Faculty Collaboration Database

Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes. Genes Immun 2012 Dec;13(8):593-604

Date

09/14/2012

Pubmed ID

22972474

Pubmed Central ID

PMC4265236

DOI

10.1038/gene.2012.41

Scopus ID

2-s2.0-84870911405 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding therapeutic decisions and monitoring interventions. We previously demonstrated that plasma samples from recent-onset type 1 diabetes (RO T1D) patients induce a proinflammatory transcriptional signature in freshly drawn peripheral blood mononuclear cells (PBMCs) relative to that of unrelated healthy controls (HC). Here, using cryopreserved PBMC, we analyzed larger RO T1D and HC cohorts, examined T1D progression in pre-onset samples, and compared the RO T1D signature to those associated with three disorders characterized by airway infection and inflammation. The RO T1D signature, consisting of interleukin-1 cytokine family members, chemokines involved in immunocyte chemotaxis, immune receptors and signaling molecules, was detected during early pre-diabetes and found to resolve post-onset. The signatures associated with cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, patients with confirmed bacterial pneumonia, and subjects with H1N1 influenza all reflected immunological activation, yet each were distinct from one another and negatively correlated with that of T1D. This study highlights the remarkable capacity of cells to serve as biosensors capable of sensitively and comprehensively differentiating immunological states.

Author List

Levy H, Wang X, Kaldunski M, Jia S, Kramer J, Pavletich SJ, Reske M, Gessel T, Yassai M, Quasney MW, Dahmer MK, Gorski J, Hessner MJ

Author

Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Biomarkers
Case-Control Studies
Chemokines
Chemotaxis
Child
Cystic Fibrosis
Diabetes Mellitus, Type 1
Female
Gene Expression Profiling
Humans
Inflammation
Influenza A Virus, H1N1 Subtype
Influenza, Human
Interleukin-1
Leukocytes, Mononuclear
Male
Pneumonia, Bacterial
Pseudomonas Infections
Pseudomonas aeruginosa
Transcription, Genetic