Use of transcriptional signatures induced in lymphoid and myeloid cell lines as an inflammatory biomarker in Type 1 diabetes

Abstract

Inflammation is common to many disorders and responsible for tissue and organ damage. In many disorders, the associated peripheral cytokine milieu is dilute and difficult to measure, necessitating development of more sensitive and informative biomarkers for mechanistic studies, earlier diagnosis, and monitoring therapeutic interventions. Previously, we have shown that plasma of recent-onset (RO) Type 1 diabetes patients induces a disease-specific proinflammatory transcriptional profile in fresh peripheral blood mononuclear cells (PBMC) compared with that of healthy controls (HC). To eliminate assay variance introduced through the use of multiple donors or multiple draws of the same person over time, we evaluated human leukemia cell lines as potential surrogates for fresh PBMC. We 1) tested seven different cell lines in their power to differentiate RO from HC plasma and 2) compared the similarity of the signatures generated across the seven cell lines to that obtained with fresh PBMC. While each cell line tested exhibited a distinct transcriptional response when cultured with RO or HC plasma, the expression profile induced in any single cell line shared little identity with that of the other cell lines or fresh PBMC. In terms of regulated biological pathways, the transcriptional response of each cell line shared varying degrees of functional identity with fresh PBMC. These results indicate that use of human leukemia cell lines as surrogates for fresh PBMC has potential in detecting perturbations to the peripheral cytokine milieu. However, the response of each is distinct, possessing varying degrees of functional relatedness to that observed with PBMC.