[HTML][HTML] An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy
EM Nichols, TD Barbour, IY Pappworth, EKS Wong… - Kidney international, 2015 - Elsevier
Kidney international, 2015•Elsevier
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 …
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 …
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.
Elsevier