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Abstract: FR-PO683

Transplanted Immune Competent Bone Marrow or Spleen Stem Cells Prevent Myeloperoxidase (MPO)-ANCA Glomerulonephritis in Immune-Deficient Mice

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Hu, Peiqi, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Xiao, Hong, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Hu, Yanglin, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Gou, Shen-Ju, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Free, Meghan E., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Falk, Ronald, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Jennette, J. Charles, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Group or Team Name

  • UNC Kidney Center.
Background

ANCA disease patients cannot suppress the ANCA autoimmune response. Immune deficient Rag2 knock out (KO) mice also cannot suppress ANCA. We hypothesized that transplantation (Tx) of wild type (WT) bone marrow (BM) or spleen cells would provide Rag-2 KO mice with stem cells capable of defending against Tx of syngeneic MPO-ANCA B cells. This model could be used to identify specific stem cells for targeted therapy of autoimmune disease.

Methods

As previously described (Xiao H, et al. J Clin Invest 2002; 110:955-963), B6 Mpo knockout (KO) mice were immunized with mouse MPO and used as donors of splenocytes (SC) containing B-cells producing pathogenic MPO-ANCA. All B6 WT or B6 Rag2 KO mice received anti-MPO SC on day 0 (Table G1-8). G3,7 and 8 Rag2 KO mice also received normal WT B6 BM or SC Tx on day 0 (G6) or 2-6 weeks before anti-MPO SC Tx. Serum MPO-ANCA was measured on days 0, 4, 7, 11 and 14; and mice were euthanized on day 14 for pathology evaluation.

Results

No male (G1) or female (G4) WT mice developed MPO-ANCA or GN 14 d after injection of MPO-ANCA SC. All male (G2) and female (G5) Rag2 KO mice developed MPO-ANCA and GN by day 14. WT BM Tx into Rag2 KO mice 6 wks prior to anti-MPO SC (G3) prevented MPO-ANCA and GN. Similarly, Tx of WT SC 2 or 4 wks prior to MPO-ANCA SC (G7,G8) prevented MPO-ANCA and GN. However, Tx of WT SC on 0d (G6) did not prevent MPO-ANCA and GN.

Conclusion

Transplanted immune-competent stem cells from B6 WT BM or spleen prevent MPO-ANCA GN in Rag2 KO B6 syngeneic mice. Delay in developing autoimmune defense indicates that Tx stem cells require time to proliferate and differentiate to establish autoimmune defense (G6 vs G7 & G8). This model system will be used to identify specific stem cells that are effective in suppressing autoimmunity and effective for targeted immunotherapy.

Funding

  • NIDDK Support