Immunization with pentraxin 3 (PTX3) leads to anti-PTX3 antibody production and delayed lupus-like nephritis in NZB/NZW F1 mice

Mariele Gatto, Anna Ghirardello, Roberto Luisetto, Nicola Bassi, Marny Fedrigo, Marialuisa Valente, Sonia Valentino, Dorella Del Prete, Leonardo Punzi, Andrea Doria

Research output: Contribution to journalArticle

Abstract

Background Anti-pentraxin 3 (PTX3) antibodies were associated with the absence of lupus glomerulonephritis in humans. Aim To explore the effects of anti-PTX3 antibodies in New Zealand Black/White (NZB/NZW F1) mice and their inherent mechanisms of action. Materials and methods 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. Results 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. Conclusions 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.

Original languageEnglish
Pages (from-to)208-216
Number of pages9
JournalJournal of Autoimmunity
Volume74
DOIs
Publication statusPublished - Nov 1 2016

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Keywords

  • Anti-pentraxin 3 antibodies
  • Complement activation
  • Lupus glomerulonephritis
  • Nephritogenic antibodies
  • Survival

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Gatto, M., Ghirardello, A., Luisetto, R., Bassi, N., Fedrigo, M., Valente, M., Valentino, S., Del Prete, D., Punzi, L., & Doria, A. (2016). Immunization with pentraxin 3 (PTX3) leads to anti-PTX3 antibody production and delayed lupus-like nephritis in NZB/NZW F1 mice. Journal of Autoimmunity, 74, 208-216. https://doi.org/10.1016/j.jaut.2016.07.002