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J Autoimmun. 2016 Nov;74:208-216. doi: 10.1016/j.jaut.2016.07.002. Epub 2016 Jul 9.

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

Author information

1
Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy.
2
Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
3
Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani 2, 35123, Padova, Italy.
4
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) -Humanitas Clinical and Research Center, 20089, Milan, Italy.
5
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.
6
Division of Rheumatology, Department of Medicine, University of Padova, Via Giustiniani 2, 35123, Padova, Italy. Electronic address: adoria@unipd.it.

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.

KEYWORDS:

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

PMID:
27405845
DOI:
10.1016/j.jaut.2016.07.002
[Indexed for MEDLINE]

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