title: Immunization with pentraxin 3 (PTX3) leads to anti-PTX3 antibody production and delayed lupus-like nephritis in NZB/NZW F1 mice.
abstract: Anti-pentraxin 3 (PTX3) antibodies were associated with the absence of lupus glomerulonephritis in humans.
  
  
  
  To explore the effects of anti-PTX3 antibodies in New Zealand Black/White (NZB/NZW F1) mice and their inherent mechanisms of action.
  
  
  
  30 NZB/NZW F1 mice were subdivided into 3 groups of 10 mice each and subcutaneously injected with PTX3, alum and PBS (group 1), alum and PBS (group 2) or PBS alone (group 3), 3 times 3 weeks apart, before development of renal disease. Mice were followed until natural death. Histological analysis and immunohistochemistry were performed on harvested kidneys. Effects of anti-PTX3 antibodies on C1q binding to immobilized PTX3-anti-PTX3 immune complexes were evaluated in vitro using human SLE sera. Qualitative characterization of human IgG anti-PTX3 was performed.
  
  
  
  Only group 1 mice developed anti-PTX3 antibodies. Anti-dsDNA and anti-C1q antibodies appeared significantly later and at lower levels in group 1 mice vs. controls (p < 0.0001). Proteinuria-free and overall survival were significantly increased in group 1 mice vs. controls (p < 0.05 and p = 0.03, respectively). Histopathological analysis showed that glomerular and tubular PTX3 staining and renal lesions were increased in controls compared with immunized mice. Addition of human SLE sera positive for anti-PTX3 antibodies to C1q and fixed PTX3 interfered with C1q binding to PTX3-anti-PTX3 immune complexes. Qualitative characterization of human IgG anti-PTX3 showed an increased proportion of IgG4.
  
  
  
  Anti-PTX3 antibodies delay lupus-like nephritis and prolong survival of NZB/NZW F1 mice. In vitro observations suggest anti-PTX3 antibodies may dampen complement activation via their Fc fragment, likely hindering renal inflammation.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy.
authors.forename: Mariele
authors.initials: M
authors.lastname: Gatto
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ghirardello
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Luisetto
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bassi
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani 2, 35123, Padova, Italy.
authors.forename: Marny
authors.initials: M
authors.lastname: Fedrigo
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani 2, 35123, Padova, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) -Humanitas Clinical and Research Center, 20089, Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Valentino
authors.affiliation: Division of Nephrology, Department of Medicine DIMED, Laboratory of Histomorphology and Molecular Biology of the Kidney, University of Padua, Via Giustiniani 2, 35123, Padua, Italy.
authors.forename: Dorella
authors.initials: D
authors.lastname: Del Prete
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy. Electronic address: adoria@unipd.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D015415:Biomarkers; D001706:Biopsy; D002097:C-Reactive Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology; D015922:Complement C1q / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007150:Immunohistochemistry; D007677:Kidney Function Tests; D008181:Lupus Nephritis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D051379:Mice; D008814:Mice, Inbred NZB; D020011:Protective Agents; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D000099153:Pentraxins
chemical_list: D000893:Anti-Inflammatory Agents; D001323:Autoantibodies; D015415:Biomarkers; D002097:C-Reactive Protein; D015922:Complement C1q; D007074:Immunoglobulin G; D020011:Protective Agents; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: Anti-pentraxin 3 antibodies; Complement activation; Lupus glomerulonephritis; Nephritogenic antibodies; Survival