Abstract: FR-PO721
An Increase in TCR/BCR Repertoire Clonality by Prednisolone Therapy and Recovery of the Diversity by Rituximab in Childhood Idiopathic Nephrotic Syndrome
Session Information
- Pediatric Nephrology - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Horinouchi, Tomoko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Kimura, Yuka, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Inoki, Yuta, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Ichikawa, Yuta, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Tanaka, Yu, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Kitakado, Hideaki, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Ueda, Chika, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Sakakibara, Nana, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Nagano, China, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Yamamura, Tomohiko, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Fujimura, Junya, Department of Pediatrics, Kakogawa Central City Hospital, Kakogawa, Hyogo, Japan
- Kamiyoshi, Naohiro, Department of Pediatrics, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan
- Ishimori, Shingo, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Kaito, Hiroshi, Department of Nephrology, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Hyogo, Japan
- Shima, Yuko, Department of Pediatrics, Wakayama Medical University, Wakaya, Wakayama, Japan
- Nakamura, Yukio, Repertoire Genesis Inc., Ibaraki, Japan
- Sakai, Asako, Zenyaku Kogyo Co., Ltd., Tokyo, Tokyo, Japan
- Okugaito, Izumi, Zenyaku Kogyo Co., Ltd., Tokyo, Tokyo, Japan
- Nozu, Kandai, Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
- Iijima, Kazumoto, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Hyogo, Japan
Background
In diseases related to autoimmunity, it is known that the T-cell receptors (TCR) / B-cell receptors (BCR) repertoire along with lymphocyte subpopulations exhibits various characteristics, but there is no data available for idiopathic nephrotic syndrome (NS) in children.
Methods
We conducted TCR / BCR repertoire analysis on peripheral blood mononuclear cells using high-throughput sequence method on 45 pediatric nephrotic syndrome patients and 11 non-nephrotic individuals with abnormal urinalysis as controls, totaling 96 samples (control n=11; initial-onset NS n=70; complicated NS with rituximab (Rtx) treatment n=15).
Results
There was no significant difference in the diversity of TCR/BCR repertoires between the control group (n=11) and the initial-onset pretreatment NS group (n=36). When comparing pairs before and after prednisolone (PSL) therapy (n=34), the diversity of TCR/BCR repertoire was decreased; Shannon index (e.g. TRA 6.99 (SD 0.99) vs 6.05 (SD 1.17) p<0.0001, IgM 7.79 (SD 0.85) vs 7.52 (SD 0.91) p<0.03).
In patients with pre-Rtx treatment complicated NS (n=9), the diversity of TCR/BCR repertoire was decreased significantly compared to patients with initial-onset NS; Shannon index (e.g. TRA 6.97 (SD 0.97) vs 5.32 (SD 1.15) p<0.0003, IgM 7.78 (SD 0.86) vs 6.69 (SD 0.83) p<0.003). After Rtx treatment, when B cells recovered, recovery of the diversity was also observed (n=6).
Conclusion
While no changes were observed in initial-onset NS, PSL treatment led to an increase in specific clones. A decrease of diversity in TCR/BCR repertoires was seen in complicated NS requiring Rtx, while diversity recovered after rituximab administration, likely promoting restoration of immune tolerance.
Funding
- Commercial Support – Zenyaku kogyo