Association of interferon-gamma and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes.
We studied whether serum interferon (IFN)-gamma 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 <or= 0.38 units/kg/24 h with an HbA1c <or= 7.5%. Thirty-three patients and 32 controls were phenotyped for serum concentrations of IFN-gamma and IL-10 and genotyped for functional polymorphisms of the IFN-gamma and IL-10 genes. Sixteen of 25 informative patients (63%) remitted. Serum IFN-gamma concentrations were significantly decreased in remitters but increased in non-remitters compared to controls, and did not change over time in any group. IFN-gamma genotypes corresponded with serum levels in controls and non-remitters, but not in remitters who displayed the lowest serum IFN-gamma levels despite more often carrying high-producing IFN-gamma genotypes. Neither the frequency of IL-10 genotypes nor serum IL-10 concentration differed between patients and controls. The combination of high-producing IFN-gamma genotype together with low serum IFN-gamma concentration at the time of diagnosis provided a strong positive predictive value for remission. Serum IFN-gamma 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-gamma levels. These data imply that remission is partially immune-mediated and involves regulation of IFN-gamma transcription.
Alizadeh
B Z
BZ
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, the Netherlands.
Hanifi-Moghaddam
P
P
Eerligh
P
P
van der Slik
A R
AR
Kolb
H
H
Kharagjitsingh
A V
AV
Pereira Arias
A M
AM
Ronkainen
M
M
Knip
M
M
Bonfanti
R
R
Bonifacio
E
E
Devendra
D
D
Wilkin
T
T
Giphart
M J
MJ
Koeleman
B P C
BP
Nolsøe
R
R
Mandrup Poulsen
T
T
Schloot
N C
NC
Roep
B O
BO
D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics*; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D012075:Remission, Spontaneous; D018401:Sample Size
D015415:Biomarkers; D016753:Interleukin-10; D007371:Interferon-gamma