title: Multi-antibody composition in lupus nephritis: isotype and antigen specificity make the difference.
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.
authors.affiliation: Division of Nephrology, Dialysis, and Transplantation, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bonanni
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.affiliation: Laboratory on Pathophysiology of Uremia, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.affiliation: Division of Nephrology and Section of Clinical Immunology, San Carlo Hospital, Milan, Italy.
authors.forename: Renato Alberto
authors.initials: RA
authors.lastname: Sinico
authors.affiliation: Division of Rheumatology, University and IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cavagna
authors.affiliation: Division of Nephrology and Dialysis, Scientific Institute for Research and Health Care (IRCCS), Regina Elena, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Moroni
authors.affiliation: Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Franceschini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, University of Pisa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Pratesi
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, University of Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.affiliation: Laboratory on Pathophysiology of Uremia, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.affiliation: Medical and Radiometabolic Therapy Unit, Department of Internal Medicine, University of Genoa, Italy.
authors.forename: Giampaola
authors.initials: G
authors.lastname: Pesce
authors.affiliation: Division of Paediatric Rheumatology, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Ravelli
authors.affiliation: Department of Internal Medicine, University of Genoa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Puppo
authors.affiliation: Division of Paediatric Rheumatology, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy. Electronic address: albertomartini@ospedale-gaslini.ge.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.affiliation: Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
authors.affiliation: Division of Nephrology, Dialysis, and Transplantation, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy; Laboratory on Pathophysiology of Uremia, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy. Electronic address: GMarcoGhiggeri@ospedale-gaslini.ge.it.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008181:Lupus Nephritis / Q000276:immunology*; D014746:Vimentin / Q000276:immunology
chemical_list: D000941:Antigens; D001323:Autoantibodies; D014746:Vimentin
keywords: Anti-DNA antibodies; Anti-annexin AI antibodies; Anti-αenolase antibodies; Autoimmunity; Lupus nephritis; Systemic lupus erythematosus