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Complement activation in IgA nephropathy.

R J Wyatt, Y Kanayama, B A Julian

    Kidney International
    |April 1, 1987
    PubMed
    Summary
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    Complement activation is frequently detected in IgA nephropathy patients. This study used a new assay to measure complement C3 activation in plasma, finding it present in over half of adult and pediatric patients.

    Area of Science:

    • Immunology
    • Nephrology
    • Complement System

    Background:

    • Alternative complement pathway activation is implicated in IgA nephropathy pathogenesis.
    • Glomerular deposition of C3 and properdin is common in IgA nephropathy.
    • Plasma C3 and C4 levels are typically normal or elevated, obscuring in vivo complement activation.

    Purpose of the Study:

    • To quantify C3 activation in plasma of IgA nephropathy patients using a novel assay.
    • To investigate the prevalence of C3 activation in pediatric and adult IgA nephropathy cohorts.
    • To explore potential associations between C3 activation and clinical parameters.

    Main Methods:

    • Quantification of in vivo C3 activation via a sensitive assay detecting the iC3b-C3d neoantigen.
    • Analysis of 202 plasma samples from 81 IgA nephropathy patients (pediatric and adult).

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  • Measurement of classical pathway activation using C4 levels.

    • Main Results:

    • Significantly increased iC3b-C3d neoantigen concentrations, indicating C3 activation, were found in 37% of pediatric and 57% of adult plasmas.
    • Serial testing revealed C3 activation in 75% of adult and 57% of pediatric patients at least once.
    • Classical pathway activation (C4) was detected in 20% of adult and 5% of pediatric plasmas.
    • No correlation was observed between elevated iC3b-C3d levels and macroscopic hematuria, renal insufficiency, or proteinuria.

    Conclusions:

    • Complement C3 activation is frequently detectable in the plasma of IgA nephropathy patients.
    • The novel iC3b-C3d neoantigen assay provides a sensitive method for detecting in vivo complement activation.
    • The precise pathophysiologic role of this plasma complement activation in IgA nephropathy requires further investigation.