期刊
KIDNEY INTERNATIONAL
卷 88, 期 6, 页码 1314-1322出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2015.233
关键词
C3 glomerulopathy; factor H; mini-FH; therapeutic
资金
- Northern Counties Kidney Research Fund
- Kidney Research UK [RP32/1/2007, ST5/2009]
- Wellcome Trust Senior Fellowship in Clinical Science [098476]
- Kidney Research UK [TF12/2011, ST5/2009, RP7/2015] Funding Source: researchfish
- Medical Research Council [MR/K023519/1] Funding Source: researchfish
- MRC [MR/K023519/1] Funding Source: UKRI
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.
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