VDJ Gene Usage among B-Cell Receptors in ABO-incompatible Kidney Transplantation Determined by RNA-seq Transcriptomic Analysis
Hee Jung Jeon1, Kwangsoo Kim2, Jae-Ghi Lee3, Joon Young Jang3, Seongmin Choi2, Taishi Fang3, Ji-Jing Yan3, Miyeun Han4, Jong Cheol Jeong5, Kyoung-Bun Lee6, Tae Jin Kim7, Curie Ahn3,4,8, Jaeseok Yang3,8,9.
1Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea; 2Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea; 3Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea; 4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; 5Department of Nephrology, Ajou University School of Medicine, Suwon, Korea; 6Department of Pathology, Seoul National University Hospital, Seoul, Korea; 7Division of Immunobiology, Sungkyunkwan University School of Medicine, Suwon, Korea; 8Transplantation Center, Seoul National University Hospital, Seoul, Korea; 9Department of Surgery, Seoul National University Hospital, Seoul, Korea
Background: Studies on B-cell subtypes and V(D)J gene usage of B-cell receptors in kidney transplants are scarce. This study aimed to investigate V(D)J gene segment usage in ABO-incompatible (ABOi) kidney transplant (KT) patients compared to that in ABO-compatible (ABOc) KT patients.
Methods: We selected 16 ABOi KT patients with accommodation (ABOiA), 6 ABOc stable KT patients (ABOcS), and 6 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10, whose graft tissue samples had been stored in the biorepository between 2010 and 2014. Complete transcriptomes of graft tissues were sequenced and analyzed through RNA sequencing (RNA-seq). The international ImMunoGeneTics information system (IMGT®) was used for in-depth comparison of V(D)J gene segment usage.
Results: The mean age of the 28 KT recipients was 43.3 ± 12.8 years, and 53.6% were male. By family, IGHV3, IGHJ4, IGLV2, and IGLJ3 gene segments were most frequently used in all groups, and their usage was not statistically different among the three patient groups. While IGKV3 was most frequently used in both the ABOiA and ABOiR groups, IGKV1 was most commonly used in the ABOcS group. In addition, while IGKJ1 was most commonly used in the ABOiA and ABOcS groups, IGKJ4 was most frequently used in the ABOiR group. According to individual gene segments, IGHV4-34 and IGHV4-30-2 were more commonly used in the ABOiR group than in the ABOiA group, and IGHV6-1 was more commonly used in the ABOcS group than in the ABOiR group. IGLV7-43 was more commonly used in the ABOcS group than in the ABOi group. However, technical variability, small sample size, and potential confounding effects of Rituximab or HLA mismatching are limitations of our study.
|Conclusions: Our findings suggest that RNA-seq transcriptomic analyses can provide information on the V(D)J gene usage of B-cell receptors and the mechanisms of accommodation and immune reaction in ABOi KT.
Astellas Pharma Korea, Inc.. The Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (grant NRF-2015M3A9D3051413).
