Gene expression using microarrays in transplant recipients at risk of EBV lymphoproliferation after organ transplantation: preliminary proof-of-concept.
We hypothesized that aspects of the virus-host interaction could be measured to help predict progression to EBV-PTLD. We examined the spectrum of host genes differentially expressed and any relevant clustering in children at risk of EBV lymphoproliferation after organ transplantation. We compared the genes expressed among patients with different levels of viral loads. Gene expression was measured by microarray analysis of RNA from CD19+ B lymphocytes using the Human Genome U133 Plus 2.0 GeneChip. Among 27 samples from 26 transplant recipients, the viral load categories were: low or undetectable loads (LU), n = 14; high or intermediate loads (HI), n = 13. There were seven healthy EBV-seropositive (P) and -seronegative controls (N). Median time of post-transplantation was 0.5 yr (range 0.1-3.8). We identified 24-54 differentially expressed genes in each of four comparisons of HI vs. P, LU vs. P, HI vs. LU, and P vs. N. We identified patterns of 563 gene expressions, creating five clusters aligned with levels of viral load. PTLD occurred in four of five clusters. In summary, we demonstrated varying degrees of alignment between levels of VL and gene clusters. Analyses for differential expression of genes showed genes that could be implicated in the pathogenesis of EBV-PTLD.
Allen
Upton
U
Division of Infectious Diseases, The Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. upton.allen@sickkids.ca
Barton
Michelle
M
Beyene
Joseph
J
Hu
Pingzhao
P
Khodai-Booran
Nasser
N
Hébert
Diane
D
Dipchand
Anne
A
Ng
Vicky
V
Solomon
Melinda
M
Grant
David
D
Fecteau
Annie
A
Ngan
Bo
B
Read
Stanley
S
Zielenska
Maria
M
Weitzman
Sheila
S
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000821:virology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016377:Organ Transplantation; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000821:virology*; D019562:Viral Load
D007166:Immunosuppressive Agents