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PSMP Is Discriminative for Chronic Active Antibody-Mediated Rejection and Associate With Intimal Arteritis in Kidney
Panpan Zhan1,2,3, Haizheng Li4, Mingzhe Han5
1Department of Kidney Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
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.
Insights
PC3-secreted microprotein (PSMP) is crucial in chronic active antibody-mediated rejection (CAAMR) progression, driving macrophage infiltration and intimal arteritis. Targeting PSMP may improve kidney transplant outcomes.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pathology
Background:
- Chronic active antibody-mediated rejection (CAAMR) and chronic antibody-mediated rejection (CAMR) significantly impair long-term kidney allograft survival.
- Early intervention in CAAMR is critical to prevent irreversible damage and progression to CAMR.
Purpose of the Study:
- To investigate the role of PC3-secreted microprotein (PSMP) in the progression of CAAMR and CAMR.
- To identify potential diagnostic biomarkers and therapeutic targets for CAAMR.
Main Methods:
- Analysis of PSMP expression in kidney allograft biopsy samples from CAAMR, CAMR, and control patients.
- Assessment of macrophage infiltration (CD68+ cells) and intimal arteritis (v-lesion score) in relation to PSMP levels.
- Correlation analysis between PSMP expression, macrophage infiltration, and clinical outcomes.
Main Results:
- PSMP expression was significantly elevated in CAAMR biopsies, distinguishing it from CAMR and non-rejection cases.
- Increased CD68+ macrophage infiltration correlated significantly with PSMP expression in CAAMR.
- PSMP levels were associated with intimal arteritis (v-lesion) and graft dysfunction, suggesting a role in allograft loss.
Conclusions:
- PSMP is a key factor in CAAMR progression, promoting macrophage recruitment and intimal arteritis.
- PSMP represents a potential histopathological diagnostic biomarker for CAAMR.
- Targeting PSMP could offer a novel therapeutic strategy for preventing kidney allograft loss in CAAMR.
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