Identifying transcriptional change in renal allografts infected with Cytomegalovirus (CMV) may be important in understanding CMV effects on graft rejection and injury.
We examined transcriptional profiles using Affymetrix WT exon microarrays of 159 biopsies from renal allografts with differing CMV serostatus at 3 months post-transplant. All were from the GOCAR cohort of living and cadaveric transplant recipients from 5 major centres. Differential gene expression (DE) was analyzed using LIMMA methods according to allograft donor (D) recipient (R) CMV serostatus: D-/R-, n=20 ; D+/R+, n=78 ; D-/R+, n=42; D+/R-, n=19. Biologic pathways and potential networks of DE genes were assessed with IPA (www.ingenuity.com).
Differential gene expression (Table 1) shows genes of cell adhesion and ECM organisational processes were the strongest of 273 upregulated biologic processes in the CMV exposed cohort (D+/R-,D+/R+ and D-/R+ versus D-/R-). Signalling pathways identified in the CMV exposed group included hepatic fibrosis activation pathways, and MAPK and endothelin signalling. Nineteen regulatory networks were associated with CMV exposure, with the highest networks being i) cardiovascular system development and function, cell-to-cell signalling/interaction, and tissue development, which have central roles for the upregulated genes FN1 and MMP2; and ii) haematological, immunological and infectious diseases group genes, including upregulated CCL5. Subset analysis of the differing exposed groups versus D-/R- showed fewer genes with > 1.5 fold differences, and no significant biologic processes unqiuely upregulated.
This study demonstrates significant DE within kidney allografts according to CMV serostatus with implications for potential pathways involved in graft injury and repair in CMV exposed transplant recipients.
|Differential gene expression||Biologic processes (p<0.05 and FD>1.5)|
|Total no. p<0.05||Top genes (FD >1.5,p<0.05)||p<0.05|
|D+/R-,D+/R+, D-/R+ versus D-/R-||510||SFRP2, MFAP5, FABP4, CD36* ,CCDC80** ,SAA1 IGJ NEXN, FBN1, ABCC9, COL14A1**, SFRP4, TSHZ2, LUM, CD163, MOXD1,CTSK,COL12A1*, FLJ26056, FN1*, OGN, SPARCL1, LHFP, ADH1B, BANF1||Cell adhesion* Extracellular matrix organisation**|
To cite this abstract in AMA style:Page ALe, Zhang W, Murphy B, Nankivell B, Chapman J, O'Connell P, Alexander S, Rawlinson W. CMV Serostatus Correlation with Early Kidney Allograft Transcriptome Change in the GOCAR Cohort [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/cmv-serostatus-correlation-with-early-kidney-allograft-transcriptome-change-in-the-gocar-cohort/. Accessed July 24, 2021.
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