title: An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy.
abstract: Abnormal regulation of the complement alternative pathway is associated with C3 glomerulopathy. Complement factor H is the main plasma regulator of the alternative pathway and consists of 20 short consensus repeat (SCR) domains. Although recombinant full-length factor H represents a logical treatment for C3 glomerulopathy, its production has proved challenging. We and others have designed recombinant mini-factor H proteins in which 'non-essential' SCR domains have been removed. Here, we report the in vitro and in vivo effects of a mini-complement factor H protein, FH1-5^18-20, using the unique factor H-deficient (Cfh-/-) mouse model of C3 glomerulopathy. FH1-5^18-20is comprised of the key complement regulatory domains (SCRs 1-5) linked to the surface recognition domains (SCRs 18-20). Intraperitoneal injection of FH1-5^18-20in Cfh-/- mice reduced abnormal glomerular C3 deposition, similar to full-length factor H. Systemic effects on plasma alternative pathway control were comparatively modest, in association with a short half-life. Thus, FH1-5^18-20is a potential therapeutic agent for C3 glomerulopathy and other renal conditions with alternative pathway-mediated tissue injury.
authors.affiliation: Institutes of Cellular and Genetic Medicine, School of Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Nichols
authors.affiliation: Centre for Complement and Inflammation Research, Imperial College London, London, UK.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Barbour
authors.affiliation: Institutes of Cellular and Genetic Medicine, School of Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Isabel Y
authors.initials: IY
authors.lastname: Pappworth
authors.affiliation: Institutes of Cellular and Genetic Medicine, School of Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Edwin K S
authors.initials: EK
authors.lastname: Wong
authors.affiliation: Institutes of Cellular and Genetic Medicine, School of Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Palmer
authors.affiliation: Institutes of Cellular and Genetic Medicine, School of Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Neil S
authors.initials: NS
authors.lastname: Sheerin
authors.affiliation: Centre for Complement and Inflammation Research, Imperial College London, London, UK.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Pickering
authors.affiliation: Institutes of Cellular and Genetic Medicine, School of Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Marchbank