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ABO血型不相容肾移植患者外周血中B细胞受体的VDJ基因使用情况

VDJ Gene Usage of B Cell Receptors in Peripheral Blood of ABO-incompatible Kidney Transplantation Patients.

作者信息

Jeon H J, Fang T, Lee J-G, Jang J Y, Kim K, Choi S, Yan J-J, Ryu J H, Koo T Y, Ahn C, Yang J

机构信息

Department of Internal Medicine, Hallym University College of Medicine, Seoul, Republic of Korea.

Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

Transplant Proc. 2018 May;50(4):1056-1062. doi: 10.1016/j.transproceed.2018.01.047.

Abstract

INTRODUCTION

B cell subtypes and immunoglobulin variable (V), diversity (D), joining (J) gene segment usage of B cell receptors in ABO-incompatible (ABOi) kidney transplantation (KT) in comparison to ABO-compatible KT have not been studied. The aims of this study were to analyze the VDJ gene segment usages of B cell receptors in peripheral blood of ABOi KT recipients.

METHODS

Eighteen ABOi KT patients with accommodation (ABOiA), 10 ABO-compatible stable KT patients (ABOcS), and 10 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10 after transplantation were selected. Complete transcriptomes of their peripheral blood samples were sequenced and analyzed through RNA sequencing.

RESULTS

By family, immunoglobulin heavy chain variable 3 (IGHV3), immunoglobulin light kappa chain variable 1 (IGKV1), immunoglobulin light lambda chain variable 2 (IGLV2), and immunoglobulin light lambda chain joining 3 (IGLJ3) gene segments were most frequently used in all groups, and their usage was not statistically different among the three groups except for IGHV3 and IGKV1. IGKV1 was more frequently used in the ABOiA group than in the ABOcS group. According to individual gene segments, IGHV3-7, IGHV3-15, IGHV4-59, IGKV3-11, IGLV1-44, IGLV2-14, IGLV4-69, and IGLV7-46 were more frequently used in the ABOcS group than other groups, and IGKV3-7 was more frequently used in the ABOiR group than other groups. IGLV5-52 and IGLV7-43 were more frequently used in the ABOiA group than in ABOcS group.

CONCLUSIONS

Our findings suggest that RNA sequencing transcriptomic analyses of peripheral blood can provide information on the VDJ gene usage of B cell receptors and the mechanisms of accommodation and immune reaction in ABOi KT.

摘要

引言

与ABO血型相合的肾移植(KT)相比,ABO血型不相合(ABOi)肾移植中B细胞亚型及B细胞受体的免疫球蛋白可变(V)、多样性(D)、连接(J)基因片段的使用情况尚未得到研究。本研究的目的是分析ABOi肾移植受者外周血中B细胞受体的VDJ基因片段使用情况。

方法

选取18例具有免疫适应的ABOi肾移植患者(ABOiA)、10例ABO血型相合的稳定肾移植患者(ABOcS)以及10例移植后第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)。对其外周血样本的完整转录组进行测序,并通过RNA测序进行分析。

结果

按家族分类,免疫球蛋白重链可变区3(IGHV3)、免疫球蛋白轻链κ可变区1(IGKV1)、免疫球蛋白轻链λ可变区2(IGLV2)和免疫球蛋白轻链λ连接区3(IGLJ3)基因片段在所有组中使用最为频繁,除IGHV3和IGKV1外,这三个组之间的使用情况无统计学差异。IGKV1在ABOiA组中的使用频率高于ABOcS组。根据单个基因片段,IGHV3-7、IGHV3-15、IGHV4-59、IGKV3-11、IGLV1-44、IGLV2-14、IGLV4-69和IGLV7-46在ABOcS组中的使用频率高于其他组,而IGKV3-7在ABOiR组中的使用频率高于其他组。IGLV5-52和IGLV7-43在ABOiA组中的使用频率高于ABOcS组。

结论

我们的研究结果表明,对外周血进行RNA测序转录组分析可以提供有关ABOi肾移植中B细胞受体的VDJ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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