Immunization with pentraxin 3 (PTX3) leads to anti-PTX3 antibody production and delayed lupus-like nephritis in NZB/NZW F1 mice. (November 2016)

• Record Type: Journal Article
• Authors: Gatto, Mariele; Ghirardello, Anna; Luisetto, Roberto; Bassi, Nicola; Fedrigo, Marny; Valente, Marialuisa; Valentino, Sonia; Del Prete, Dorella; Punzi, Leonardo; Doria, Andrea
• Is Part Of: Journal of autoimmunity. Volume 74(2016)
• Page Start: 208
• Page End: 216
• Publication Date: 2016-11
• Subjects: Anti-pentraxin 3 antibodies -- Lupus glomerulonephritis -- Complement activation -- Nephritogenic antibodies -- Survival; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2016.07.002
• Languages: English
• ISSNs: 0896-8411

Abstract

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. Highlights: Renal PTX3 deposition correlates with worse renal disease in lupus nephritis. Anti-PTX3 antibodies confirmed a protective role in murine lupus-like nephritis. Anti-PTX3 antibodies may hinder complement activation. IgG4 isotype may in part account for anti-PTX3 protective effect.