A Diagnostic Biomarker Model Associated with Immune Infiltration in Patients with Antibody-Mediated Rejection after Kidney Transplantation

Background: In spite of advances in development and application of immunosuppressive agents, the long-term survival of grafts still needs to be advanced caused by antibody-mediated rejection (ABMR). Many researchers have paid attention to this area. However, little was known about the role of genes and immune cells in the development of ABMR. Methods: In total, 2533 biopsy cases from four different cohorts were collected. Three Gene Expression Omnibus (GEO) datasets (GSE36059, GSE98320 and GSE12403) were used as the training set, and one GEO dataset and twenty biopsy samples from our center were used for validation. The potential diagnostic prediction value of the signature and immune profiles were also explored. Findings: The LASSO regression model and PPI network were performed to search candidate biomarkers. LAPTM5, GBP2, CCL5 and KLRD1 were obtained as diagnostic biomarkers (AUC = 0·934, 95% CI 0·923-0·943). Immune cell infiltration analysis revealed that γδ T cells which could secrete IL-17A were most related with four biomarkers. The infiltration of γδ T cells and IL-17A were significantly higher in ABMR group than that in ST group. Interpretation: We have identified and established a diagnostic model containing four transcripts as diagnostic biomarkers of ABMR following kidney transplantation. Several types of immune cells were inferred to be involved in the process of ABMR. Among these, γδ T cells were most related with four biomarkers, which may promote ABMR by producing IL-17A. Funding: This work was supported by the National Natural Science Foundation of China [grant numbers 82070769, 81900684, 81870512, 81770751, 81570676, 81470981, 81100532], Project of Jiangsu Province for Important Medical Talent [grant number ZDRCA2016025], the “333 High Level Talents Project” in Jiangsu Province [grant numbers BRA2017532, BRA2016514, BRA2015469], the Standardized Diagnosis and Treatment Research Program of Key Diseases in Jiangsu Province [grant number BE2016791], the Open Project Program of Health Department of Jiangsu Province [grant number JSY-2-2016-099], Jiangsu Province Natural Science Foundation Program [grant number BK20191063]. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the local ethics committee of the First Affiliated Hospital of Nanjing Medical University (2016-SR-029).