Understanding gene expression patterns in immune-mediated disorders

Gene expression profiling of peripheral blood cells can provide dynamic information regarding the host response to immune-mediated disorders. AlloMap molecular expression testing from XDx monitors the expression of 20 genes in peripheral blood mononuclear cells (PBMC) to discriminate cardiac allograft recipients of 15 years or greater who are at low risk for acute cellular rejection (ACR). The AlloMap test classifier is based on the expression level of 11 genes, encoding proteins with diverse functions, which are differentially expressed in stable patients with moderate to severe ACR compared to patients without ACR. The nine other test genes are used for normalizing gene expression levels and assuring sample quality. In this work we review the development processes leading to the selection of the 11 informative genes and the derivation of the AlloMap test classifier, and discuss the relationship of peripheral blood gene expression with diverse pathways associated with ACR, including T-cell priming, platelet activation, systemic responses to allograft inflammation, and the overall state of immunosuppression.