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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
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Multi-antibody composition in lupus nephritis: isotype and antigen specificity make the difference
Alice Bonanni1, Augusto Vaglio2, Maurizio Bruschi3
1Division of Nephrology, Dialysis, and Transplantation, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
Autoimmunity Reviews
|April 19, 2015
Summary
This study identifies specific autoantibodies in lupus nephritis kidney biopsies and serum, revealing novel diagnostic markers. These findings advance understanding of lupus nephritis pathogenesis and potential therapeutic targets.
Area of Science:
- Nephrology
- Immunology
- Proteomics
Background:
- Autoimmune glomerulonephritis research traditionally relied on animal models.
- Recent advancements in proteomics enable in vivo analysis of autoantibodies from human biopsies.
Purpose of the Study:
- To define renal autoimmune components in human lupus nephritis biopsies.
- To characterize autoantibody profiles in glomeruli and tubulointerstitial areas.
- To correlate renal autoantibodies with serum autoantibody profiles.
Main Methods:
- Laser microdissection and proteomics for in vivo autoantibody analysis.
- Laser capture of glomeruli and specific cells (CD38+, Ki-67+) from biopsies.
- Elution and characterization of renal antibodies using proteomics.
Main Results:
- Identified distinct autoantibody panels in glomeruli and tubulointerstitial areas.
- Major isotype IgG2 targeted novel podocyte proteins (αenolase, annexin AI) and known antigens (DNA, histone 3, C1q) in glomeruli.
- Vimentin identified as a tubulointerstitial antigen; serum autoantibody levels were significantly elevated in lupus nephritis patients.
Conclusions:
- Defined a unique autoimmune signature in lupus nephritis, differentiating it from other conditions.
- Targeted antigens are components of lupus NETosis, offering new insights into disease mechanisms.
- Correlating renal and serum autoantibodies refines understanding of lupus nephritis and potential clinical applications.
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