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Related Experiment Videos

Human IgA activates the complement system via the mannan-binding lectin pathway.

A Roos1, L H Bouwman, D J van Gijlswijk-Janssen

  • 1Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. A.Roos@LUMC.NL

Journal of Immunology (Baltimore, Md. : 1950)
|August 18, 2001
PubMed
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Mannan-binding lectin (MBL) binds to immunoglobulin A (IgA), activating the complement system. This interaction enhances innate immunity and may explain IgA nephropathy.

Area of Science:

  • Immunology
  • Innate Immunity
  • Complement System

Background:

  • The lectin pathway, initiated by mannan-binding lectin (MBL), is crucial for innate immunity.
  • MBL deficiency increases susceptibility to infections, particularly mucosal infections.
  • Immunoglobulin A (IgA) is a key mediator of mucosal immunity.

Purpose of the Study:

  • To investigate if IgA activates the complement system via the MBL-initiated lectin pathway.
  • To explore the mechanism of MBL-IgA interaction and its functional consequences.

Main Methods:

  • Dose-dependent MBL binding assays to immobilized IgA.
  • Calcium dependency and inhibition studies using mannose and anti-MBL antibodies.
  • Complement activation assays measuring C4 and C3 deposition.

Related Experiment Videos

  • Analysis of MBL-deficient and wild-type serum for IgA-induced complement activation.
  • Main Results:

    • MBL binds dose-dependently to polymeric IgA, involving its carbohydrate recognition domain.
    • MBL binding to IgA triggers complement activation (C4 and C3 deposition) at physiologically relevant concentrations.
    • Serum from MBL-deficient individuals shows reduced IgA-induced complement activation compared to wild-type.

    Conclusions:

    • MBL binding to IgA activates the complement system, suggesting a synergistic role in antimicrobial defense.
    • This interaction may enhance mucosal immunity and contribute to the pathogenesis of IgA nephropathy.