Article Text

Download PDFPDF

S7A:7 Administration of serpinb3 delays glomerulonephritis and attenuates the lupus-like disease in lupus murine models by an immunomodulatory effect
  1. M Gatto1,
  2. L Cavicchioli2,
  3. R Luisetto1,
  4. G Codolo3,
  5. G Maggioni1,
  6. F Saccon1,
  7. M Beggio1,
  8. P Pontisso4,
  9. A Ghirardello1 and
  10. A Doria1
  1. 1University of Padova – Unit of Rheumatology, Department of Medicine, Padova, Italy
  2. 2University of Padova – Department of Biomedicine and Nutrition, Padova, Italy
  3. 3University of Padova – General Pathology Unit, Department of Biology, Padova, Italy
  4. 4University of Padova – Department of Clinical and Experimental Medicine, Padova, Italy


Background Abnormal apoptosis and clearance of cellular debris concur to development of systemic lupus erythematosus (SLE). SERPINS (serin-protease inhibitors) are ancient molecules regulating immune homeostasis. SERPINB3 modulates apoptosis and is hypoexpressed on SLE B cells.

Aim To explore the effects of SERPINB3 administration in murine lupus models, focusing on glomerulonephritis.

Methods NZB/W F1 and MRL/lpr mice were used. 40 NZB/W F1 mice were divided into 4 groups of 10 mice each and intraperitoneally injected twice a week starting before occurrence of proteinuria traces (group 1 and 2, prophylactic approach) or after development of proteinuria 30 mg/dl (group 3 and 4, therapeutic approach) with hrSERPINB3 (7.5 µg/0.1 mL prophylactic approach, or 15 µg/0.1 mL therapeutic approach) or PBS (0.1 mL). 20 MRL/lpr mice were injected with hrSERPINB3 (group 5, n=10) or PBS (group 6, n=10) with a prophylactic approach. We assessed time of occurrence and titers of anti-dsDNA and anti-C1q antibodies by ELISA; proteinuria and serum creatinine; overall- and proteinuria-free survival. Six NZB/W F1 mice were sacrificed at week 27, while 10 MRL/lpr mice at week 13 and another 10 at 16/18 weeks for histological kidneys comparison. Flow-cytometry was performed on MRL/lpr splenocytes.

Non parametric tests were performed for statistics; proteinuria-free (<300 mg/dl) and overall survival were evaluated by Kaplan-Meier method.

Results Levels of autoantibodies were significantly decreased and delayed in group 1 vs group 2, group 3 vs group 4, and group 5 vs group 6 (p<0.0001 for all). Proteinuria levels were significantly reduced and proteinuria-free and overall survival were significantly improved in SERPINB3 groups vs controls (figure 1). No differences were found among creatinine serum levels. Histological analysis showed a lower prevalence of severe tubular lesions in group 5 vs group 6 MRL/lpr mice at week 16 (chi-squared p=0.014), and mice belonging to SERPINB3 groups showed a trend toward a reduced prevalence of severe glomerular and tubular lesions. Th17:Treg ratio significantly decreased due to a remarkable increase in Treg levels in MRL/lpr mice treated with SERPINB3.

Conclusions Administration of SERPINB3 significantly improves disease and delays the onset of severe glomerulonephritis in lupus-prone mice. SERPINB3 may influence immune-cell function through immunoregulatory effects involving promotion of Treg.

Abstract S7A:7 Figure 1

Survival in NZB/W F1 brought to natural death

  • lupus nephritis
  • serpins
  • regulatory T cells

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.