Kidney Week

Abstract: TH-OR95

Co-localization of IgG with Nephrin in Immune-Mediated Idiopathic Nephrotic Syndrome

Session Information

• Podocytopathies and Membranous Nephropathy: Clinical Advances
  October 24, 2024 | Location: Room 1, Convention Center
  Abstract Time: 05:10 PM - 05:20 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Inoki, Yuta, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Yuta Inoki, MD

• Ichikawa, Yuta, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Yuta Ichikawa

• Sakakibara, Nana, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Nana Sakakibara, MD, PhD

• Kimura, Yuka, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Yuka Kimura

• Tanaka, Yu, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Yu Tanaka, MD

• Ueda, Chika, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Chika Ueda, MD

• Kitakado, Hideaki, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Hideaki Kitakado, MD

• Nagano, China, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

China Nagano, MD, PhD

• Ishimori, Shingo, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Shingo Ishimori, MD, PhD

• Horinouchi, Tomoko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Tomoko Horinouchi, MD, PhD

• Yamamura, Tomohiko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Tomohiko Yamamura, MD, PhD

• Iijima, Kazumoto, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan

Kazumoto Iijima, MD, PhD

• Nozu, Kandai, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Kandai Nozu, MD, PhD

Background

In minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), increased serum anti-nephrin antibody titers and co-localization of nephrin and IgG in kidney tissues have been reported, indicating the involvement of anti-nephrin antibodies in nephrotic syndrome (NS). However, comprehensive studies on the association of kidney tissue-specific anti-nephrin antibodies in nephritis, including NS, are lacking.

Methods

To investigate the co-localization of IgG and nephrin, we included 52 kidney tissue samples, comprising NS in the acute phase (n = 25；MCD n=13, FSGS n=7, diffuse mesangial proliferation(DMP) n=5), NS in remission (n = 6), NS with monogenic variants (n = 3), and other kidney diseases (n = 18). The age of patients ranged from 0 to 88 years. We performed double-immunofluorescence staining of nephrin/IgG on unfixed frozen sections and subsequently evaluated the nephrin/IgG co-localization using optical sectioning in a fluorescence microscope.

Results

In acute phase NS, nephrin/IgG co-localization was observed in 80% (20/25) of cases. The proportions of observed nephrin/IgG co-localization were 88% (14 of 16) in pediatric cases (age at onset: 0-16 years) and 67% (6 of 9) in adult cases (age at onset: 47-88 years). Specifically, co-localization was observed in 85% (11 of 13) of MCD cases, 71% (5 of 7) of FSGS cases, and 80% (4 of 5) of DMP cases. Except for 1 case with NS in remission and 1 case with asymptomatic proteinuria (which later developed into NS and responded to steroids), co-localization was not observed in cases with NS in remission, NS with monogenic variants, or other kidney diseases.

Conclusion

In acute phase NS, nephrin/IgG co-localization was observed with high probability, strongly suggesting an association of anti-nephrin antibodies with the onset of idiopathic NS (INS). Staining of kidney tissue is fast, simple, and effective for investigating the pathogenesis of INS and for differential diagnosis of immune-mediated NS from other diseases, including genetic NS.