Efficacy and Safety of Iguratimod Supplement to the Standard Immunosuppressive Regimen in Highly Mismatched Renal Transplant Recipients: A Pilot Study.

Jun Tao,Min Gu,Li Sun,Zhengkai Huang,Hengcheng Zhang,Ruoyun Tan,Xiaobin Ju,Shuang Fei,Zhijian Han,Hao Chen,Zijie Wang,Haiwei Yang

doi:10.3389/fimmu.2021.738392

Abstract

Iguratimod (IGU) can mitigate the symptoms of rheumatoid arthritis through its anti-inflammatory effects. The objective of this study was to investigate the clinical efficacy and safety of IGU in highly HLA-mismatched renal transplant recipients, in combination with standard immunosuppressive regimen. This pilot study was designed as an open-label, blank-control, randomized clinical trial on patients recruited from a single transplant center in China. Patients who met the inclusion criteria were randomized to the IGU (n=27) and blank control (n=27) groups. IGU was administrated with the conventional triple immunosuppressive protocol for 52 weeks after kidney transplantation. The incidence of biopsy-proven acute rejection rate was 14.8% (4/27) in the IGU group and 29.6% (8/27) in the control group, P = 0.19. The clinical rejection rate was also substantially reduced in the IGU group (3.7% vs. 18.5%, P = 0.08). De novo donor-specific antibody also showed a decline trend in the IGU group after 52 weeks. The graft function and incidence of adverse events were similar between the two groups. In addition, IGU intervention significantly decreased the number of NK cells throughout the follow-up. In conclusion, our study has shown the possibility that IGU could reduce the allograft rejection rate and de novo DSA with appreciable safety in combination with conventional immunosuppressants. Formal clinical trials were warranted based on current findings.

Highlights

Kidney transplantation is the optimal treatment for end-stage renal failure and improves survival and quality of life in most cases [1]
We found that IGU mitigated antibody-mediated rejection (ABMR) in a presensitized mouse transplant model, which is not surprising given the similarities between autoimmune diseases and graft rejection
Three patients (1 in the IGU and 2 in the control group) withdrew voluntarily, one patient in the IGU group was excluded due to residential relocation, one patient in the control group withdrew on account of a severe surgical complication, and one patient in the control group died from pulmonary infection

Summary

Introduction

Kidney transplantation is the optimal treatment for end-stage renal failure and improves survival and quality of life in most cases [1]. T cell-targeting immunosuppressive drugs have significantly reduced the occurrence of T cell-mediated rejection (TCMR) and prolonged graft survival among the recipients, they increase the risk of opportunistic infections and tumorigenesis. The role of humoral immunity in organ transplantation and graft rejection is less known. De novo donorspecific antibody (DSA) and non-human lymphocyte antigen (HLA) antibodies are primary mediators of antibody-mediated rejection (ABMR) and early graft dysfunction [2]. Preformed DSA increases the immunological risk in potential recipients, whereas a high degree of HLA mismatch is another independent risk factor for poor graft survival [3]. A prophylactic anti-humoral immunity strategy is urgently needed for the recipients with high immunologic risks

Objectives

Methods

Results

Conclusion