Caldirola María Soledad, Seminario Analía Gisela, Luna Paula Carolina, Curciarello Renata, Docena Guillermo Horacio, Fernandez Escobar Nicolás, Drelichman Guillermo, Gattorno Marco, de Jesus Adriana A, Goldbach-Mansky Raphaela, Gaillard María Isabel, Bezrodnik Liliana
Servicio de Inmunología, "Hospital de Niños "Dr. Ricardo Gutiérrez," Buenos Aires, Argentina.
Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP-CONICET-GCBA), Buenos Aires, Argentina.
Front Pediatr. 2023 Mar 10;11:1108207. doi: 10.3389/fped.2023.1108207. eCollection 2023.
During recent years, the identification of monogenic mutations that cause sterile inflammation has expanded the spectrum of autoinflammatory diseases, clinical disorders characterized by uncontrolled systemic and organ-specific inflammation that, in some cases, can mirror infectious conditions. Early studies support the concept of innate immune dysregulation with a predominance of myeloid effector cell dysregulation, particularly neutrophils and macrophages, in causing tissue inflammation. However, recent discoveries have shown a complex overlap of features of autoinflammation and/or immunodeficiency contributing to severe disease phenotypes. Here, we describe the first Argentine patient with a newly described frameshift mutation in c.2666delT/p.F889Sfs*2 presenting with a complex phenotypic overlap of CANDLE-like features and severe infection-induced cytopenia and immunodeficiency. The patient underwent a fully matched unrelated HSCT and has since been in inflammatory remission 5 years post-HSCT.
近年来，对导致无菌性炎症的单基因变异的鉴定拓宽了自身炎症性疾病的范畴，这类临床病症的特征是系统性和器官特异性炎症失控，在某些情况下可类似于感染性疾病。早期研究支持先天性免疫失调的概念，即髓样效应细胞失调（尤其是中性粒细胞和巨噬细胞）在引发组织炎症中占主导地位。然而，最近的发现表明，自身炎症和/或免疫缺陷的特征存在复杂的重叠，这导致了严重的疾病表型。在此，我们描述了首例阿根廷患者，该患者存在新发现的c.2666delT/p.F889Sfs*2移码突变，表现出类似CANDLE的特征与严重感染诱导的血细胞减少和免疫缺陷的复杂表型重叠。该患者接受了完全匹配的无关供者造血干细胞移植，自移植后5年以来一直处于炎症缓解状态。
