Altare F, Lammas D, Revy P, Jouanguy E, Döffinger R, Lamhamedi S, Drysdale P, Scheel-Toellner D, Girdlestone J, Darbyshire P, Wadhwa M, Dockrell H, Salmon M, Fischer A, Durandy A, Casanova J L, Kumararatne D S
INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
J Clin Invest. 1998 Dec 15;102(12):2035-40. doi: 10.1172/JCI4950.
Interferon-gamma receptor ligand-binding chain (IFN-gammaR1) or signaling chain (IFN-gammaR2) deficiency, like interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency, predispose to severe infections due to poorly virulent mycobacteria and salmonella. A child with bacille Calmette-Guérin and Salmonella enteritidis infection was investigated. Mutations in the genes for IFN-gammaR1, IFN-gammaR2, IL-12Rbeta1, and other molecules implicated in IL-12- or IFN-gamma-mediated immunity were sought. A large homozygous deletion within the IL-12 p40 subunit gene was found, precluding expression of functional IL-12 p70 cytokine by activated dendritic cells and phagocytes. As a result, IFN-gamma production by lymphocytes was markedly impaired. This is the first discovered human disease resulting from a cytokine gene defect. It suggests that IL-12 is essential to and appears specific for protective immunity to intracellular bacteria such as mycobacteria and salmonella.
γ干扰素受体配体结合链（IFN-γR1）或信号传导链（IFN-γR2）缺陷，与白细胞介素12受体β1链（IL-12Rβ1）缺陷一样，会因致病性较弱的分枝杆菌和沙门氏菌而导致严重感染。对一名患有卡介苗和肠炎沙门氏菌感染的儿童进行了调查。研究人员寻找了IFN-γR1、IFN-γR2、IL-12Rβ1以及其他与IL-12或IFN-γ介导的免疫相关分子的基因突变。结果发现IL-12 p40亚基基因内存在一个大的纯合缺失，这使得活化的树突状细胞和吞噬细胞无法表达功能性的IL-12 p70细胞因子。因此，淋巴细胞产生的γ干扰素明显受损。这是首次发现的由细胞因子基因缺陷导致的人类疾病。这表明IL-12对于针对分枝杆菌和沙门氏菌等细胞内细菌的保护性免疫至关重要且具有特异性。
