Immunization with Pentraxin3 prevents transition from subclinical to clinical lupus nephritis in lupus-prone mice: Insights from renal ultrastructural findings.
Animals
Antibody Formation
/ immunology
Antigen-Antibody Complex
/ ultrastructure
C-Reactive Protein
/ genetics
Complement System Proteins
/ metabolism
Disease Models, Animal
Disease Resistance
Female
Humans
Immunization
Kidney Glomerulus
/ metabolism
Lupus Nephritis
/ immunology
Mice
Mice, Inbred Strains
Microscopy, Electron
Serum Amyloid P-Component
/ genetics
Electron-dense deposits
Glomerular inflammation
Lupus nephritis
PTX3
Journal
Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
11
12
2019
revised:
15
03
2020
accepted:
22
03
2020
pubmed:
9
4
2020
medline:
31
8
2021
entrez:
9
4
2020
Statut:
ppublish
Résumé
Pentraxin3 (PTX3) is an emerging player in lupus nephritis (LN). Anti-PTX3 antibodies showed to delay LN occurrence in vivo. To evaluate renal changes following immunization with PTX3 in a murine model of LN. Twenty-two lupus-prone New Zealand Black/White (NZB/W)F1 mice were divided into two groups (n = 11) and subcutaneously injected with human recombinant (hr)PTX3 100 μg or phosphate buffer saline (PBS) 200 μl, three times 3 weeks apart, starting before development of proteinuria. Five mice from each group were scheduled for sacrifice at week 22 and 6 from each group at week 29. Renal lesions included electron-dense deposits (EDD), glomerular deposition of IgG, complement and PTX3 as markers of renal inflammation. They were evaluated by immunofluorescence (IF), confocal and immunoelectron microscopy (IEM). Validated semiquantitative scores were used when available to score renal lesions. Chi-squared test with Fisher exact test was used for comparison. Nineteen out of 22 mice were sacrificed as scheduled. Only hrPTX3-immunized mice developed anti-PTX3 antibodies. Compared to PBS-injected mice, they displayed a dramatic decrease in glomerular deposits of IgG, C1q and PTX3, as well as in the amount of EDD (p = 0.006) and podocyte effacement (p = 0.043). Importantly, PTX3 was pinpointed inside the EDD and co-localized with nuclear material. Immunization with PTX3 prevented progression from the preclinical to the clinical stage of LN, inciting anti-PTX3 antibodies and preventing renal PTX3 deposition. PTX3 is a novel component of EDD, submitting it as one initiating autoantigen in LN and as potential target for early treatment.
Sections du résumé
BACKGROUND
Pentraxin3 (PTX3) is an emerging player in lupus nephritis (LN). Anti-PTX3 antibodies showed to delay LN occurrence in vivo.
AIM
To evaluate renal changes following immunization with PTX3 in a murine model of LN.
MATERIALS AND METHODS
Twenty-two lupus-prone New Zealand Black/White (NZB/W)F1 mice were divided into two groups (n = 11) and subcutaneously injected with human recombinant (hr)PTX3 100 μg or phosphate buffer saline (PBS) 200 μl, three times 3 weeks apart, starting before development of proteinuria. Five mice from each group were scheduled for sacrifice at week 22 and 6 from each group at week 29. Renal lesions included electron-dense deposits (EDD), glomerular deposition of IgG, complement and PTX3 as markers of renal inflammation. They were evaluated by immunofluorescence (IF), confocal and immunoelectron microscopy (IEM). Validated semiquantitative scores were used when available to score renal lesions. Chi-squared test with Fisher exact test was used for comparison.
RESULTS
Nineteen out of 22 mice were sacrificed as scheduled. Only hrPTX3-immunized mice developed anti-PTX3 antibodies. Compared to PBS-injected mice, they displayed a dramatic decrease in glomerular deposits of IgG, C1q and PTX3, as well as in the amount of EDD (p = 0.006) and podocyte effacement (p = 0.043). Importantly, PTX3 was pinpointed inside the EDD and co-localized with nuclear material.
CONCLUSIONS
Immunization with PTX3 prevented progression from the preclinical to the clinical stage of LN, inciting anti-PTX3 antibodies and preventing renal PTX3 deposition. PTX3 is a novel component of EDD, submitting it as one initiating autoantigen in LN and as potential target for early treatment.
Identifiants
pubmed: 32265078
pii: S0896-8411(20)30056-1
doi: 10.1016/j.jaut.2020.102443
pii:
doi:
Substances chimiques
Antigen-Antibody Complex
0
Serum Amyloid P-Component
0
PTX3 protein
148591-49-5
Complement System Proteins
9007-36-7
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102443Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interests.