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Abstract: TH-PO0708

Effect of Steroid Therapy on Antinephrin Antibodies and B Lymphocytes in Minimal Change Disease: A Prospective Study

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Hengel, Felicitas E., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany
  • Beldi-Ferchiou, Asma, Institut Mondor de recherche biomedicale, Créteil, Île-de-France, France
  • Sakhi, Hamza, Institut Mondor de recherche biomedicale, Créteil, Île-de-France, France
  • Liaukouskaya, Nastassia, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany
  • Huber, Tobias B., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany
  • Ollero, Mario, Institut Mondor de recherche biomedicale, Créteil, Île-de-France, France
  • Tomas, Nicola M., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany
  • Audard, Vincent, Institut Mondor de recherche biomedicale, Créteil, Île-de-France, France
Background

The identification of autoantibodies against nephrin, a key signaling protein of the podocyte slit diaphragm, and their pathogenic role in patients with minimal change disease (MCD) has changed our understanding of primary podocytopathies. Details on underlying immune pathophysiolocal mechanisms such as the relation of anti-nephrin autoantibodies to immune cell subsets and therapy response remain to be determined.

Methods

This study was conducted as an ancillary study of biological sample collection to the prospective, multicenter, randomized, controlled trial “Rituximab from the first episode of Minimal Change Disease for preventing relapse risk in adult patients: a multicenter randomized controlled trial” (RIFIREINS: NCT0397057)”. Blood samples from adult patients with a de novo diagnosis of MCD were evaluated for the presence of anti-nephrin antibodies by immunoprecipitation as well as for B cell subpopulations by fluorescence-activated cell sorting at different time points (t0 at study initiation, t1 at 8 weeks after steroid treatment, t2 at 12 months of follow-up).

Results

We detected anti-nephrin antibodies in 12/17 (70.6%) therapy-naïve patients with MCD at study initiation (t0). All 12 (100%) patients positive for anti-nephrin antibodies achieved remission with no anti-nephrin antibodies detectable after 8 weeks of steroid treatment (t1). 2 out of 5 anti-nephrin negative patients did not reach clinical remission after 8 weeks of steroids (t1) and were excluded from the RIFIREINS study. The fraction of plasmablasts was higher in anti-nephrin positive than in anti-nephrin negative patients at study inclusion (t0), albeit not statistically significant. Plasmablasts and transitional B cells decreased while marginal zone-like B cells increased within 8 weeks of steroid treatment in anti-nephrin positive patients (t1), and B cellular subsets repopulated after 12 months of follow-up (t2).

Conclusion

In this prospective trial, anti-nephrin positive patients experienced remission in response to 8 weeks of steroid treatment, which associated with substantial changes of B cell subsets, indicating a therapeutically relevant effect of steroids on the B cell compartment within the time frame of clinical and serological remission.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)