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

Front Immunol. 2023 Mar 9:14:1124790. doi: 10.3389/fimmu.2023.1124790. eCollection 2023.

Abstract

Introduction: Porcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear.

Methods: We 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.

Results: pALG 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.

Discussion: In 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.

Keywords: induction therapy; kidney transplantation; lymphocyte; lymphocyte-depleting; porcine anti-human lymphocyte immunoglobulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basiliximab
  • Immunosuppressive Agents*
  • Kidney Transplantation*
  • Leukocytes, Mononuclear
  • Lymphocytes
  • Rabbits
  • Retrospective Studies
  • Swine

Substances

  • Immunosuppressive Agents
  • Basiliximab

Grants and funding

This work was supported by grants to NG from the National Natural Science Foundation of China (No. 81873623 and 82170772), to NG from the Clinical Research Physician Program of Tongji Medical College, HUST, to NG from the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province (CXPJJH122001-2210), and to J Yu from the Tongji Scientific Project (2022044), to ZS Chen from the grants from the Health Commission of Hubei Province (WJ2021C001) and Key Research and Development Plan of Hubei Province (2022BCA015).