Glomerular Autoimmune Multicomponents of Human Lupus Nephritis In Vivo (2): Planted Antigens.
Glomerular planted antigens (histones, DNA, and C1q) are potential targets of autoimmunity in lupus nephritis (LN). However, the characterization of these antigens in human glomeruli in vivo remains inconsistent. We eluted glomerular autoantibodies recognizing planted antigens from laser-microdissected renal biopsy samples of 20 patients with LN. Prevalent antibody isotypes were defined, levels were determined, and glomerular colocalization was investigated. Renal and circulating antibodies were matched, and serum levels were compared in 104 patients with LN, 84 patients with SLE without LN, and 50 patients with rheumatoid arthritis (RA). Autoantibodies against podocyte antigens (anti-α-enolase/antiannexin AI) were also investigated. IgG2 autoantibodies against DNA, histones (H2A, H3, and H4), and C1q were detected in 50%, 55%, and 70% of biopsy samples, respectively. Anti-DNA IgG3 was the unique non-IgG2 anti-DNA deposit, and anti-C1q IgG4 was mainly detected in subepithelial membranous deposits. Anti-H3, anti-DNA, and anti-C1q IgG2 autoantibodies were also prevalent in LN serum, which also contained IgG3 against the antigen panel and anti-C1q IgG4. Serum and glomerular levels of autoantibodies were not strictly associated. High serum levels of all autoantibodies detected, including anti-α-enolase and antiannexin AI, identified LN versus SLE and RA. Anti-H3 and anti-α-enolase IgG2 levels had the most remarkable increase in LN serum and represented a discriminating feature of LN in principal component analysis. The highest levels of these two autoantibodies were also associated with proteinuria>3.5 g/24 hours and creatinine>1.2 mg/dl. Our findings suggest that timely autoantibody characterization might allow outcome prediction and targeted therapies for patients with nephritis.
Laboratory on Pathophysiology of Uremia and.
Maurizio
M
Bruschi
Departments of Clinical and Experimental Medicine and Italian Workers' Compensation Authority (INAIL) Research Center, University of Parma, Parma, Italy;
Maricla
M
Galetti
Division of Nephrology, Section of Clinical Immunology, San Carlo Hospital, Milan, Italy;
Renato Alberto
RA
Sinico
Division of Nephrology and Dialysis, Scientific Institute for Research and Health Care (IRCCS) Fondazione Ospedale Maggiore, Mangiagalli, Regina Elena, Milan, Italy;
Gabriella
G
Moroni
Divisions of Nephrology, Dialysis, and Transplantation and.
Alice
A
Bonanni
Division of Nephrology, Section of Clinical Immunology, San Carlo Hospital, Milan, Italy;
Antonella
A
Radice
Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy;
Angela
A
Tincani
Clinical Immunology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy;
Federico
F
Pratesi
Clinical Immunology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy;
Paola
P
Migliorini
Divisions of Nephrology, Dialysis, and Transplantation and.
Corrado
C
Murtas
Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy;
Franco
F
Franceschini
Division of Nephrology, Section of Clinical Immunology, San Carlo Hospital, Milan, Italy;
Barbara
B
Trezzi
Division of Nephrology, Section of Clinical Immunology, San Carlo Hospital, Milan, Italy;
Francesca
F
Brunini
Biomedical, Biotechnological and Translational Sciences and.
Rita
R
Gatti
Service of Pathological Anatomy, Division of Nephrology, Spedali Civili di Brescia, Brescia, Italy;
Regina
R
Tardanico
Divisions of Nephrology, Dialysis, and Transplantation and.
Giancarlo
G
Barbano
Divisions of Nephrology, Dialysis, and Transplantation and.
Giorgio
G
Piaggio
Division of Nephrology and Dialysis, Scientific Institute for Research and Health Care (IRCCS) Fondazione Ospedale Maggiore, Mangiagalli, Regina Elena, Milan, Italy;
Piergiorgio
P
Messa
Division of Nephrology, University of Calgary, Calgary, Alberta, Canada; and.
Pietro
P
Ravani
Division of Nephrology, University of Brescia, Montichiari Hospital, Brescia, Italy.
Francesco
F
Scolari
Laboratory on Pathophysiology of Uremia and.
Giovanni
G
Candiano
Paediatric Rheumatology, Scientific Institute for Research and Health Care (IRCCS), Istituto Giannina Gaslini, Genoa, Italy;
Alberto
A
Martini
Departments of Clinical and Experimental Medicine and.
Landino
L
Allegri
Laboratory on Pathophysiology of Uremia and Divisions of Nephrology, Dialysis, and Transplantation and GMarcoGhiggeri@ospedale-gaslini.ge.it.
Gian Marco
GM
Ghiggeri
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis*; D002460:Cell Line; D015922:Complement C1q / Q000276:immunology; D004247:DNA / Q000276:immunology; D005260:Female; D006657:Histones / Q000276:immunology; D006801:Humans; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; D006657:Histones; D015922:Complement C1q; D004247:DNA
SLE; clinical immunology; immunology and pathology; lupus nephritis