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Kidney Week

Abstract: SA-PO971

Anti-Nephrin Autoantibodies Broadly Detected in the General Population and in Non-Kidney Disease Patients

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Liu, Pan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Gallon, Lorenzo G., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Jin, Jing, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

Nephrin is the key structural component of the interpodocyte-spanning slit diaphragm, and mutations of NPHS1 are associated with congenital nephrotic syndrome. Recently, Watts and colleagues discovered anti-nephrin autoantibodies in patients with MCD (J Am Soc Nephrol. 2022 Jan;33:238-252.), suggesting these autoantibodies may be directly attributable to the etiology of podocytopathy and also might play a role in primary FSGS. With our own focus on FSGS, we collected plasma samples from kidney and non-kidney diseases and had them examined for anti-nephrin antibodies.

Methods

We tested a total of 126 plasma samples of recurrent vs nonrecurrent FSGS, primary and 2nd FSGS, MCD, MN, LN, IgAN, TX, T1D with no kidney involvement, and health controls (Fig). Anti-nephrin antibody titers were measured using ELISA coated with recombinant Nephrin extracellular domain (R&D Systems, Cat:9399-NN-050). In addition, we performed Western blotting (WB) analyses of the antisera against nephrin (C-FLAG tagged full-length nephrin from CHO cell transfection with plasmid).

Results

Based on an arbitrary cutoff, a majority of samples were negative for anti-nephrin antibodies, whereas between 5% and 38% of the patients were tested positive for the antibody with varying titers. However, positive antibodies were broadly detected across the spectrum of the disease types, with the highest titer from a nonrecurrent FSGS patient (post-renal transplant), and the highest percentage of antibody-positive cases in T1D. Consistently, high antibody titers detected by ELISA correlated well with high antibody signals in WB, confirming the robustness of our assays.

Conclusion

Admitting caveats, we were unable to find direct correlations between nephrin autoantibody titer and specific kidney or non-kidney disease types. Further studies are warranted to have a larger sample size, more balanced disease categories, and better methodologies for anti-nephrin autoantibody detection.