Kidney Week

Abstract: TH-OR94

Circulating Anti-nephrin Antibodies in Idiopathic Nephrotic Syndrome: A Large Cohort Study Testing Association with Disease Activity

Session Information

• Podocytopathies and Membranous Nephropathy: Clinical Advances
  October 24, 2024 | Location: Room 1, Convention Center
  Abstract Time: 05:00 PM - 05:10 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Angeletti, Andrea, Istituto Giannina Gaslini, Genova, Liguria, Italy

Andrea Angeletti, MD, PhD

• Spinelli, Sonia, Istituto Giannina Gaslini, Genova, Liguria, Italy

Sonia Spinelli, MSc, PhD

• Kajana, Xhuliana, Istituto Giannina Gaslini, Genova, Liguria, Italy

Xhuliana Kajana

• Caridi, Gianluca, Istituto Giannina Gaslini, Genova, Liguria, Italy

Gianluca Caridi, MBBS, MBChB

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

Paolo Cravedi, MD, PhD

• Lugani, Francesca, Istituto Giannina Gaslini, Genova, Liguria, Italy

Francesca Lugani, MD, PhD

• Bigatti, Carolina, Istituto Giannina Gaslini, Genova, Liguria, Italy

Carolina Bigatti, MD

• Ghiggeri, Gian Marco, Istituto Giannina Gaslini, Genova, Liguria, Italy

Gian Marco Ghiggeri, MD

• Bruschi, Maurizio, Istituto Giannina Gaslini, Genova, Liguria, Italy

Maurizio Bruschi, PhD

Background

Circulating anti-NEPHRIN antibodies (Abs) have been proposed as responsible for the disarrangement of the slit diaphragm in patients with idiopathic nephrotic syndrome (INS). However, available publications included limited cases and controls, focused on adults, and used multiple ELISAs for Abs detection, preventing comparisons across studies.

Methods

We included 156 INS patients with serum samples (396 samples), 32 kidney transplants with or not FSGS recurrence, and 143 controls. We also analyzed samples from an independent cohort of 47 INS enrolled in RCT (NCT02394119).
We compared the performance of the three ELISA assays used in previous studies, two targeting the extracellular domain (NEPHRIRIN-A and B), and the intracytoplasmic domain (C).

Results

Levels of Abs against extracellular domains (anti-NEPHRIN-A, aa 1-1055 and anti-NEPHRIN-B, aa 23-1029) correlate. In contrast, not with the cytoplasmic domain (Fig1A-B). Therefore, we show only the results relative to anti-NEPHRIN-A Abs.
Contrary to our prediction, we did not detect a significant difference in anti-NEPHRIN Abs between controls and INS patients, regardless of proteinuria (Fig1C). We identified 40ng/ml as the positivity threshold for our ELISA assay (Youden's index). Circulating anti-NEPHRIN Abs did not correlate with histology (Fig1D), nor FSGS recurrence after kidney transplant (Fig1E).
In 47 patients enrolled in RCT, anti-NEPHRIN-A Abs significantly decreased after treatment. However, when stratified based on relapse or not at 12 months of follow-up, serum levels at t_{6-9 months} were similar in relapsing and non-relapsing subjects (Fig1F).

Conclusion

Circulating anti-NEPHRIN Abs are present in a subset of INS patients and in kidney transplant recipients with FSGS recurrence, but they are not associated with disease activity. Our data are consistent with a potential pathogenic role of these antibodies, but they question their clinical utility in monitoring patients with INS.