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

Genes & Immunity volume 13, pages 593–604 (2012)Cite this article

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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.

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Acknowledgements

We thank the patients and families who participated in this study. We acknowledge the physicians, nurses and staff of Children’s Hospital of Wisconsin and The Max McGee National Research Center for Juvenile Diabetes who assisted in subject recruitment and sample collection/processing. This work was supported by the Juvenile Diabetes Research Foundation International (1-2008-1026 and 5-2012-220 to MJH); the National Institutes of Health (R01AI078713 to MJH, DP2OD007031 to HL, R01DK080100 to XW, U19AI062627 to JG and 1-UL1-RR031973 the Clinical and Translational Science Institute of Southeast Wisconsin); Genentech (IST grant to HL); and The Children’s Hospital of Wisconsin Foundation.

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  1. H Levy and X Wang: Joint first authors.

Authors and Affiliations

  1. The Department of Pediatrics, The Medical College of Wisconsin, Milwaukee, WI, USA

    H Levy, M Kaldunski, S Jia, J Kramer, S J Pavletich, M Reske, T Gessel, M W Quasney, M K Dahmer & M J Hessner

  2. The Children’s Research Institute, Children’s Hospital of Wisconsin, Milwaukee, WI, USA

    H Levy, M Kaldunski, S Jia, J Kramer, S J Pavletich, M Reske, T Gessel, M W Quasney, M K Dahmer & M J Hessner

  3. The Department of Physics, The Comprehensive Diabetes Center, The University of Alabama-Birmingham, Birmingham, AL, USA

    X Wang

  4. The Max McGee National Research Center for Juvenile Diabetes, The Medical College of Wisconsin, Milwaukee, WI, USA

    M Kaldunski, S Jia, J Kramer, S J Pavletich & M J Hessner

  5. Molecular Genetics Laboratory, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA

    M Yassai & J Gorski

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Levy, H., Wang, X., Kaldunski, M. et al. Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes. Genes Immun 13, 593–604 (2012). https://doi.org/10.1038/gene.2012.41

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