Chemokine and chemokine receptor gene expression in human PBMCs in the early renal post-transplant period

Abstract

The aim of this work was to determine whether sequential changes in chemokine and/or chemokine receptor gene expression in the early post-transplant period of human renal allografts can be detected in PBMCs, and whether any such changes are predictive of clinical events.

Blood samples from 106 renal transplant recipients and 29 donor nephrectomy patients were taken pre-operatively and then daily for 14 days.  Within the two week study period 22 patients had biopsy proven acute rejection.  From each blood sample the PBMCs were separated, their RNA extracted and a fixed quantity reverse transcribed to cDNA.  Using real-time quantitative PCR (5’ nuclease assay by TaqMan® methodology), the gene expression levels for the chemokines CCL3, CCL4, CCL5, CXCL10 and their receptors CCR1, CCR5 and CXCR3 were measured.  The possible endogenous control genes tested were GAPDH, MLN51, YWHAZ, EF-1α and UbcH5B.

Changes in chemokine and chemokine receptor gene expression by sequential monitoring in PBMCs were detected in the early post-transplant period.  Furthermore, different expression patterns between rejector and non-rejector groups for some genes were demonstrated and some of these changes correlated with clinical events. In particular, CCR1 and CXCL10 showed increased expression prior to rejection and returned back to baseline levels with anti-rejection therapy.  The search for a suitable endogenous control gene for use in the gene expression model used in this work was unsuccessfully, with significant changes in expression of all five genes tested at some time point post-transplantation.

This work has demonstrated that changes in chemokine and chemokine receptor gene expression can be detected in PBMCs in the early post-transplant period, and in particular CXCL10 and CCR1 showed changes that correlate with rejection, and therefore may have potential use in immunomonitoring and as predictive factors of rejection prior to its clinical manifestation.

More information

Identifiers

Catalogue record

Export record

ASCII CitationAtomBibTeXData Cite XMLDublin CoreDublin CoreEP3 XMLEndNoteHTML CitationHTML CitationHTML ListJSONMETSMODSMPEG-21 DIDLOpenURL ContextObjectOpenURL ContextObject in SpanRDF+N-TriplesRDF+N3RDF+XMLRIOXX2 XMLReferReference ManagerSimple Metadata