Immunization with Pentraxin3 prevents transition from subclinical to clinical lupus nephritis in lupus-prone mice: insights from renal ultrastructural findings
| Autor: | Roberto Luisetto, Laura Cavicchioli, Davide Trez, Federico Bonsembiante, Paolo Simioni, Mariele Gatto, Andrea Doria, Anna Ghirardello, Sonia Valentino, Claudia M. Radu, Barbara Bottazzi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Immunoelectron microscopy Glomerular deposits Immunology Kidney Glomerulus Lupus nephritis Mice Inbred Strains Antigen-Antibody Complex Immunofluorescence 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Animals Humans Subclinical infection Disease Resistance 030203 arthritis & rheumatology Proteinuria Systemic lupus erythematosus biology medicine.diagnostic_test business.industry Complement System Proteins medicine.disease Lupus Nephritis Disease Models Animal Microscopy Electron Serum Amyloid P-Component 030104 developmental biology C-Reactive Protein Antibody Formation biology.protein Female Immunization medicine.symptom Antibody business |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|