PSMP Is Discriminative for Chronic Active Antibody-Mediated Rejection and Associate With Intimal Arteritis in Kidney Transplantation.

Panpan Zhan,Yingxin Fu,Zhen Wang,Mingzhe Han,Jinpeng Tu,Haizheng Li,Jie Zhao,Xiaofeng Shi

doi:10.3389/fimmu.2021.661911

Abstract

Chronic active antibody-mediated rejection (CAAMR) is an intermediate process that occurs during the development of chronic antibody-mediated rejection (CAMR), which is a key problem associated with the long-term kidney grafts survival. This study investigated the role played by PC3-secreted microprotein (PSMP) in the progression of CAAMR and CAMR. We showed that CAAMR and CAMR patients’ allografts dysfunction with declined survival rate, which suggested that earlier diagnosis and treatment of CAAMR might be important to prevent irreversible chronic injury of CAMR progression. We found PSMP was an important factor in the development of chronic antibody-mediated rejection. The PSMP expression increased significantly in CAAMR biopsy samples but not in CAMR and control patients, which distinguished CAAMR patients from CAMR and non-rejection patients. Moreover, our results showed that infiltration of CD68+ macrophages in CAAMR increased, and the correlation between CD68+ macrophages and PSMP expression in CAAMR patients was significant. Additionally, our data also revealed that intimal arteritis (v-lesion) accompanied by increased macrophage infiltration might have contributed to more graft loss in CAAMR, and PSMP expression was significantly associated with the v-lesion score. These results indicated that PSMP played an important role in the recruitment of macrophages and promote intimal arteritis inducing allograft lost in CAAMR progression. In future study PSMP could be a potential histopathological diagnostic biomarker and treatment target for CAAMR in kidney transplantation.

Highlights

Chronic active antibody-mediated rejection (CAAMR) is an intermediate process that occurs during the development of chronic antibody-mediated rejection (CAMR), which has been recognized recently
The CAAMR and CAMR groups presented positive anti‐human leukocyte antigen (HLA) donor-specific antibodies (DSA) at the time of biopsy compared to Control group (p < 0.05), and 14 of 17 CAAMR patients were positive for anti‐HLA class II antibody, as were 4 of 7 in CAMR patients
PC3-secreted microprotein (PSMP) expression in graft biopsy tissues may be more meaningful for the diagnosis of CAAMR and distinguishing from CAMR

Summary

Introduction

Chronic active antibody-mediated rejection (CAAMR) is an intermediate process that occurs during the development of chronic antibody-mediated rejection (CAMR), which has been recognized recently. CAAMR leads to the gradual loss of allograft, becoming an obstacle to the long-term survival of renal allografts [1]. Significant improvements in short-term renal graft survival have been achieved in recent decades due to the continuous updating of immunosuppressive agents, such as calcineurin inhibitors, which greatly reduce the occurrence of T cell-mediated rejection (TCMR) [2]. Long-term renal allograft loss caused by CAAMR has no significant improvements without effective therapeutic drugs [3, 4]. It’s lacking specific molecular pathological biomarkers available for expressing the intermediate injury from CAAMR progress to CAMR [7]

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Results

Conclusion