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High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report

Background: Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is essential to monitor patients’ immune status for detecting a rejection/graft failure earl...

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Autores principales: Wu, Tsai-Hung, Liao, Hsien-Tzung, Li, Tzu-Hao, Tsai, Hung-Cheng, Lin, Niang-Cheng, Chen, Cheng-Yen, Tsai, Shih-Feng, Huang, Tzu-Hao, Tsai, Chang-Youh, Yu, Chia-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181060/
https://www.ncbi.nlm.nih.gov/pubmed/35683373
http://dx.doi.org/10.3390/jcm11112980
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author Wu, Tsai-Hung
Liao, Hsien-Tzung
Li, Tzu-Hao
Tsai, Hung-Cheng
Lin, Niang-Cheng
Chen, Cheng-Yen
Tsai, Shih-Feng
Huang, Tzu-Hao
Tsai, Chang-Youh
Yu, Chia-Li
author_facet Wu, Tsai-Hung
Liao, Hsien-Tzung
Li, Tzu-Hao
Tsai, Hung-Cheng
Lin, Niang-Cheng
Chen, Cheng-Yen
Tsai, Shih-Feng
Huang, Tzu-Hao
Tsai, Chang-Youh
Yu, Chia-Li
author_sort Wu, Tsai-Hung
collection PubMed
description Background: Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is essential to monitor patients’ immune status for detecting a rejection/graft failure early on. Methods: We monitored the sequence change of complementary determining region 3 (CDR3) in B-cell receptor (BCR) immunoglobulin heavy-chain (IGH) immune repertoire (iR) in 14 renal transplant patients using next-generation sequencing (NGS), correlating its diversity to various clinical events occurring after transplantation. BCR-IGH-CDR3 in peripheral blood mononuclear cells was sequenced along the post-transplantation course by NGS using the iRweb server. Results: Datasets covering VDJ regions of BCR-IGH-CDR3 indicated clonal diversity (D50) variations along the post-transplant course. Furthermore, principal component analysis showed the clustering of these sequence variations. A total of 544 shared sequences were identified before transplantation. D50 remained low in three patients receiving rituximab. Among them, one’s D50 resumed after 3 m, indicating graft tolerance. The D50 rapidly increased after grafting and decreased thereafter in four patients without rejection, decreased in two patients with T-cell-mediated rejection (TCMR) and exhibited a sharp down-sliding after 3 m in two patients receiving donations after cardiac death (DCD). In another two patients with TCMR, D50 was low just before individual episodes, but either became persistently low or returned to a plateau, depending on the failure or success of the immunosuppressive treatments. Shared CDR3 clonal expansions correlated to D50 changes. Agglomerative hierarchical clustering showed a commonly shared CDR3 sequence and at least two different clusters in five patients. Conclusions: Clonal diversity in BCR-IGH-CDR3 varied depending on clinical courses of 14 renal transplant patients, including B-cell suppression therapy, TCMR, DCD, and graft tolerance. Adverse events on renal graft failure might lead to different clustering of BCR iR. However, these preliminary data need further verification in further studies for the possible applications of iR changes as genetic expression biomarkers or laboratory parameters to detect renal graft failure/rejection earlier.
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spelling pubmed-91810602022-06-10 High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report Wu, Tsai-Hung Liao, Hsien-Tzung Li, Tzu-Hao Tsai, Hung-Cheng Lin, Niang-Cheng Chen, Cheng-Yen Tsai, Shih-Feng Huang, Tzu-Hao Tsai, Chang-Youh Yu, Chia-Li J Clin Med Article Background: Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is essential to monitor patients’ immune status for detecting a rejection/graft failure early on. Methods: We monitored the sequence change of complementary determining region 3 (CDR3) in B-cell receptor (BCR) immunoglobulin heavy-chain (IGH) immune repertoire (iR) in 14 renal transplant patients using next-generation sequencing (NGS), correlating its diversity to various clinical events occurring after transplantation. BCR-IGH-CDR3 in peripheral blood mononuclear cells was sequenced along the post-transplantation course by NGS using the iRweb server. Results: Datasets covering VDJ regions of BCR-IGH-CDR3 indicated clonal diversity (D50) variations along the post-transplant course. Furthermore, principal component analysis showed the clustering of these sequence variations. A total of 544 shared sequences were identified before transplantation. D50 remained low in three patients receiving rituximab. Among them, one’s D50 resumed after 3 m, indicating graft tolerance. The D50 rapidly increased after grafting and decreased thereafter in four patients without rejection, decreased in two patients with T-cell-mediated rejection (TCMR) and exhibited a sharp down-sliding after 3 m in two patients receiving donations after cardiac death (DCD). In another two patients with TCMR, D50 was low just before individual episodes, but either became persistently low or returned to a plateau, depending on the failure or success of the immunosuppressive treatments. Shared CDR3 clonal expansions correlated to D50 changes. Agglomerative hierarchical clustering showed a commonly shared CDR3 sequence and at least two different clusters in five patients. Conclusions: Clonal diversity in BCR-IGH-CDR3 varied depending on clinical courses of 14 renal transplant patients, including B-cell suppression therapy, TCMR, DCD, and graft tolerance. Adverse events on renal graft failure might lead to different clustering of BCR iR. However, these preliminary data need further verification in further studies for the possible applications of iR changes as genetic expression biomarkers or laboratory parameters to detect renal graft failure/rejection earlier. MDPI 2022-05-25 /pmc/articles/PMC9181060/ /pubmed/35683373 http://dx.doi.org/10.3390/jcm11112980 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Tsai-Hung
Liao, Hsien-Tzung
Li, Tzu-Hao
Tsai, Hung-Cheng
Lin, Niang-Cheng
Chen, Cheng-Yen
Tsai, Shih-Feng
Huang, Tzu-Hao
Tsai, Chang-Youh
Yu, Chia-Li
High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report
title High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report
title_full High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report
title_fullStr High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report
title_full_unstemmed High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report
title_short High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report
title_sort high-throughput sequencing of complementarity determining region 3 in the heavy chain of b-cell receptor in renal transplant recipients: a preliminary report
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181060/
https://www.ncbi.nlm.nih.gov/pubmed/35683373
http://dx.doi.org/10.3390/jcm11112980
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