Department of Pediatrics, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
Pediatr Rheumatol Online J. 2023 Oct 12;21(1):117. doi: 10.1186/s12969-023-00899-4.
Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression.
We describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6.
Ruxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS.
Aicardi-Goutières 综合征（AGS）是一种罕见的遗传性早发性脑病，其特征是 I 型干扰素途径的上调，对常规免疫抑制反应不佳。
我们描述了一名 7 岁的中国男孩，他在 6 个月大时出现症状。他表现为冻疮样皮疹、白细胞减少、中性粒细胞减少、肝酶升高、生长迟缓、小头畸形、急性期反应物升高、颅内钙化和白质营养不良。3 岁时，全外显子组测序证实 IFIH1 基因存在 c.1016C > A（p.Ala339Asp）杂合功能获得性突变，诊断为 AGS7。他接受了 ruxolitinib 联合类固醇和沙利度胺治疗约四年。皮疹、血液学表现和肝功能均有所改善，但红细胞沉降率一直升高，直到添加针对白细胞介素 6 的单克隆抗体托珠单抗。
鲁索利替尼未能抑制炎症过程，托珠单抗在降低 AGS 的炎症反应方面产生了非常令人鼓舞的结果。该研究对文献做出了重要贡献，因为我们可能为 AGS 找到了一种潜在的替代治疗选择。
