Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation

IntroductionPorcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear.MethodsWe retrospectively analyzed 12 kidney transplant recipients receiving pALG, and additional recipients receiving rabbit anti-human...

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Main Authors: Limin Zhang, Haoyong Zou, Xia Lu, Huibo Shi, Tao Xu, Shiqi Gu, Qinyu Yu, Wenqu Yin, Shi Chen, Zhi Zhang, Nianqiao Gong
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1124790/full
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author Limin Zhang
Haoyong Zou
Xia Lu
Huibo Shi
Tao Xu
Shiqi Gu
Qinyu Yu
Wenqu Yin
Shi Chen
Zhi Zhang
Nianqiao Gong
author_facet Limin Zhang
Haoyong Zou
Xia Lu
Huibo Shi
Tao Xu
Shiqi Gu
Qinyu Yu
Wenqu Yin
Shi Chen
Zhi Zhang
Nianqiao Gong
author_sort Limin Zhang
collection DOAJ
description IntroductionPorcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear.MethodsWe retrospectively analyzed 12 kidney transplant recipients receiving pALG, and additional recipients receiving rabbit anti-human thymocyte immunoglobulin (rATG), basiliximab, or no induction therapy as a comparison group.ResultspALG showed high binding affinity to peripheral blood mononuclear cells (PBMCs) after administration, immediately depleting blood lymphocytes; an effect that was weaker than rATG but stronger than basiliximab. Single-cell sequencing analysis showed that pALG mainly influenced T cells and innate immune cells (mononuclear phagocytes and neutrophils). By analyzing immune cell subsets, we found that pALG moderately depleted CD4+T cells, CD8+T cells, regulatory T cells, and NKT cells and mildly inhibited dendritic cells. Serum inflammatory cytokines (IL-2, IL-6) were only moderately increased compared with rATG, which might be beneficial in terms of reducing the risk of untoward immune activation. During 3 months of follow-up, we found that all recipients and transplanted kidneys survived and showed good organ function recovery; there were no cases of rejection and a low rate of complications.DiscussionIn conclusion, pALG acts mainly by moderately depleting T cells and is thus a good candidate for induction therapy for kidney transplant recipients. The immunological features of pALG should be exploited for the development of individually-optimized induction therapies based on the needs of the transplant and the immune status of the patient, which is appropriate for non-high-risk recipients.
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spelling doaj.art-f1dee61e91fd4e8ab51258f1c9c5deaf2023-03-09T04:31:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11247901124790Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantationLimin Zhang0Haoyong Zou1Xia Lu2Huibo Shi3Tao Xu4Shiqi Gu5Qinyu Yu6Wenqu Yin7Shi Chen8Zhi Zhang9Nianqiao Gong10Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, ChinaDepartment of Research and Development, Wuhan Institute of Biological Products, Wuhan, ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, ChinaDepartment of Intensive Care Unit, Wuhan Fourth Hospital, Wuhan, ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, ChinaDepartment of Research and Development, Wuhan Institute of Biological Products, Wuhan, ChinaDepartment of Research and Development, Wuhan Institute of Biological Products, Wuhan, ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, ChinaDepartment of Research and Development, Wuhan Institute of Biological Products, Wuhan, ChinaInstitute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, ChinaIntroductionPorcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear.MethodsWe retrospectively analyzed 12 kidney transplant recipients receiving pALG, and additional recipients receiving rabbit anti-human thymocyte immunoglobulin (rATG), basiliximab, or no induction therapy as a comparison group.ResultspALG showed high binding affinity to peripheral blood mononuclear cells (PBMCs) after administration, immediately depleting blood lymphocytes; an effect that was weaker than rATG but stronger than basiliximab. Single-cell sequencing analysis showed that pALG mainly influenced T cells and innate immune cells (mononuclear phagocytes and neutrophils). By analyzing immune cell subsets, we found that pALG moderately depleted CD4+T cells, CD8+T cells, regulatory T cells, and NKT cells and mildly inhibited dendritic cells. Serum inflammatory cytokines (IL-2, IL-6) were only moderately increased compared with rATG, which might be beneficial in terms of reducing the risk of untoward immune activation. During 3 months of follow-up, we found that all recipients and transplanted kidneys survived and showed good organ function recovery; there were no cases of rejection and a low rate of complications.DiscussionIn conclusion, pALG acts mainly by moderately depleting T cells and is thus a good candidate for induction therapy for kidney transplant recipients. The immunological features of pALG should be exploited for the development of individually-optimized induction therapies based on the needs of the transplant and the immune status of the patient, which is appropriate for non-high-risk recipients.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1124790/fullporcine anti-human lymphocyte immunoglobulinlymphocyte-depletingkidney transplantationinduction therapylymphocyte
spellingShingle Limin Zhang
Haoyong Zou
Xia Lu
Huibo Shi
Tao Xu
Shiqi Gu
Qinyu Yu
Wenqu Yin
Shi Chen
Zhi Zhang
Nianqiao Gong
Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
Frontiers in Immunology
porcine anti-human lymphocyte immunoglobulin
lymphocyte-depleting
kidney transplantation
induction therapy
lymphocyte
title Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
title_full Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
title_fullStr Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
title_full_unstemmed Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
title_short Porcine anti-human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
title_sort porcine anti human lymphocyte immunoglobulin depletes the lymphocyte population to promote successful kidney transplantation
topic porcine anti-human lymphocyte immunoglobulin
lymphocyte-depleting
kidney transplantation
induction therapy
lymphocyte
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1124790/full
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