Validation Study of an Operational Tolerance Signature in Korean Kidney Transplant Recipients.
- Author:
Yu Ho LEE
1
;
Jung Woo SEO
;
Yang Gyun KIM
;
Ju Young MOON
;
Jin Sug KIM
;
Kyung Hwan JEONG
;
Bo mi KIM
;
Kyoung Woon KIM
;
Chul Woo YANG
;
Chan Duck KIM
;
Jae Berm PARK
;
Yeong Hoon KIM
;
Byung Ha CHUNG
;
Sang Ho LEE
Author Information
- Publication Type:Original Article
- Keywords: Operational tolerance; Kidney transplantation; Biomarkers; mRNA; B-lymphocytes
- MeSH: B-Lymphocytes; Biomarkers; Flow Cytometry; Gene Expression; Humans; Immunosuppression; Kidney Transplantation; Kidney*; Lymphocyte Subsets; Lymphocytes; Memory; Precursor Cells, B-Lymphoid; Real-Time Polymerase Chain Reaction; RNA, Messenger; T-Lymphocytes; Transplant Recipients*; Transplants
- From:Immune Network 2018;18(5):e36-
- CountryRepublic of Korea
- Language:English
- 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⁺ T cells, CD8⁺ 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.
