Validation Study of an Operational Tolerance Signature in Korean Kidney Transplant Recipients

• Published in: Immune network Vol. 18; no. 5; pp. e36 - 13
• Main Authors: Lee, Yu Ho, Seo, Jung-Woo, Kim, Yang Gyun, Moon, Ju-Young, Kim, Jin Sug, Jeong, Kyung-Hwan, Kim, Bo-mi, Kim, Kyoung Woon, Yang, Chul Woo, Kim, Chan-Duck, Park, Jae Berm, Kim, Yeong Hoon, Chung, Byung Ha, Lee, Sang-Ho
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Association of Immunologists 01.10.2018; 대한면역학회
• Subjects: Original; 면역학; Biomarkers; B-lymphocytes; mRNA; Operational tolerance; Kidney transplantation
• ISSN: 1598-2629; 2092-6685
• DOI: 10.4110/in.2018.18.e36

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 ( and ), while T cell-related genes ( ) and dendritic cell-related genes ( , , and ) 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 , 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.