Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Immunopathology Research Group, Instituto de Investigación Marqués de Vadelcilla (IDIVAL), Santander, Spain.
Front Immunol. 2024 Nov 14;15:1474271. doi: 10.3389/fimmu.2024.1474271. eCollection 2024.
Next-generation sequencing (NGS) panels are increasingly used for the diagnosis of monogenic systemic autoinflammatory diseases (SAIDs). However, their role in patients with adult-onset Still's disease (AOSD) remains unknown. This study aims to assess the usefulness of NGS panels in AOSD patients to improve diagnosis and management of the disease.
This observational, multicenter study included all patients with AOSD diagnosis who underwent NGS panel testing in northern Spain. Clinical manifestations, laboratory parameters, complications, and therapeutic responses were recorded.
A total of 24 patients (16 men, 8 women) with an average age of 42.2 ± 17.9 (mean ± SD) years, in whom NGS was performed, fulfilled the Yamaguchi and/or Fautrel criteria for AOSD. The most common symptoms, apart from fever, were skin rash (75%), asthenia (91.7%), and articular manifestations (91.7%). All patients had elevated acute-phase reactant levels and hyperferritinemia. Almost all patients received oral glucocorticoids as initial therapy. Conventional disease-modifying antirheumatic drugs (cDMARDs) were used in 17 (70.8%) patients and biologic therapy in 13 (54.1%) patients. Genetic variants were observed in 5 (20.8%) patients. None of them were classified as pathogenic. Variants of uncertain significance (VUS) were identified in (c.2104C>T and c.2251G>A), (c.224C>T), (c.1939A>C), and (c.2617G>A). Atypical manifestations and/or therapeutic refractoriness were observed in patients carrying genetic variants, except for one patient with the VUS. Four out of five patients with VUS had a severe and refractory course of the disease and required biologic therapy.
NGS was useful to rule out the presence of pathogenic genetic variants related to other SAIDs and to detect VUS that may help identify patients at risk for atypical and severe manifestations and poor response to conventional therapy.
下一代测序（NGS）面板越来越多地用于诊断单基因系统性自身炎症性疾病（SAIDs）。然而，它们在成年发病Still 病（AOSD）患者中的作用尚不清楚。本研究旨在评估 NGS 面板在 AOSD 患者中的有用性，以改善疾病的诊断和治疗。
这是一项观察性、多中心研究，纳入了在西班牙北部接受 NGS 面板检测的所有 AOSD 诊断患者。记录了临床表现、实验室参数、并发症和治疗反应。
共纳入 24 例符合 Yamaguchi 和/或 Fautrel AOSD 标准的患者（16 名男性，8 名女性），平均年龄为 42.2±17.9（均值±标准差）岁。除发热外，最常见的症状为皮疹（75%）、乏力（91.7%）和关节表现（91.7%）。所有患者均有急性期反应物水平升高和铁蛋白血症。几乎所有患者均接受口服糖皮质激素作为初始治疗。17 例（70.8%）患者接受了传统的疾病修饰抗风湿药物（cDMARDs）治疗，13 例（54.1%）患者接受了生物治疗。在 5 例（20.8%）患者中观察到遗传变异。无一例被归类为致病性。在 （c.2104C>T 和 c.2251G>A）、 （c.224C>T）、 （c.1939A>C）和 （c.2617G>A）中发现了意义不明的变异（VUS）。除了一位携带 VUS 的患者外，携带遗传变异的患者均有不典型表现和/或治疗抵抗。5 例 VUS 患者中有 4 例疾病严重且治疗反应差，需要生物治疗。
NGS 有助于排除与其他 SAIDs 相关的致病性遗传变异，并检测到 VUS，这可能有助于识别有发生不典型和严重表现以及对常规治疗反应不佳风险的患者。
