Cattalini Marco, Galli Jessica, Zunica Fiammetta, Ferraro Rosalba Monica, Carpanelli Marialuisa, Orcesi Simona, Palumbo Giovanni, Pinelli Lorenzo, Giliani Silvia, Fazzi Elisa, Badolato Raffaele
Pediatrics Clinic, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia, Brescia, Italy.
Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy.
Front Pediatr. 2021 Oct 27;9:725868. doi: 10.3389/fped.2021.725868. eCollection 2021.
Type I Interferonopathies comprise inherited inflammatory diseases associated with perturbation of the type I IFN response. Use of kinase (JAK) inhibitors has been recently reported as possible tools for treating some of those rare diseases. We describe herein the clinical picture and treatment response to the JAK-inhibitor ruxolitinib in a 5-year-old girl affected by Aicardi-Goutières Syndrome type 6 (AGS6) due to mutation. The girl's interferon score (IS) was compared with that of her older brother, suffering from the same disorder, who was not treated. We observed a limited, but distinct neurological improvement (Gross Motor Function and Griffiths Mental Development Scales). Analysis of IS values of the two siblings during the treatment showed several changes, especially related to infections; the IS values of the child treated with ruxolitinib were consistently lower than those measured in her brother. Based on these observations we suggest that the use of ruxolitinib in children with the same condition might be effective in inhibiting type I interferon response and that starting this therapy at early age in children with AGS could mitigate the detrimental effects of type I interferon hyperproduction.
I型干扰素病包括与I型干扰素反应紊乱相关的遗传性炎症性疾病。最近有报道称，使用激酶（JAK）抑制剂可能是治疗其中一些罕见疾病的手段。我们在此描述了一名5岁患有6型Aicardi-Goutières综合征（AGS6）的女孩因 突变而对JAK抑制剂鲁索替尼的临床表现和治疗反应。将该女孩的干扰素评分（IS）与其患有相同疾病但未接受治疗的哥哥的评分进行了比较。我们观察到有有限但明显的神经功能改善（粗大运动功能和格里菲斯心理发展量表）。治疗期间对两兄妹IS值的分析显示出一些变化，特别是与感染有关的变化；接受鲁索替尼治疗的儿童的IS值始终低于其哥哥的测量值。基于这些观察结果，我们认为在患有相同病症的儿童中使用鲁索替尼可能有效地抑制I型干扰素反应，并且在AGS儿童早期开始这种治疗可以减轻I型干扰素过度产生的有害影响。
