Tanaka Y, Nakashima H, Hisano C, Kohsaka T, Nemoto Y, Niiro H, Otsuka T, Otsuka T, Imamura T, Niho Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Immunogenetics. 1999 Apr;49(4):266-71. doi: 10.1007/s002510050492.
Genetic factors seem to play a significant role in susceptibility to systemic lupus erythematosus (SLE). The purpose of this study was to investigate whether the amino acid polymorphism (Val14Met) found within the IFN-gamma receptor gene (IFNGR1) plays a prominent role in susceptibility to SLE. We found Val14Met located at the COOH terminal of the signal peptide of the IFN-gamma receptor. There was a significant difference in this polymorphism frequency between SLE patients and healthy populations. To clarify whether this amino acid substitution resulted in the alteration of the receptor function, we evaluated the induction of HLA-DR antigen expression on B cells by IFN-gamma stimulation. There was also a significant difference in the induction of HLA-DR by IFN-gamma stimulation between B cells. Furthermore, an intracellular cytokine assay indicated that the Th1/Th2 balance of Th cells bearing the variant receptor shifted to Th2. The genetic polymorphism found within the IFN-gamma receptor gene (Val14Met) may result in a shift to Th2, and this shift may increase susceptibility to SLE.
遗传因素似乎在系统性红斑狼疮（SLE）易感性中起重要作用。本研究的目的是调查在干扰素-γ受体基因（IFNGR1）中发现的氨基酸多态性（Val14Met）是否在SLE易感性中起显著作用。我们发现Val14Met位于干扰素-γ受体信号肽的COOH末端。SLE患者与健康人群之间这种多态性频率存在显著差异。为了阐明这种氨基酸替代是否导致受体功能改变，我们通过干扰素-γ刺激评估了B细胞上HLA-DR抗原表达的诱导情况。B细胞之间干扰素-γ刺激诱导HLA-DR表达也存在显著差异。此外，细胞内细胞因子检测表明，携带变异受体的Th细胞的Th1/Th2平衡向Th2偏移。在干扰素-γ受体基因中发现的遗传多态性（Val14Met）可能导致向Th2偏移，这种偏移可能增加SLE易感性。
