ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: TH-PO0426

Post-Rituximab Relapse Is Associated with Antinephrin Memory B Cells in Pediatric Patients with Idiopathic Nephrotic Syndrome

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Colucci, Manuela, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Riganati, Martina, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Zotta, Federica, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Gargiulo, Antonio, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Angeletti, Andrea, Istituto Giannina Gaslini, Genoa, Liguria, Italy
  • Caridi, Gianluca, Istituto Giannina Gaslini, Genoa, Liguria, Italy
  • Kajana, Xhuliana, Istituto Giannina Gaslini, Genoa, Liguria, Italy
  • Emma, Francesco, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
  • Vivarelli, Marina, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Lazio, Italy
Background

The efficacy of B-cell-depleting agents such as rituximab (RTX) and the identification of anti-nephrin autoantibodies support a key role of B cells in the pathogenesis of idiopathic nephrotic syndrome (INS). Memory B cells have been also implicated, serving as predictors of recurrence. However, the duration of drug-free remission after RTX treatment varies widely, and current anti-nephrin autoantibody detection methods are technically complex.

Methods

This study investigated whether the presence of anti-nephrin-specific memory B cells is associated with post-RTX relapse in pediatric INS. We included 13 children treated with RTX, classified as relapsing (n=9) or non-relapsing (n=4) during a 24-month follow-up. Controls with non–immune-mediated renal diseases (n=10) were also enrolled. Total and anti-nephrin-specific IgG-producing memory B cells were quantified using a novel Fluorospot assay developed in our laboratory at baseline and at last follow-up (defined as 24 months for non-relapsers and at relapse/repeated RTX infusion for relapsers).

Results

Median total IgG-producing memory B-cell counts were significantly reduced in INS patients prior to RTX treatment compared to controls, likely due to immunosuppressive drugs administered at baseline. In contrast, anti-nephrin IgG-producing memory B-cell levels were significantly higher in INS patients than in controls. In the relapsing group, recurrence occurred after a mean of 15.8 ± 8.0 months. Median total IgG-producing memory B-cell counts were comparable between relapsing and non-relapsing patients at baseline (p=0.6) and at last follow-up (p=0.2). However, anti-nephrin IgG-producing memory B-cell levels, initially similar in both groups (p=0.74), significantly increased at last follow-up in relapsers (p=0.03) but were completely absent in all non-relapsing patients (p=0.01 vs. relapsers).
These findings suggest that RTX effectively and durably depletes anti-nephrin-specific memory B cells in patients who achieve sustained remission, whereas these cells persist or re-emerge in those who relapse.

Conclusion

The novel Fluorospot assay developed in our laboratory enables efficient enumeration of anti-nephrin memory B cells, which may help identify pediatric INS patients at risk of relapse following RTX treatment. Further studies are needed to assess its predictive value in identifying relapse risk before clinical recurrence.