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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2017 ; 28
(5
): 1462-1474
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English Wikipedia
Moss-Produced, Glycosylation-Optimized Human Factor H for Therapeutic Application
in Complement Disorders
#MMPMID27932477
Michelfelder S
; Parsons J
; Bohlender LL
; Hoernstein SNW
; Niederkrüger H
; Busch A
; Krieghoff N
; Koch J
; Fode B
; Schaaf A
; Frischmuth T
; Pohl M
; Zipfel PF
; Reski R
; Decker EL
; Häffner K
J Am Soc Nephrol
2017[May]; 28
(5
): 1462-1474
PMID27932477
show ga
Genetic defects in complement regulatory proteins can lead to severe renal
diseases, including atypical hemolytic uremic syndrome and C3 glomerulopathies,
and age-related macular degeneration. The majority of the mutations found in
patients with these diseases affect the glycoprotein complement factor H, the
main regulator of the alternative pathway of complement activation. Therapeutic
options are limited, and novel treatments, specifically those targeting
alternative pathway activation, are highly desirable. Substitution with
biologically active factor H could potentially treat a variety of diseases that
involve increased alternative pathway activation, but no therapeutic factor H is
commercially available. We recently reported the expression of full-length
recombinant factor H in moss (Physcomitrella patens). Here, we present the
production of an improved moss-derived recombinant human factor H devoid of
potentially immunogenic plant-specific sugar residues on protein N-glycans,
yielding approximately 1 mg purified moss-derived human factor H per liter of
initial P. patens culture after a multistep purification process. This
glycosylation-optimized factor H showed full in vitro complement regulatory
activity similar to that of plasma-derived factor H and efficiently blocked
LPS-induced alternative pathway activation and hemolysis induced by sera from
patients with atypical hemolytic uremic syndrome. Furthermore, injection of
moss-derived factor H reduced C3 deposition and increased serum C3 levels in a
murine model of C3 glomerulopathy. Thus, we consider moss-produced recombinant
human factor H a promising pharmaceutical product for therapeutic intervention in
patients suffering from complement dysregulation.
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