PDF(Pubmed)
Abstract：
Inborn errors of immunity (IEI) are genetic disorders characterized by a wide spectrum of clinical manifestations, ranging from increased susceptibility to infections to significant immune dysregulation. Among these, primary immune regulatory disorders (PIRDs) are mainly presenting with autoimmune manifestations, and autoimmune cytopenias (AICs) can be the first clinical sign. Significantly, AICs in patients with IEI often fail to respond to first-line therapy. In pediatric patients, autoimmune cytopenias can be red flags for IEI. However, for these cases precise indicators or parameters useful to suspect and screen for a hidden congenital immune defect are lacking. Therefore, we focused on chronic/refractory AIC patients to perform an extensive clinical evaluation and multiparametric flow cytometry analysis to select patients in whom PIRD was strongly suspected as candidates for genetic analysis. Key IEI-associated alterations causative of STAT3 GOF disease, IKAROS haploinsufficiency, activated PI3Kδ syndrome (APDS), Kabuki syndrome and autoimmune lymphoproliferative syndrome (ALPS) were identified. In this scenario, a dysregulated immunophenotype acted as a potential screening tool for an early IEI diagnosis, pivotal for appropriate clinical management and for the identification of new therapeutic targets.
摘要：
先天性免疫错误（IEI）是一种遗传性疾病，具有广泛的临床表现，从对感染的易感性增加到显著的免疫失调。其中,原发性免疫调节疾病（PIRD）主要表现为自身免疫表现，自身免疫性血细胞减少症（AIC）可能是第一个临床体征。重要的是,IEI患者的AIC通常对一线治疗没有反应。在儿科患者中，自身免疫性血细胞减少可能是IEI的危险信号。然而,对于这些情况，缺乏可用于怀疑和筛查隐藏的先天性免疫缺陷的精确指标或参数。因此,我们专注于慢性/难治性AIC患者进行广泛的临床评估和多参数流式细胞术分析,以选择强烈怀疑PIRD为基因分析候选对象的患者.STAT3GOF疾病的关键IEI相关改变，IKAROS单倍体功能不全,活化PI3Kδ综合征（APDS），确定了歌舞uki综合征和自身免疫性淋巴增生综合征（ALPS）。在这种情况下，失调的免疫表型作为早期IEI诊断的潜在筛选工具，对于适当的临床管理和确定新的治疗靶点至关重要。
