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Specific gene expression signature associated with development of autoimmune type-I diabetes using whole-blood microarray analysis

Genes & Immunity volume 11, pages 269–278 (2010)Cite this article

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Abstract

Understanding the pathogenesis of type-I diabetes (T1D) is hindered in humans by the long autoimmune process occurring before clinical onset and by the difficulty to study the pancreas directly. Alternatively, exploring body fluids and particularly peripheral blood can provide some insights. Indeed, circulating cells can function as ‘sentinels’, with subtle changes in gene expression occurring in association with disease. Therefore, we investigated the gene expression profiles of circulating blood cells using Affymetrix microarrays. Whole-blood samples from 20 first-degree relatives of T1D children with autoimmune diabetes-related antibodies, 19 children immediately after the onset of clinical T1D and 20 age- and sex-matched healthy controls were collected in PAXgene tubes. A global gene expression analysis with MDS approach allowed the discrimination of pre-diabetic subjects, diabetic patients and healthy controls. Univariate statistical analysis highlighted 107 distinct genes differently expressed between these three groups. Two major gene expression profiles were characterized, including type-I IFN-regulated genes and genes associated with biosynthesis and oxidative phosphorylation. Our results showed the presence of early functional modifications associated with T1D, which could help to understand the disease and suggest possible avenues for therapeutic interventions.

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Acknowledgements

We thank Professors H Dodat, R Kohler and P Mouriquand, and Dr CL Gay (Hospices Civils de Lyon), Dr P Pelissier (CHU de St Etienne) and Dr C Bony (CH d’Annonay) for their contribution to the study. This work was supported by bioMérieux and grants from the ‘Association Nationale de la Recherche Technique’ (ANRT) and the ‘Association Française des diabétiques’ (AFD).

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Authors and Affiliations

  1. Joint Unit Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Herriot, Lyon, France

    F Reynier, A Pachot, M Paye, F Turrel-Davin, F Petit, A Hot & B Mougin

  2. Fudan University Cancer Hospital-bioMérieux Laboratory, Shanghai, China

    Q Xu

  3. Functional Genomics and Systems Biology for Health, CNRS Institute of Biological Sciences, Villejuif, France

    C Auffray

  4. Division of Pediatric Endocrinology and Diabetology, Hôpital Femme-Mère-Enfant, Lyon, France

    N Bendelac & M Nicolino

  5. Department of Endocrinology and Diabetes, Hôpital Edouard Herriot, HCL Lyon, France

    C Thivolet

  6. INSERM, U870; INRA, U1235; INSA-Lyon, RMND; University Lyon 1,

    M Nicolino & C Thivolet

  7. INRA, U1235, France

    M Nicolino & C Thivolet

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  1. F Reynier
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Correspondence to F Reynier.

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Reynier, F., Pachot, A., Paye, M. et al. Specific gene expression signature associated with development of autoimmune type-I diabetes using whole-blood microarray analysis. Genes Immun 11, 269–278 (2010). https://doi.org/10.1038/gene.2009.112

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  • DOI: https://doi.org/10.1038/gene.2009.112

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