Multi-antibody composition in lupus nephritis: Isotype and antigen specificity make the difference

Alice Bonanni, Augusto Vaglio, Maurizio Bruschi, Renato Alberto Sinico, Lorenzo Cavagna, Gabriella Moroni, Franco Franceschini, Landino Allegri, Federico Pratesi, Paola Migliorini, Giovanni Candiano, Giampaola Pesce, Angelo Ravelli, Francesco Puppo, Alberto Martini, Angela Tincani, Gian Marco Ghiggeri

Research output: Contribution to journalArticle

Abstract

Research on autoimmune processes involved in glomerulonephritis has been for years based on experimental models. Recent progress in proteomics has radically modified perspectives: laser microdissection and proteomics were crucial for an in vivo analysis of autoantibodies eluted from human biopsies. Lupus nephritis has been the subject of recent independent researches.Main topics have been the definition of renal autoimmune components in human lupus biopsies; methods were laser capture of glomeruli and/or of single cells (CD38 + or Ki-67 +) from tubulointerstitial areas as starting step followed by elution and characterization of renal antibodies by proteomics.The innovative approach highlighted different panels of autoantibodies deposited in glomeruli and in tubulo-interstitial areas that actually represented the unique autoimmune components in these patients. IgG2 was the major isotype; new podocyte proteins (αenolase, annexin AI) and already known implanted molecules (DNA, histone 3, C1q) were their target antigens in glomeruli. Vimentin was the antigen in tubulo-interstitial areas.Matching renal autoantibodies with serum allowed the definition of a typical autoantibody serum map that included the same anti-αenolase, anti-annexin AI, anti-DNA, and anti-histone 3 IgG2 already detected in renal tissue. Serum levels of specific autoantibodies were tenfold increased in patients with lupus nephritis allowing a clear differentiation from both rheumatoid arthritis and other glomerulonephritis. In all cases, targeted antigens were characterized as components of lupus NETosis.Matching renal/serum autoantibody composition in vivo furnishes new insights on human lupus nephritis and allows to refine composition of circulating antibodies in patients with lupus. A thoughtful passage from bench to bedside of new knowledge would expand our clinical and therapeutic opportunities.

Original languageEnglish
Pages (from-to)692-702
Number of pages11
JournalAutoimmunity Reviews
Volume14
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

Keywords

  • Anti-annexin AI antibodies
  • Anti-DNA antibodies
  • Anti-αenolase antibodies
  • Autoimmunity
  • Lupus nephritis
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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    Bonanni, A., Vaglio, A., Bruschi, M., Sinico, R. A., Cavagna, L., Moroni, G., Franceschini, F., Allegri, L., Pratesi, F., Migliorini, P., Candiano, G., Pesce, G., Ravelli, A., Puppo, F., Martini, A., Tincani, A., & Ghiggeri, G. M. (2015). Multi-antibody composition in lupus nephritis: Isotype and antigen specificity make the difference. Autoimmunity Reviews, 14(8), 692-702. https://doi.org/10.1016/j.autrev.2015.04.004