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Abstract：
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.
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.
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.
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 FAS, CASP10, TNFSF13B, LRBA, CTLA4, STAT3, IKBGK, CARD11, ADA2, and LIG4. 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.
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.
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.
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.
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 FAS, CASP10, TNFSF13B, LRBA, CTLA4, STAT3, IKBGK, CARD11, ADA2, and LIG4. 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.
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.
摘要：
Evans综合征（ES）是一种罕见的疾病，通常定义为同时或依次存在自身免疫性溶血性贫血和免疫性血小板减少症。但它也被描述为存在至少两个自身免疫性血细胞减少症。最近的报道表明，ES通常是潜在的先天性免疫错误（IEI）的表现，可以从特定的治疗中受益。
本研究的目的是调查单中心ES患者队列的临床和免疫学特征以及潜在的遗传背景。
数据来自我们中心对诊断为ES的患者的回顾性图表回顾。基因研究进行了与血液和免疫疾病相关的315个基因的NGS分析，尤其是IEI。
在1985年至2020年之间，40名患者(23名男性，研究了17名妇女），中位年龄为6岁（范围0-16）。ES在18例（45%）和22例（55%）患者中同时存在，分别。40例患者中有9例（8％）具有阳性的自身免疫家族史。在24/40(60%)和27/40(67%)的病例中存在其他异常免疫特征和淋巴增生的体征,分别。40名儿童中有17名(42%)符合ALPS诊断标准。其余21例（42％）和2例（5％）被分类为患有ALPS样和特发性疾病，分别。18名患者（45％）被发现在基因FAS上有潜在的遗传缺陷，CASP10,TNFSF13B,LRBA,CTLA4STAT3IKBGK,CARD11、ADA2和LIG4。在具有或不具有变体的患者之间以及具有经典ES的受试者与具有其他形式的多谱系血细胞减少症的受试者之间没有发现显着差异。
这项研究表明，近一半的ES患者具有遗传背景，在大多数情况下是IEI继发的。因此,应对所有患者进行分子评估。
本研究的目的是调查单中心ES患者队列的临床和免疫学特征以及潜在的遗传背景。
数据来自我们中心对诊断为ES的患者的回顾性图表回顾。基因研究进行了与血液和免疫疾病相关的315个基因的NGS分析，尤其是IEI。
在1985年至2020年之间，40名患者(23名男性，研究了17名妇女），中位年龄为6岁（范围0-16）。ES在18例（45%）和22例（55%）患者中同时存在，分别。40例患者中有9例（8％）具有阳性的自身免疫家族史。在24/40(60%)和27/40(67%)的病例中存在其他异常免疫特征和淋巴增生的体征,分别。40名儿童中有17名(42%)符合ALPS诊断标准。其余21例（42％）和2例（5％）被分类为患有ALPS样和特发性疾病，分别。18名患者（45％）被发现在基因FAS上有潜在的遗传缺陷，CASP10,TNFSF13B,LRBA,CTLA4STAT3IKBGK,CARD11、ADA2和LIG4。在具有或不具有变体的患者之间以及具有经典ES的受试者与具有其他形式的多谱系血细胞减少症的受试者之间没有发现显着差异。
这项研究表明，近一半的ES患者具有遗传背景，在大多数情况下是IEI继发的。因此,应对所有患者进行分子评估。
