患有 Evans 综合征和多系血细胞减少症患者的潜在先天性免疫缺陷：单中心分析。
Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis.
机构信息
Hematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
Unità Operativa Semplice DIpartimentale (UOSD) Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
出版信息
Front Immunol. 2022 May 17;13:869033. doi: 10.3389/fimmu.2022.869033. eCollection 2022.
BACKGROUND
Evans syndrome (ES) is a rare disorder classically defined as the simultaneous or sequential presence of autoimmune haemolytic anaemia and immune thrombocytopenia, but it has also been described as the presence of at least two autoimmune cytopenias. Recent reports have shown that ES is often a manifestation of an underlying inborn error of immunity (IEI) that can benefit from specific treatments.
AIMS
The aim of this study is to investigate the clinical and immunological characteristics and the underlying genetic background of a single-centre cohort of patients with ES.
METHODS
Data were obtained from a retrospective chart review of patients with a diagnosis of ES followed in our centre. Genetic studies were performed with NGS analysis of 315 genes related to both haematological and immunological disorders, in particular IEI.
RESULTS
Between 1985 and 2020, 40 patients (23 men, 17 women) with a median age at onset of 6 years (range 0-16) were studied. ES was concomitant and sequential in 18 (45%) and 22 (55%) patients, respectively. Nine of the 40 (8%) patients had a positive family history of autoimmunity. Other abnormal immunological features and signs of lymphoproliferation were present in 24/40 (60%) and 27/40 (67%) of cases, respectively. Seventeen out of 40 (42%) children fit the ALPS diagnostic criteria. The remaining 21 (42%) and 2 (5%) were classified as having an ALPS-like and an idiopathic disease, respectively. Eighteen patients (45%) were found to have an underlying genetic defect on genes , , , , , , , , , and . No significant differences were noted between patients with or without variant and between subjects with classical ES and the ones with other forms of multilineage cytopenias.
CONCLUSIONS
This study shows that nearly half of patients with ES have a genetic background being in most cases secondary to IEI, and therefore, a molecular evaluation should be offered to all patients.
背景
Evans 综合征 (ES) 是一种罕见疾病，经典定义为自身免疫性溶血性贫血和免疫性血小板减少症同时或序贯存在，但也有描述为至少两种自身免疫性血细胞减少症同时存在。最近的报告表明，ES 通常是潜在的先天性免疫缺陷 (IEI) 的表现，可以从特定治疗中获益。
目的
本研究旨在调查单中心队列中 ES 患者的临床和免疫学特征以及潜在的遗传背景。
方法
通过对我院确诊为 ES 的患者进行回顾性图表审查获得数据。对 315 个与血液系统和免疫性疾病相关的基因进行 NGS 分析，特别是 IEI，以进行遗传研究。
结果
在 1985 年至 2020 年间，研究了 40 名中位年龄为 6 岁（范围 0-16 岁）发病的患者（23 名男性，17 名女性）。ES 分别为同时性和序贯性，分别为 18（45%）和 22（55%）例。40 例（8%）患者有自身免疫阳性家族史。其他异常免疫特征和淋巴增殖迹象分别存在于 24/40（60%）和 27/40（67%）的病例中。40 名儿童中有 17 名（42%）符合 ALPS 诊断标准。其余 21 名（42%）和 2 名（5%）分别归类为 ALPS 样疾病和特发性疾病。18 名患者（45%）在基因、、、、、、、、和中发现潜在的遗传缺陷。在有无变异的患者之间以及在经典 ES 患者和其他多谱系血细胞减少症患者之间没有发现显著差异。
结论
本研究表明，近一半的 ES 患者有遗传背景，大多数情况下是由于 IEI，因此应向所有患者提供分子评估。
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