Abstract
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).
Highlights
Studies on B-cell subtypes and V(D)J gene usage of B-cell receptors in kidney transplants are scarce
In terms of individual heavy chain V gene segments, IGHV4–34 and IGHV4– 30-2 were more often used in the antibody-mediated rejection (ABOiR) group than in the ABOi kidney transplant (KT) patients with accommodation (ABOiA) group, and IGHV6–1 was more often used in the ABOc stable KT patients (ABOcS) group than in the ABOiR group
While the immunoglobulin light kappa chain V domain 3 (IGKV3) gene segment family was most frequently used in both the ABOiA and ABOiR groups, the IGKV1 gene segment was most commonly used in the ABOcS group
Summary
Studies on B-cell subtypes and V(D)J gene usage of B-cell receptors in kidney transplants are scarce. ABO-incompatible (ABOi) KT is one solution to this problem and is known to increase organ transplantation by approximately 20% Development of both more potent immunosuppressive agents and desensitization methods has increased the number of ABOi KT and has improved its outcomes [2]. Pre-transplantation desensitization with anti-CD20 monoclonal antibody and plasmapheresis is performed to suppress the production of antiABO antibody and to remove pre-formed antibody. These desensitization therapies may prevent the occurrence of hyperacute and acute antibody-mediated rejection (AMR) [3]. There is a lack of studies on what kinds of B-cell subtypes play key roles in these immune responses, and studies regarding the variable (V), diversity (D), and joining (J) gene segment usages of B-cell receptors in ABOi KT are scarce
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