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Abstract: SA-PO0727

Comparative Proteomic Analysis of Tonsils in IgAN

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Tsuji, Yudai, Department of Biomedical Molecular Sciences, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
  • Ohyama, Yukako, Department of Biomedical Molecular Sciences, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
  • Tsuboi, Naotake, Department of Nephrology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
  • Takahashi, Kazuo, Department of Biomedical Molecular Sciences, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
Background

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, with 30-40% of cases progressing to end-stage renal disease. Tonsillectomy combined with steroid pulse therapy is used to manage the IgAN-specific drivers for nephron loss in Japan. Tonsillectomy has been reported to have a favorable effect on preventing end-stage renal disease in patients with IgAN, suggesting that tonsils play an important role in the pathogenesis of IgA nephropathy. In this study, a proteomic analysis of tonsils was performed to detect proteins associated with IgAN pathogenesis.

Methods

Pathology on renal biopsy of patients with IgAN who underwent tonsillectomy showed endocapillary hypercellularity and/or crescent lesions in the Oxford classification . The proteins of germinal center (GC), follicular mantle (FM), T-cell area (TA), and crypt epithelium (CE) were extracted from frozen tonsil tissues from patients with IgAN (n=23) and controls (chronic tonsillitis, n=13) using laser microdissection. Tonsillar proteins were analyzed by label-free quantification using high-resolution mass spectrometry (Orbitrap Fusion; Thermo Fisher Scientific). Protein–protein interaction network analysis was performed using the STRING database (https://string-db.org/).

Results

Tonsillar proteomic analysis quantified 2854, 2844, 2805 and 2782 proteins in GC, FM, TA and CE, respectively. Of those, 195 proteins in GC, 252 proteins in FM, 174 proteins in TA, and 258 proteins in CE had significantly different abundances in patients with IgAN than in the controls (FC ≥ ± 1.5, P < 0.05). The protein–protein interaction networks of significantly altered proteins revealed changes in the immune response-regulating signaling pathway within CE, the immunological synapse within GC, the innate immune response and the defense response to viruses within FM and the inflammatory response and the regulation of cytokine production within TA.

Conclusion

Proteomic profiling revealed changes in the immune response in the tonsils of patients with IgAN compared with those with tonsillitis. These tonsillar proteomic results provide valuable insights for identifying potential protein targets to control IgAN.

Digital Object Identifier (DOI)