From biomarkers to a clue of biology: A computation-aided perspective of immune gene expression profiles in human type 1 diabetes

Dongmei Han, Xiaodong Cai, Ji Wen, Norma S Kenyon, Zhibin Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Dysregulated expression of key immune genes may cause breakdown of immunologi-cal tolerance and development of autoimmune disorders such as type 1 diabetes (T1D). General immune insufficiencies have also been implicated as a trigger of autoimmunity, due to their potential impact on immune homeostasis. Recent studies have detected evidence of systemic reduction in immune gene expression in long-term diabetic patients but the changes were not present before or atT1D onset. The changes could not be merely correlated with alteration in metabolic parameters. The studies also identified a dynamic expression pattern of several well-known as well as little-studied, immune-related genes during the course of T1D. An intriguing "ratio profile" of immune regulatory genes, such as CTLA4 and members of the S100 family, versus "baseline" immune genes, such as CD3G, prompted us to further examine immune gene expression relationships for a set of molecules representing T cells, B cells, and myeloid cells. No evidence was found to suggest an overall breach of tolerance equilibrium in T1D. Perplexingly, patients with long-term T1D presented a gene expression profile that was surprisingly more coordinated in analyses of "networking" relationship. Computational analyses of the "ratio profiles" or "relationship profiles" of immune gene expression might provide a clue for further studies of immunobiology in human T1D and other autoimmune diseases, as to how the profiles may be related to the pathogenic cause of the disease, to the effect of the diseases on immune homeostasis, or to an immunological process associated with the course of the diseases but is neither a direct cause nor a direct effect of the diseases.

Original languageEnglish
Article numberArticle 320
JournalFrontiers in Immunology
Volume3
Issue numberOCT
DOIs
StatePublished - Dec 1 2012

Fingerprint

Type 1 Diabetes Mellitus
Transcriptome
Biomarkers
Homeostasis
Genes
Gene Expression
Immune System Diseases
Myeloid Cells
Regulator Genes
Autoimmunity
Autoimmune Diseases
B-Lymphocytes
T-Lymphocytes

Keywords

  • Autoimmunity
  • Computation
  • Diabetes
  • Gene expression
  • Human

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

@article{e372468ec4444ed7bb5934154a2bb0f9,
title = "From biomarkers to a clue of biology: A computation-aided perspective of immune gene expression profiles in human type 1 diabetes",
abstract = "Dysregulated expression of key immune genes may cause breakdown of immunologi-cal tolerance and development of autoimmune disorders such as type 1 diabetes (T1D). General immune insufficiencies have also been implicated as a trigger of autoimmunity, due to their potential impact on immune homeostasis. Recent studies have detected evidence of systemic reduction in immune gene expression in long-term diabetic patients but the changes were not present before or atT1D onset. The changes could not be merely correlated with alteration in metabolic parameters. The studies also identified a dynamic expression pattern of several well-known as well as little-studied, immune-related genes during the course of T1D. An intriguing {"}ratio profile{"} of immune regulatory genes, such as CTLA4 and members of the S100 family, versus {"}baseline{"} immune genes, such as CD3G, prompted us to further examine immune gene expression relationships for a set of molecules representing T cells, B cells, and myeloid cells. No evidence was found to suggest an overall breach of tolerance equilibrium in T1D. Perplexingly, patients with long-term T1D presented a gene expression profile that was surprisingly more coordinated in analyses of {"}networking{"} relationship. Computational analyses of the {"}ratio profiles{"} or {"}relationship profiles{"} of immune gene expression might provide a clue for further studies of immunobiology in human T1D and other autoimmune diseases, as to how the profiles may be related to the pathogenic cause of the disease, to the effect of the diseases on immune homeostasis, or to an immunological process associated with the course of the diseases but is neither a direct cause nor a direct effect of the diseases.",
keywords = "Autoimmunity, Computation, Diabetes, Gene expression, Human",
author = "Dongmei Han and Xiaodong Cai and Ji Wen and Kenyon, {Norma S} and Zhibin Chen",
year = "2012",
month = "12",
day = "1",
doi = "10.3389/fimmu.2012.00320",
language = "English",
volume = "3",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
number = "OCT",

}

TY - JOUR

T1 - From biomarkers to a clue of biology

T2 - A computation-aided perspective of immune gene expression profiles in human type 1 diabetes

AU - Han, Dongmei

AU - Cai, Xiaodong

AU - Wen, Ji

AU - Kenyon, Norma S

AU - Chen, Zhibin

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Dysregulated expression of key immune genes may cause breakdown of immunologi-cal tolerance and development of autoimmune disorders such as type 1 diabetes (T1D). General immune insufficiencies have also been implicated as a trigger of autoimmunity, due to their potential impact on immune homeostasis. Recent studies have detected evidence of systemic reduction in immune gene expression in long-term diabetic patients but the changes were not present before or atT1D onset. The changes could not be merely correlated with alteration in metabolic parameters. The studies also identified a dynamic expression pattern of several well-known as well as little-studied, immune-related genes during the course of T1D. An intriguing "ratio profile" of immune regulatory genes, such as CTLA4 and members of the S100 family, versus "baseline" immune genes, such as CD3G, prompted us to further examine immune gene expression relationships for a set of molecules representing T cells, B cells, and myeloid cells. No evidence was found to suggest an overall breach of tolerance equilibrium in T1D. Perplexingly, patients with long-term T1D presented a gene expression profile that was surprisingly more coordinated in analyses of "networking" relationship. Computational analyses of the "ratio profiles" or "relationship profiles" of immune gene expression might provide a clue for further studies of immunobiology in human T1D and other autoimmune diseases, as to how the profiles may be related to the pathogenic cause of the disease, to the effect of the diseases on immune homeostasis, or to an immunological process associated with the course of the diseases but is neither a direct cause nor a direct effect of the diseases.

AB - Dysregulated expression of key immune genes may cause breakdown of immunologi-cal tolerance and development of autoimmune disorders such as type 1 diabetes (T1D). General immune insufficiencies have also been implicated as a trigger of autoimmunity, due to their potential impact on immune homeostasis. Recent studies have detected evidence of systemic reduction in immune gene expression in long-term diabetic patients but the changes were not present before or atT1D onset. The changes could not be merely correlated with alteration in metabolic parameters. The studies also identified a dynamic expression pattern of several well-known as well as little-studied, immune-related genes during the course of T1D. An intriguing "ratio profile" of immune regulatory genes, such as CTLA4 and members of the S100 family, versus "baseline" immune genes, such as CD3G, prompted us to further examine immune gene expression relationships for a set of molecules representing T cells, B cells, and myeloid cells. No evidence was found to suggest an overall breach of tolerance equilibrium in T1D. Perplexingly, patients with long-term T1D presented a gene expression profile that was surprisingly more coordinated in analyses of "networking" relationship. Computational analyses of the "ratio profiles" or "relationship profiles" of immune gene expression might provide a clue for further studies of immunobiology in human T1D and other autoimmune diseases, as to how the profiles may be related to the pathogenic cause of the disease, to the effect of the diseases on immune homeostasis, or to an immunological process associated with the course of the diseases but is neither a direct cause nor a direct effect of the diseases.

KW - Autoimmunity

KW - Computation

KW - Diabetes

KW - Gene expression

KW - Human

UR - http://www.scopus.com/inward/record.url?scp=84874218779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874218779&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2012.00320

DO - 10.3389/fimmu.2012.00320

M3 - Article

C2 - 23112798

AN - SCOPUS:84874218779

VL - 3

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - OCT

M1 - Article 320

ER -