratewhereupon a structural reorganization allows the catalytic triad to cleave its substrates,C3b and C4b. In keeping with its role as the master complement regulatory enzyme,deficiency has been linked to immunopathology. In the setting of complete FIdeficiency, a consumptive C3 deficiency results in recurrent infections withencapsulated microorganisms. Aseptic cerebral inflammation and vasculiticpresentations are also less commonly observed. Heterozygous mutations in the factor Igene (CFI) have been demonstrated to be enriched in atypical haemolytic uraemicsyndrome, albeit with a very low penetrance. Haploinsufficiency of CFI has also beenassociated with decreased retinal thickness and is a strong risk factor for thedevelopment of age-related macular degeneration.Supplementation of complement FI using plasma purified or recombinant protein haslong been postulated, however, technical difficulties prevented progression into clinicaltrials. It is only using gene therapy that CFI supplementation has reached the clinic withGT005 in phase I/II clinical trials for geographic atrophy.
Author(s): Hallam T, Sharp S, Andreadi A, Kavanagh D
Publication type: Article
Publication status: Published
Journal: Immunobiology
Year: 2023
Volume: 228
Issue: 5
Print publication date: 01/09/2023
Online publication date: 05/06/2023
Acceptance date: 01/06/2023
Date deposited: 14/07/2023
ISSN (print): 0171-2985
ISSN (electronic): 1878-3279
Publisher: Elsevier GmbH
URL: https://doi.org/10.1016/j.imbio.2023.152410
DOI: 10.1016/j.imbio.2023.152410
Data Access Statement: No data was used for the research described in the article.
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