Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes

• Published in: Genes and immunity Vol. 13; no. 8; pp. 593 - 604
• Main Authors: Levy, H, Wang, X, Kaldunski, M, Jia, S, Kramer, J, Pavletich, S J, Reske, M, Gessel, T, Yassai, M, Quasney, M W, Dahmer, M K, Gorski, J, Hessner, M J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2012; Nature Publishing Group
• Subjects: 631/208/191/2018; 692/420/256; 692/53/2423; 692/699/249/1313/1418; Adolescent; Adult; Biological markers; Biomarkers; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Biosensors; Blood & organ donations; Cancer Research; Case-Control Studies; Chemokines; Chemokines - genetics; Chemokines - immunology; Chemotaxis; Chemotaxis - genetics; Chemotaxis - immunology; Child; Cryopreservation; Cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis - immunology; Cystic Fibrosis - microbiology; Cytokines; Development and progression; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diagnosis; Disease; Female; Gene Expression; Gene Expression Profiling; Genetic aspects; Genetic transcription; Genomics; Gram-positive bacteria; Human Genetics; Humans; Immunology; Infections; Inflammation - genetics; Inflammation - immunology; Influenza; Influenza A Virus, H1N1 Subtype - physiology; Influenza, Human - genetics; Influenza, Human - immunology; Influenza, Human - virology; Interleukin 1; Interleukin-1 - genetics; Interleukin-1 - immunology; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Male; Multiple sclerosis; original-article; Pathogens; Patients; Pediatrics; Peripheral blood mononuclear cells; Physiological aspects; Plasma; Pneumonia, Bacterial - genetics; Pneumonia, Bacterial - immunology; Pneumonia, Bacterial - microbiology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - physiology; Pseudomonas Infections - genetics; Pseudomonas Infections - immunology; Pseudomonas Infections - microbiology; Rheumatoid arthritis; Signal transduction; Transcription; Transcription, Genetic; Type 1 diabetes; Viral infections; United States; United States > US; Wisconsin; influenza; type 1 diabetes; gene expression profiling; biomarker; inflammation; cystic fibrosis
• ISSN: 1466-4879; 1476-5470; 1476-5470
• DOI: 10.1038/gene.2012.41

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.