Genetically determined interferon-gamma production influences the histological phenotype of lupus nephritis.
OBJECTIVE
To clarify whether the interferon-gamma (IFN-gamma) gene (IFNG) is associated with the histological phenotype of lupus nephritis.


METHODS
We analysed microsatellite polymorphisms located within the first intron of the IFNG gene to determine the genotypes of patients with lupus nephritis WHO class IV (n=24), patients with WHO class V (n=12) and healthy controls (n=61). We used flow cytometric detection of intracellular cytokines to identify CD4(+) T cells producing IFN-gamma. Production of IFN-gamma by peripheral blood mononuclear cells after stimulation with phytohaemagglutinin was evaluated with an enzyme-linked immunosorbent assay.


RESULTS
The frequency of the IFNG allele 114 was significantly greater in WHO class V patients than in WHO class IV patients. Furthermore, the IFNG 114 +/+ genotype was more frequent in WHO class V than in WHO class IV patients. The level of IFN-gamma and the percentage of IFN-gamma-producing CD4(+) T cells were lower in individuals with genotype 114 +/+ than in individuals with genotype 114 -/-.


CONCLUSIONS
The IFN-gamma gene is associated with the histological phenotype in lupus nephritis.
Miyake
K
K
Department of Medicine and Biosystemic Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Nakashima
H
H
Akahoshi
M
M
Inoue
Y
Y
Nagano
S
S
Tanaka
Y
Y
Masutani
K
K
Hirakata
H
H
Gondo
H
H
Otsuka
T
T
Harada
M
M
D000328:Adult; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D018895:Microsatellite Repeats; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D010835:Phytohemagglutinins; D007371:Interferon-gamma; D004247:DNA