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Glomerulonephritis with isolated C3 deposits and monoclonal gammopathy: a fortuitous association?

Abstract

BACKGROUND AND OBJECTIVES

Glomerular deposition of monoclonal Ig has been exceptionally described as the cause of membranoproliferative glomerulonephritis, through activation of the complement alternative pathway (CAP).

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

We retrospectively studied six adults with monoclonal gammopathy and glomerulonephritis (GN) characterized by isolated C3 deposits.

RESULTS

All patients presented with hematuria, associated with chronic renal failure and proteinuria in five patients, three of whom had nephrotic syndrome. Five patients had monoclonal gammopathy of undetermined significance and one had smoldering myeloma. The serum monoclonal IgG (κ four of six, λ two of six) was associated with light chain (LC) proteinuria in five patients. Four patients had low serum C3 and/or factor B levels. C4, factor H (CFH), and I protein levels were normal in five of five patients; none had detectable C3NeF. IgG anti-CFH activity was positive in one case. No mutations in CFH, CFI, and MCP genes were identified in four of four patients. Deposits were intramembranous, subepithelial, and mesangial by electron microscopy, and stained positive for C3 (six of six), properdin, and CFH (two of two) but negative for Ig LC and heavy chains, C4, and C1q (6/6) by immunofluorescence. Five patients progressed to end-stage renal disease over a median period of 47 months, despite chemotherapy in four patients. In one patient, monoclonal λLC deposits were observed on a follow-up kidney biopsy after 4 years.

CONCLUSIONS

GN with isolated glomerular C3 deposits might represent an unusual complication of plasma cell dyscrasia, related to complement activation through an autoantibody activity of the monoclonal Ig against a CAP regulator protein.

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  • Authors+Show Affiliations

    ,

    Department of Nephrology and Renal Transplantation, Hôpital Jean Bernard, 2, rue de la Milétrie, CHU Poitiers, 86021 Poitiers, France. f.bridoux@chu-poitiers.fr

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    MeSH

    Adult
    Aged
    Complement C3
    Complement Pathway, Alternative
    Female
    Follow-Up Studies
    Glomerulonephritis, Membranoproliferative
    Humans
    Male
    Middle Aged
    Paraproteinemias
    Retrospective Studies

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21784830