Back to Search Start Over

Association of interferon-γ and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes

Authors :
Pejman Hanifi-Moghaddam
Bart O. Roep
Hubert Kolb
A. V. Kharagjitsingh
P. Eerligh
Matti S Ronkainen
Mikael Knip
D. Devendra
A. R. van der Slik
Riccardo Bonfanti
Bobby P. C. Koeleman
Behrooz Alizadeh
A. M. Pereira Arias
T. Mandrup Poulsen
R. Nolsoe
Ezio Bonifacio
Terence J. Wilkin
Nanette C. Schloot
Marius J. Giphart
Alizadeh, Bz
Hanifi-Moghaddam, P
Eerligh, P
van der Slik, Ar
Kolb, H
Kharagjitsingh, Av
Arias, Amp
Ronkainen, M
Knip, M
Bonfanti, R
Bonifacio, E
Devendra, D
Wilkin, T
Giphart, Mj
Koeleman, Bpc
Nolsoe, R
Poulsen, Tm
Schloot, Nc
Roep, Bo
Life Course Epidemiology
Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Groningen Institute for Gastro Intestinal Genetics and Immunology
Source :
Clinical and Experimental Immunology. Wiley
Publication Year :
2006
Publisher :
Blackwell Science Inc, 2006.

Abstract

Summary We studied whether serum interferon (IFN)-γ or interleukin (IL)-10 levels and their corresponding functional polymorphic genotypes are associated with partial remission of type 1 diabetes (T1D). A multi-centre study was undertaken in patients with newly diagnosed T1D and matched controls. T1D patients were followed for 3 months and characterized for remission status. Partial clinical remission was defined as a daily insulin dose ≤ 0.38 units/kg/24 h with an HbA1c ≤ 7.5%. Thirty-three patients and 32 controls were phenotyped for serum concentrations of IFN-γ and IL-10 and genotyped for functional polymorphisms of the IFN-γ and IL-10 genes. Sixteen of 25 informative patients (63%) remitted. Serum IFN-γ concentrations were significantly decreased in remitters but increased in non-remitters compared to controls, and did not change over time in any group. IFN-γ genotypes corresponded with serum levels in controls and non-remitters, but not in remitters who displayed the lowest serum IFN-γ levels despite more often carrying high-producing IFN-γ genotypes. Neither the frequency of IL-10 genotypes nor serum IL-10 concentration differed between patients and controls. The combination of high-producing IFN-γ genotype together with low serum IFN-γ concentration at the time of diagnosis provided a strong positive predictive value for remission. Serum IFN-γ concentrations predicted by genotype and observed serum levels were discordant in remitters, suggestive of regulation overruling genetic predisposition. Although high-producing genotypes were less frequent in remitters, they were predictive of remission in combination with low serum IFN-γ levels. These data imply that remission is partially immune-mediated and involves regulation of IFN-γ transcription.

Details

Language :
English
ISSN :
00099104
Database :
OpenAIRE
Journal :
Clinical and Experimental Immunology. Wiley
Accession number :
edsair.doi.dedup.....1731e4d6f809048aae4718f368598edc