An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy

作者：Nichols Eva Maria; Barbour Thomas D; Pappworth Isabel Y; Wong Edwin K S; Palmer Jeremy M; Sheerin Neil S; Pickering Matthew C; Marchbank Kevin J

来源：Kidney International, 2015, 88(6): 1314-1322.

DOI：10.1038/ki.2015.233

• C3 glomerulopathy
• factor H
• mini-FH
• therapeutic

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<^>18-20 is comprised of the key complement regulatory domains (SCRs 1-5) linked to the surface recognition domains (SCRs 18-20). Intraperitoneal injection of FH1-5<^>18-20 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, FH1-5<^>18-20 is a potential therapeutic agent for C3 glomerulopathy and other renal conditions with alternative pathway-mediated tissue injury.

• 出版日期2015-12