PMID- 17659059
OWN - NLM
STAT- MEDLINE
DCOM- 20071019
LR  - 20181201
IS  - 1399-543X (Print)
IS  - 1399-543X (Linking)
VI  - 8
IP  - 4
DP  - 2007 Aug
TI  - The importance of CTLA-4 polymorphism and human leukocyte antigen genotype for 
      the induction of diabetes-associated cytokine response in healthy school 
      children.
PG  - 185-92
AB  - BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease associated with the 
      destruction of pancreatic beta cells and genetically linked to human leukocyte 
      antigen (HLA) class II DR3-DQ2 and DR4-DQ8 haplotypes. The +49A/G polymorphism of 
      the immunoregulatory cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene is also 
      associated with T1D. Genetic and environmental risk factors precede the onset of 
      T1D, which is characterized by a T helper 1 cell-dominating cytokine response to 
      diabetes-related autoantigens. AIM: To investigate immunological differences 
      between healthy children with and without CTLA-4 +49A/G and HLA genetic 
      susceptibility for T1D. STUDY DESIGN: Young, 7-15 years of age, healthy subjects 
      (n = 58) were investigated to test whether CTLA-4 +49A/G genotype was associated 
      with enzyme-linked immunospot assay T-cell responses to T1D-related autoantigens. 
      Because T1D is primarily HLA-DQ associated, we stratified the healthy subjects by 
      HLA genotypes associated with the disease. RESULTS: Peptide of heat shock protein 
      60 induced a higher interferon-gamma (IFN-gamma) response in subjects with 
      risk-associated CTLA-4 polymorphism (GG genotype) (p = 0.02) while glutamic acid 
      decarboxylase 65-induced interleukin-4 (IL-4) secretion was lower in GG genotype 
      subjects (p = 0.02). CONCLUSION: The increased IFN-gamma response and lower IL-4 
      response toward diabetes-related autoantigens shown in CTLA-4 +49 GG risk 
      subjects show a possible mechanism for the association between CTLA-4 and T1D.
FAU - Jonson, Carl-Oscar
AU  - Jonson CO
AD  - Division of Pediatrics and Diabetes Research Centre, Department of Molecular and 
      Clinical Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, 
      Sweden. carl-oscar.jonson@imk.liu.se
FAU - Lernmark, Ake
AU  - Lernmark A
FAU - Ludvigsson, Johnny
AU  - Ludvigsson J
FAU - Rutledge, Elizabeth A
AU  - Rutledge EA
FAU - Hinkkanen, Ari
AU  - Hinkkanen A
FAU - Faresjo, Maria
AU  - Faresjo M
LA  - eng
GR  - DK 17047/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Chaperonin 60)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQbeta antigen)
RN  - 0 (IL4 protein, human)
RN  - 0 (Insulin Antibodies)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adolescent
MH  - Antigens, CD/*genetics
MH  - Antigens, Differentiation/*genetics
MH  - CTLA-4 Antigen
MH  - Chaperonin 60
MH  - Child
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Glutamate Decarboxylase/analysis
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ beta-Chains
MH  - Humans
MH  - Insulin Antibodies/analysis
MH  - Interferon-gamma/*metabolism
MH  - Interleukin-4/*metabolism
MH  - Leukocytes, Mononuclear/immunology
MH  - Male
MH  - *Polymorphism, Genetic
MH  - Polymorphism, Restriction Fragment Length
EDAT- 2007/07/31 09:00
MHDA- 2007/10/20 09:00
CRDT- 2007/07/31 09:00
PHST- 2007/07/31 09:00 [pubmed]
PHST- 2007/10/20 09:00 [medline]
PHST- 2007/07/31 09:00 [entrez]
AID - PDI245 [pii]
AID - 10.1111/j.1399-5448.2007.00245.x [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2007 Aug;8(4):185-92. doi: 10.1111/j.1399-5448.2007.00245.x.