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Kidney Week

Abstract: SA-PO937

Clinical Application of IgA-Type Autoantibodies Against Mesangial Autoantigen, βII-Spectrin, in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Nihei, Yoshihito, 1. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Iwasaki, Hiroyuki, 1. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Aoki, Ryousuke, 1. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Lee, Mingfeng, 1. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Hitoshi, 1. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Yusuke, 1. Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
Background

Half a century has passed since the first report of patients with IgA nephropathy (IgAN), however, the whole pathogenesis of IgAN remains elusive. In particular, the important question why IgA antibodies (Abs) are selectively deposited in the mesangial region, a hallmark of IgAN, remains unanswered. Recently, we have uncovered the answer to this critical question by identifying IgA type autoantibodies directed against mesangial autoantigen, βII-spectrin, in sera of patients with IgAN (Y. nihei et al. Science Advances 9, eadd6734, 2023). We confirmed that serum anti-βII-spectrin IgA was positive in 60% of patients with IgAN by Western blot. In present study, we aim to elucidate the specificity of serum levels of anti βII-spectrin in patients with IgAN and to clarify clinical aspects of serum anti βII-spectrin IgA.

Methods

To evaluate the specificity of anti-βII-spectrin IgA, serum anti-βII-spectrin IgA were measured by enzyme-linked immuno sorbent assay (ELISA) in patients with biopsy-proven IgAN (N=70) or other kidney diseases (N=32). The clinical parameters were compared between patients with IgAN who were positive for anti-βII-spectrin IgA and those who were negative. To test whether serum anti-βII-spectrin IgA titers correlate with disease activity, we compared the titers before and after steroid treatment in IgAN patients with positive for anti-βII-spectrin IgA.

Results

We found that 24 of 70 patients with IgAN have serum anti-βII-spectrin IgA while only two of 32 were positive for anti-βII-spectrin IgA in patients with other kidney diseases. No differences in eGFR, proteinuria, or histopathological findings were found between IgAN patients with positive and negative for serum anti-βII-spectrin IgA at the time of renal biopsy. The titer of anti-βII-spectrin IgA in patients with IgAN decreased after treatment with improvement in hematuria and proteinuria.

Conclusion

We found that anti-βII-spectrin IgA were detected in patients with IgAN with high specificity (specificity, 93.8%), suggesting that serum anti-βII-spectrin IgA may be useful for the diagnosis of IgAN. The decrease in serum anti-βII-spectrin IgA titers with improvement in hematuria and proteinuria after treatment indicated that serum anti-βII-spectrin IgA can be also used as a biomarker for monitoring disease activity.