Wang Ben X, Grover Stephanie A, Kannu Peter, Yoon Grace, Laxer Ronald M, Yeh E Ann, Fish Eleanor N
1 Toronto General Research Institute, University Health Network , Toronto, Ontario, Canada .
2 Department of Immunology, University of Toronto , Toronto, Ontario, Canada .
J Interferon Cytokine Res. 2017 Apr;37(4):147-152. doi: 10.1089/jir.2016.0117. Epub 2017 Feb 17.
Aicardi-Goutières syndrome (AGS) is an early-onset, genetic disease characterized by recurrent fever, multifocal lesions of the brain, and systemic autoimmunity. We report on 3 AGS patients, 2 siblings with an RNASEH2A gene mutation and 1 patient with a SAMHD1 gene mutation. Serial analysis of peripheral blood from all 3 AGS patients showed consistently elevated expression of the interferon-stimulated genes (ISGs): ISG15, RSAD2, and IFI27, not observed in unaffected family members. Enumeration of circulating white blood cells and platelets and examination of C-reactive protein showed no significant deviation from the normal range for Patient 2 with the RNASEH2A mutation and Patient 3 with the SAMHD1 mutation, even when Patient 2 had magnetic resonance imaging abnormalities and ongoing febrile episodes. Erythrocyte sedimentation rates fluctuated within the normal range for Patient 2, with some elevation, yet, were in the normal range during the second febrile episode when there were accompanying neurological abnormalities. These preliminary data suggest that ISG expression may be a more specific indicator of disease activity in comparison to standard inflammatory markers.
艾卡迪-古铁雷斯综合征（AGS）是一种早发性遗传病，其特征为反复发热、脑部多灶性病变和全身自身免疫。我们报告了3例AGS患者，2例携带RNASEH2A基因突变的同胞以及1例携带SAMHD1基因突变的患者。对所有3例AGS患者外周血的系列分析显示，干扰素刺激基因（ISG）：ISG15、RSAD2和IFI27的表达持续升高，而在未受影响的家庭成员中未观察到这种情况。对携带RNASEH2A基因突变的患者2和携带SAMHD1基因突变的患者3进行循环白细胞和血小板计数以及C反应蛋白检查，结果显示与正常范围无显著偏差，即使患者2有磁共振成像异常且持续发热。患者2的红细胞沉降率在正常范围内波动，有一定程度升高，但在第二次发热发作伴有神经异常时仍在正常范围内。这些初步数据表明，与标准炎症标志物相比，ISG表达可能是疾病活动更特异的指标。
