Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy; DINOGMI, Università di Genova, Genoa, Italy.
Laboratory of Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Clin Immunol. 2021 Oct;231:108837. doi: 10.1016/j.clim.2021.108837. Epub 2021 Aug 26.
RAS-associated autoimmune leukoproliferative disease (RALD) is a rare immune dysregulation syndrome caused by somatic gain-of-function mutations of either NRAS or KRAS gene in hematopoietic cells. We describe a 27-year-old patient presenting at 5 months of age with recurrent infections and generalized lymphadenopathy who developed a complex multi-organ autoimmune syndrome with hypogammaglobulinemia, partially controlled with oral steroids, hydroxichloroquine, mofetil mycophenolate and IVIG prophylaxis. Activation of type I interferon pathway was observed in peripheral blood. Since 18 years of age, the patient developed regenerative nodular hyperplasia of the liver evolving into hepatopulmonary syndrome. Whole exome sequencing analysis of the peripheral blood DNA showed the NRAS p.Gly13Asp mutation validated as somatic. Our report highlights the possibility of detecting somatic NRAS gene mutations in patients with inflammatory immune dysregulation and type I interferon activation.
RAS 相关自身免疫性白细胞增生性疾病（RALD）是一种罕见的免疫失调综合征，由造血细胞中 NRAS 或 KRAS 基因的体显性获得性功能突变引起。我们描述了一位 27 岁的患者，他在 5 个月大时出现反复感染和全身淋巴结病，随后发展为复杂的多器官自身免疫综合征，伴有低丙种球蛋白血症，经口服类固醇、羟氯喹、吗替麦考酚酯和 IVIG 预防治疗部分得到控制。在外周血中观察到 I 型干扰素途径的激活。自 18 岁以来，患者出现肝再生性结节状增生，进而发展为肝肺综合征。外周血 DNA 的全外显子组测序分析显示 NRAS p.Gly13Asp 突变被确认为体细胞突变。我们的报告强调了在具有炎症性免疫失调和 I 型干扰素激活的患者中检测体细胞 NRAS 基因突变的可能性。
