通过RNA测序转录组分析确定ABO血型不相容肾移植中B细胞受体的VDJ基因使用情况。
VDJ gene usage among B-cell receptors in ABO-incompatible kidney transplantation determined by RNA-seq Transcriptomic analysis.
作者信息
Jeon Hee Jung, Kim Kwangsoo, Lee Jae-Ghi, Jang Joon Young, Choi Seongmin, Fang Taishi, Yan Ji-Jing, Han Miyeun, Jeong Jong Cheol, Lee Kyoung-Bun, Kim Tae Jin, Ahn Curie, Yang Jaeseok
机构信息
Department of Internal Medicine, Hallym University College of Medicine, 150 Seongan-ro, Gangdong-gu, Seoul, 05355, Republic of Korea.
Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
出版信息
BMC Nephrol. 2017 Nov 28;18(1):340. doi: 10.1186/s12882-017-0770-8.
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.
背景
关于肾移植中B细胞亚型及B细胞受体的V(D)J基因使用情况的研究较少。本研究旨在调查与ABO血型相合（ABOc）肾移植（KT）受者相比，ABO血型不相合（ABOi）肾移植受者的V(D)J基因片段使用情况。
方法
我们选取了16例具有免疫适应的ABOi肾移植患者（ABOiA）、6例ABOc稳定肾移植患者（ABOcS）以及6例在第10天经活检证实为急性抗体介导排斥反应的ABOi肾移植患者（ABOiR），这些患者的移植组织样本于2010年至2014年间存储在生物样本库中。通过RNA测序（RNA-seq）对移植组织的完整转录组进行测序和分析。使用国际免疫遗传学信息系统（IMGT®）对V(D)J基因片段使用情况进行深入比较。
结果
28例肾移植受者的平均年龄为43.3±12.8岁，53.6%为男性。按家族分类，IGHV3、IGHJ⁴、IGLV2和IGLJ3基因片段在所有组中使用最为频繁，且在三组患者中其使用情况无统计学差异。虽然IGKV3在ABOiA组和ABOiR组中使用最为频繁，但IGKV1在ABOcS组中最为常用。此外，虽然IGKJ1在ABOiA组和ABOcS组中最为常用，但IGKJ4在ABOiR组中使用最为频繁。根据单个基因片段，IGHV4 - 34和IGHV4 - 30 - 2在ABOiR组中的使用比在ABOiA组中更常见，IGHV6 - 1在ABOcS组中的使用比在ABOiR组中更常见。IGLV7 - 43在ABOcS组中的使用比在ABOi组中更常见。然而，技术变异性、样本量小以及利妥昔单抗或HLA错配的潜在混杂效应是我们研究的局限性。
结论
我们的研究结果表明，RNA测序转录组分析可以提供关于ABOi肾移植中B细胞受体的V(D)J基因使用情况以及免疫适应和免疫反应机制的信息。
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