Kidney Week

Abstract: SA-PO615

Pneumococcal Polysaccharide Vaccine Regulates Murine Lupus

Session Information

• Glomerular Diseases: Immunology, Inflammation - II
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1202 Glomerular Diseases: Immunology and Inflammation

Authors

• Cantarelli, Chiara, Icahn School of Medicine at Mount Sinai, New York, United States

Chiara Cantarelli,

• Guglielmo, Chiara, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Chiara Guglielmo,

• Hartzell, Susan, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Susan Hartzell,

• Salem, Fadi, Mount Sinai Medical Center, New York, New York, United States

Fadi Salem,

• Andrighetto, Sofia, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Sofia Andrighetto,

• Fiaccadori, Enrico, Università di Parma, Parma, Italy

Enrico Fiaccadori,

• Tassiulas, Ioannis, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Ioannis Tassiulas,

• Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Paolo Cravedi,

Background

Current guidelines suggest the use of anti-pneumococcal vaccine Prevnar13 in patients with lupus, but the effects of such vaccination on disease severity are unknown.

Methods

We injected Prevnar13 (0.5 ml) or vehicle control into 8wk-old female MRL-lpr that spontaneously develop lupus. After 3mo, we measured circulating anti-PS IgG. In another set of animals, we quantified disease severity at 3 mo after Prevnar13 injection, including albuminuria, renal histology, and skin lesions. We also measured phenotype and function of splenocytes from treated and untreated mice, as well as renal STAT1 and STAT3 protein levels (WB).

Results

Prevnar13 induced the formation of anti-pneumococcal IgG (Fig. 1A). Prevnar13 treated animals showed less albuminuria, renal histological lesions, and milder dermatitis compared to controls (Fig. 1B-D). Improved disease severity in Prevnar13-treated animals was associated with reduced T follicular helper cells (T_FH) and more T follicular regulatory cells (Tfr) and regulatory T cells (Treg) (Fig. 1E). After aCD3/aCD28 stimulation, T lymphocytes from vaccinated mice showed less IL-17 and IL-4 production than non-vaccinated controls, while IL-10 production was significantly increased. Vaccinated mice had significantly decreased expression of STAT1 compared to controls, whereas STAT3 levels did not differ.

Conclusion

Anti-pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL-lpr mice, which associates with increased fewer T_FH and increased Tregs. These data strongly support the use of Prevnar vaccination in individuals with lupus.

Fig. 1. Anti-PS IgG in MRL-lpr mice at 3 months after Prevnar13 injection (A). Urinary albumin/creatinine ratio (ACR) at serial time points after vehicle control or Prevnar13 injection in MRL-lpr mice (B). Representative H&E staining and kidney (C) and skin (D) severity score at 3 months after injection. T_FH, Tfr, and Treg in the spleens of the same mice (E). *P < 0.05 vs. control at the same time-point.