RGD Reference Report - Switch from a dominant Th1-associated immune profile during the pre-diabetic phase in favour of a temporary increase of a Th3-associated and inflammatory immune profile at the onset of type 1 diabetes. - Rat Genome Database

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Switch from a dominant Th1-associated immune profile during the pre-diabetic phase in favour of a temporary increase of a Th3-associated and inflammatory immune profile at the onset of type 1 diabetes.

Authors: Ryden, A  Stechova, K  Durilova, M  Faresjo, M 
Citation: Ryden A, etal., Diabetes Metab Res Rev. 2009 May;25(4):335-43.
RGD ID: 2307193
Pubmed: PMID:19382103   (View Abstract at PubMed)
DOI: DOI:10.1002/dmrr.958   (Journal Full-text)

BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease dominated by loss of self-tolerance resulting in depletion of the beta-cells. This study aims to confirm previous observations of a dominant T-helper (Th)1-like profile during the period close to onset of disease. Further, to follow the immune response from onset to 2 years duration, the study focused on spontaneous as well as autoantigen-induced immune profile. METHODS: Peripheral blood mononuclear cells were collected 4 days and 1 and 2 years after diagnosis of T1D children, from healthy children carrying the human leukocyte antigen-risk genes and from high-risk children (ICA > or = 20 IJDF units). Peripheral blood mononuclear cells were stimulated with glutamic acid decarboxylase (GAD(65)) and phytohaemagglutinin (PHA). Cytokines and chemokines were detected in cell-culture supernatants by protein microarray (naive T-cells; interleukin (IL)-7, Th1; interferon-gamma, tumour necrosis factor-beta, Th2; IL-5, Th3; transforming growth factor-beta, T-regulatory cell type 1; IL-10 and inflammatory cytokines; tumour necrosis factor-alpha, IL-6 and chemokines; monocyte chemoattractant protein-1, monokine upregulated by IFN-gamma) in relation to clinical outcome (C-peptide). RESULTS: High-risk children showed a dominant Th1-associated profile with high spontaneous and GAD(65)-induced secretion. The mitogen PHA instead induced a Th2-associated response exclusively in high-risk children. In contrast, newly diagnosed T1D children showed a pronounced Th3-associated cytokine profile as well as a burst of inflammatory cytokines and chemokines secreted both spontaneously and by GAD(65) and PHA stimulation. The immune response to GAD(65) and PHA, however, diminished with duration of disease. CONCLUSION: A dominant Th1-associated immune profile was observed during the pre-diabetic phase. This Th1 dominance, however, diminished in favour of a temporary increase in a Th3-associated and inflammatory immune profile at the onset of disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 1 diabetes mellitus  IDA 2307193protein:increased expression:extracellular space (human)RGD 
type 1 diabetes mellitus  ISOIL6 (Homo sapiens)2307193; 2307193protein:increased expression:extracellular space (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il6  (interleukin 6)

Genes (Mus musculus)
Il6  (interleukin 6)

Genes (Homo sapiens)
IL6  (interleukin 6)


Additional Information