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Related Concept Videos

Complement System01:27

Complement System

10.8K
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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Hypersensitivity Reactions: Cytolytic Reactions01:01

Hypersensitivity Reactions: Cytolytic Reactions

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Type II hypersensitivity involves IgG and IgM antibodies targeting cell surface antigens, leading to cell destruction. This can occur through complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), or acting as opsonins for phagocytosis. When excessive, these reactions cause significant tissue damage.Drug-induced hemolytic anemia is a common example, where drugs like penicillin or cephalosporins bind to red blood cells, forming drug-protein complexes. These complexes...
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Related Experiment Video

Updated: May 5, 2026

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells
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Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells

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C3d-Targeted factor H inhibits tissue complement in disease models and reduces glomerular injury without affecting

Fei Liu1, Sarah T Ryan1, Kelly C Fahnoe1

  • 1Q32 Bio, Waltham, MA 02451, USA.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|February 21, 2024
PubMed
Summary
This summary is machine-generated.

This study introduces targeted fusion proteins that inhibit complement locally, reducing disease activity in skin and kidney without systemic immunosuppression. This approach offers a safer, more effective treatment for complement-mediated diseases.

Keywords:
C3dcomplementfactor Hglomerular diseaseskin diseasetissue-targeted

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Area of Science:

  • Immunology
  • Biotechnology
  • Pharmacology

Background:

  • Systemic complement inhibitors face challenges with efficacy and infection risk due to abundant circulating complement.
  • Targeting complement locally offers a potential solution to overcome these limitations.

Purpose of the Study:

  • To develop and evaluate novel antibody fusion proteins for localized complement inhibition.
  • To assess the efficacy and safety of targeting tissue-bound complement components.

Main Methods:

  • Engineered antibody fusion proteins combining factor H (fH1-5) and an anti-C3d monoclonal antibody (C3d-mAb-2fH).
  • Validated protein binding to deposited complement in human skin and primate injury models.
  • Assessed tissue complement inhibition and disease modification in rodent models of skin injury and membranous nephropathy.

Main Results:

  • Fusion proteins demonstrated binding to deposited C3d in diseased skin and localized to activated complement in vivo.
  • Doses >1 mg/kg achieved >75% tissue complement inhibition in rodent models without systemic blockade.
  • Glomerular-specific inhibition reduced proteinuria and preserved kidney structure in a rat model.

Conclusions:

  • Targeting local tissue complement with C3d-mAb-2fH fusion proteins provides durable and effective blockade.
  • This localized approach avoids systemic inhibition, suggesting broad applicability for complement-mediated diseases.
  • The strategy offers a promising therapeutic avenue with reduced infection risk.