TY - JOUR
T1 - Immunization with pentraxin 3 (PTX3) leads to anti-PTX3 antibody production and delayed lupus-like nephritis in NZB/NZW F1 mice
AU - Gatto, Mariele
AU - Ghirardello, Anna
AU - Luisetto, Roberto
AU - Bassi, Nicola
AU - Fedrigo, Marny
AU - Valente, Marialuisa
AU - Valentino, Sonia
AU - Del Prete, Dorella
AU - Punzi, Leonardo
AU - Doria, Andrea
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - Anti-pentraxin 3 antibodies
KW - Complement activation
KW - Lupus glomerulonephritis
KW - Nephritogenic antibodies
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84992650271&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992650271&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2016.07.002
DO - 10.1016/j.jaut.2016.07.002
M3 - Article
AN - SCOPUS:84992650271
VL - 74
SP - 208
EP - 216
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
ER -