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Complement System01:27

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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
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Related Experiment Video

Updated: Feb 12, 2026

Treatment of Ligament Constructs with Exercise-conditioned Serum: A Translational Tissue Engineering Model
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An Engineered Complement Factor H Construct for Treatment of C3 Glomerulopathy.

Yi Yang1, Harriet Denton1, Owen R Davies2

  • 1Institute of Cellular Medicine, Newcastle University and National Renal Complement Therapeutics Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

Journal of the American Society of Nephrology : JASN
|March 29, 2018
PubMed
Summary

New mini-Factor H constructs show promise for treating C3 glomerulopathy. These engineered proteins demonstrate improved efficacy and longer serum half-life, offering potential new therapeutic options for complement-mediated diseases.

Keywords:
Immunology and pathologycomplementglomerulopathymembranoproliferative glomerulonephritis (MPGN)

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Area of Science:

  • Immunology
  • Nephrology
  • Biochemistry

Background:

  • C3 glomerulopathy (C3G) involves complement alternative pathway dysregulation, with limited treatment options.
  • Full-length Factor H (FH) is a potent regulator but difficult to produce.
  • Previous mini-FH constructs were effective but had short serum half-lives.

Purpose of the Study:

  • To develop improved mini-Factor H (FH) constructs with enhanced stability and efficacy.
  • To investigate the therapeutic potential of dimeric mini-FH variants for C3G.

Main Methods:

  • Engineered two homodimeric mini-FH constructs (FH R1-2^1-5^18-20 and FH 1-5^18-20^R1-2) by adding an oligomerization domain to a previously developed mini-FH.
  • Assessed construct binding, complement inhibition in vitro, and efficacy in FH-deficient mice.

Main Results:

  • Both dimeric constructs showed avid binding to C3b and superior inhibition of complement activity compared to native FH.
  • FH 1-5^18-20^R1-2 exhibited a >5-fold longer serum half-life and better kidney retention than the non-dimeric version.
  • FH 1-5^18-20^R1-2 significantly reduced glomerular C3 deposition in vivo.

Conclusions:

  • The dimeric mini-FH construct FH 1-5^18-20^R1-2 demonstrates enhanced stability and efficacy.
  • This construct holds potential as a therapeutic agent for C3G and other complement-mediated kidney diseases.