Immunomonitoring of renal transplant recipients in the early posttransplant period by sequential analysis of chemokine and chemokine receptor gene expression in peripheral blood mononuclear cells.

摘要

INTRODUCTION: We sought to determine whether sequential changes in chemokine ligand/receptor gene expression in the early posttransplant period of human renal allografts can be detected in peripheral blood mononuclear cells (PBMCs) and whether any such changes are predictive of clinical events. METHODS: Blood samples from 106 renal transplant recipients and 29 donor nephrectomy patients were taken preoperatively and daily for 14 days. Within the study period 22 patients had biopsy-proven acute rejection. From each blood sample PBMCs were separated and gene expression levels for chemokines CCL3, CCL4, CCL5, CXCL10, and their receptors CCR1, CCR5, and CXCR3, were determined using real-time quantitative PCR. RESULTS: Different gene expression patterns were seen between the rejector and nonrejector groups with decreases in CCL4 and CCR5 expression on days 6 to 8 and increases in CCR1 expression on days 9 and 10 posttransplant. With CXCL10, decreases in expression were seen in the nonrejector group but increases were seen in the rejector group posttransplant. With data aligned to time of rejection diagnosis, statistically significant increases, that preceded the clinical detection of acute rejection were seen in CCR1 and CXCL10 expression. Both their expression levels returned to pretransplant baseline values after successful antirejection therapy. CONCLUSION: We have demonstrated that changes in chemokine receptor/ligand gene expression by sequential monitoring in PBMCs can be detected in the early posttransplant period. In particular, CCR1 and CXCL10, which showed increased expression prior to rejection and returned to baseline levels with antirejection therapy, may have potential use in immunomonitoring and as predictive factors of rejection prior to its clinical manifestation.