An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26221753.
- Also identified by DOI 10.1038/ki.2015.233 and PMC identifier 4650264.
- Licence recorded as CC BY-NC-SA.
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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, FH<sup>1-5^18-20</sup>, using the unique factor H-deficient (Cfh-/-) mouse model of C3 glomerulopathy. FH<sup>1-5^18-20</sup> is comprised of the key complement regulatory domains (SCRs 1-5) linked to the surface recognition domains (SCRs 18-20). Intraperitoneal injection of FH<sup>1-5^18-20</sup> in 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, FH<sup>1-5^18-20</sup> is a potential therapeutic agent for C3 glomerulopathy and other renal conditions with alternative pathway-mediated tissue injury.