Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics

Xujing Wang, Shuang Jia, Rhonda Geoffrey, Ramin Alemzadeh, Soumitra Ghosh, Martin J. Hessner

Research output: Contribution to journalArticle

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Abstract

Understanding active proinflammatory mechanisms at and before type 1 diabetes mellitus (T1DM) onset is hindered in humans, given that the relevant tissues are inaccessible and pancreatic immune responses are difficult to measure in the periphery by traditional approaches. Therefore, we investigated the use of a sensitive and comprehensive genomics strategy to investigate the presence of proinflammatory factors in serum. The sera of recent onset diabetes patients (n = 15, 12 possessing and 3 lacking islet cell autoantibodies), long-standing diabetes patients (n = 12), "at risk" siblings of diabetes patients (n = 9), and healthy controls (n = 12) were used to induce gene expression in unrelated, healthy PBMC. After culture, gene expression was measured with microarrays and normalized expression data were subjected to hierarchical clustering and multidimensional scaling. All recent onset sera induced an expression signature (192 UniGenes; fold change: >1.5, p < 0.01; false discovery rate: <0.01) that included IL-1 cytokine family members and chemokines involved in monocyte/macrophage and neutrophil chemotaxis, as well as numerous receptors and signaling molecules. This molecular signature was not induced with the sera of healthy controls or long standing diabetes patients, where longitudinal analysis of "at risk" siblings (n = 3) before and after onset support the hypothesis that the signature emerges years before onset. This study supports prior investigations of serum that reflect disease processes associated with progression to T1DM. Identification of unique inflammatory mediators may improve disease prediction beyond current islet autoantibodies. Furthermore, proinflammatory serum markers may be used as inclusion criteria or endpoint measures in clinical trials aimed at preventing T1DM.

Original languageEnglish (US)
Pages (from-to)1929-1937
Number of pages9
JournalJournal of Immunology
Volume180
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

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Genomics
Type 1 Diabetes Mellitus
Serum
Autoantibodies
Siblings
Gene Expression
Chemotaxis
Interleukin-1
Islets of Langerhans
Chemokines
Cluster Analysis
Monocytes
Neutrophils
Biomarkers
Macrophages
Clinical Trials
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics. / Wang, Xujing; Jia, Shuang; Geoffrey, Rhonda; Alemzadeh, Ramin; Ghosh, Soumitra; Hessner, Martin J.

In: Journal of Immunology, Vol. 180, No. 3, 01.02.2008, p. 1929-1937.

Research output: Contribution to journalArticle

Wang, Xujing ; Jia, Shuang ; Geoffrey, Rhonda ; Alemzadeh, Ramin ; Ghosh, Soumitra ; Hessner, Martin J. / Identification of a molecular signature in human type 1 diabetes mellitus using serum and functional genomics. In: Journal of Immunology. 2008 ; Vol. 180, No. 3. pp. 1929-1937.
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