کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6161858 | 1249377 | 2015 | 9 صفحه PDF | دانلود رایگان |
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.
Journal: Kidney International - Volume 88, Issue 6, December 2015, Pages 1314-1322