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Abstract: FR-OR082

Modified Immune Cell (MIC) Therapy Ameliorates Murine Lupus Nephritis and Induces Regulatory B Cells In Vivo

Session Information

  • Lupus and Then Some
    November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
    Abstract Time: 04:42 PM - 04:54 PM

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Speer, Claudius, University Hospital Heidelberg, Heidelberg, BW, Germany
  • Kälble, Florian, University Hospital Heidelberg, Heidelberg, BW, Germany
  • Nusshag, Christian, University Hospital Heidelberg, Heidelberg, BW, Germany
  • Zeier, Martin G., University Hospital Heidelberg, Heidelberg, BW, Germany
  • Morath, Christian, University Hospital Heidelberg, Heidelberg, BW, Germany
  • Schaier, Matthias, University Hospital Heidelberg, Heidelberg, BW, Germany
Background

MICs are mononuclear cells that gain immunosuppressive properties after incubation with mitomycin C (MMC). We recently showed that syngeneic MIC therapy controlled experimental autoimmune encephalitis (EAE). In addition, allogeneic MICs prevented rejection in rat heart and hindlimb as well as pig kidney transplantation. We wanted to translate these encouraging findings to the prevention and treatment of lupus nephritis.

Methods

Splenocytes of syngeneic BWF1 donor mice were incubated with MMC and injected into recipient’s tail vein after matching for disease activity. Group 1 received no therapy, group 2 standard-dose MIC therapy with 1.5x108/kg BW and group 3 high-dose MIC therapy with 1.5x108/kg BW at week 1, 2 and 3. Group 4 received MIC infusions before disease onset as preemptive treatment approach. Disease activity was monitored by body weight, protein excretion, serum creatinine and dsDNA. Primary endpoint was day 40, protein excretion >3g/l and >20% loss of body weight. Kidney histopathology with PAS/HE staining was performed. Regulatory cell subsets and cytokine concentrations were measured.

Results

MIC therapy prevented the progression of lupus nephritis. Protein excretion, serum creatinine and dsDNA were lower in standard-dose and preemptive group compared to control group whereas repeated MIC therapy after disease onset had no effect. The endpoint was reached significantly more often in control group (67%) compared to groups 2 (14%), 3 (14%) and 4 (0%). Renal architecture was preserved in different MIC treatment groups with decreased glomerular and tubular damage scores. The frequency of CD5+CD1dhigh regulatory B cells was higher in MIC-treated compared to control animals, whereas double negative T cells were markedly reduced. IL-6 serum concentration was significantly decreased in group 2 and 4.

Conclusion

MIC therapy inhibits progression of active lupus nephritis. Preemptive MIC therapy delayed the onset of disease with no significant disease activity at completion of the study. In accordance with our EAE experiments and a first in-human clinical trial in kidney transplantation (TOL-1 study), MIC therapy was able to induce regulatory cell subsets in-vivo. This clinically applicable cell therapy may control lupus nephritis by specifically silencing deleterious autoimmune responses.

Funding

  • Commercial Support