Immune Netw.
2018 Oct;18(5):e36. 10.4110/in.2018.18.e36.
Validation Study of an Operational Tolerance Signature in Korean Kidney Transplant Recipients
- Affiliations
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- 1Division of Nephrology, Department of Internal Medicine, Kyung Hee University, Seoul 02447, Korea. lshkidney@khu.ac.kr
- 2Transplant Research Center, Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. chungbh@catholic.ac.kr
- 3Division of Nephrology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu 41404, Korea.
- 4Department of Surgery, Samsung Medical Center, Seoul 06351, Korea.
- 5Division of Nephrology, Department of Internal Medicine, Inje University College of Medicine, Busan 47392, Korea.
- KMID: 2424202
- DOI: http://doi.org/10.4110/in.2018.18.e36
Abstract
- Operational tolerance (OT), defined as maintaining stable graft function without immunosuppression after transplant surgery, is an ideal goal for kidney transplant recipients (KTRs). Recent investigations have demonstrated the distinctive features of B cells, T cells, and dendritic cell-related gene signatures and the distributions of circulating lymphocytes in these patients; nonetheless, substantial heterogeneities exist across studies. This study was conducted to determine whether previously reported candidate gene biomarkers and the profiles of lymphocyte subsets of OT could be applied in Korean KTRs. Peripheral blood samples were collected from 153 patients, including 7 operationally tolerant patients. Quantitative real-time PCR and flow cytometry were performed to evaluate gene expression and lymphocyte subsets, respectively. Patients with OT showed significantly higher levels of B cell-related gene signatures (IGKV1D-13 and IGKV4-1), while T cell-related genes (TOAG-1) and dendritic cell-related genes (BNC2, KLF6, and CYP1B1) were not differentially expressed across groups. Lymphocyte subset analyses also revealed a higher proportion of immature B cells in this group. In contrast, the distributions of CD4⺠T cells, CD8⺠T cells, mature B cells, and memory B cells showed no differences across diagnostic groups. An OT signature, generated by the integration of IGKV1D-13, IGKV4-1, and immature B cells, effectively discriminated patients with OT from those in other diagnostic groups. Finally, the OT signature was observed among 5.6% of patients who had stable graft function for more than 10 years while on immunosuppression. In conclusion, we validated an association of B cells and their related signature with OT in Korean KTRs.
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