Hong Soon-Min, Chen Wei, Feng Jiaqi, Dai Dai, Shen Nan
Shanghai Institute of Rheumatology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Rheumatology, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Front Pediatr. 2022 May 13;10:885006. doi: 10.3389/fped.2022.885006. eCollection 2022.
The study of genetic predisposition to pediatric systemic lupus erythematosus (pSLE) has brought new insights into the pathophysiology of SLE, as it is hypothesized that genetic predisposition is greater in children. Furthermore, identifying genetic variants and linking disrupted genes to abnormal immune pathways and clinical manifestations can be beneficial for both diagnosis and treatment. Here, we identified genetic alterations in a patient with childhood-onset SLE and analyzed the immunological mechanisms behind them to support future diagnosis, prognosis, and treatment.
Whole exome sequencing (WES) was adopted for genetic analysis of a patient with childhood-onset SLE. Gene mutations were confirmed by Sanger sequencing. Clinical data of this patient were collected and summarized. Ingenuity Pathway Analysis was used to provide interacting genes of the perturbed genes. Online Enrichr tool and Cytoscape software were used to analysis the related pathways of these genes.
We present a case of a 2-year-old girl who was diagnosed with idiopathic thrombocytopenic purpura (ITP) and SLE. The patient was characterized by cutaneous bleeding spots on both lower extremities, thrombocytopenia, decreased serum complements levels, increased urinary red blood cells, and positive ANA and dsDNA. The patient was treated with methylprednisolone and mycophenolate, but clinical remission could not be achieved. The genomic analysis identified three novel mutations in this pSLE patient, a double-stranded missense mutation in ACP5 (c.1152G>T and c.420G>A) and a single-stranded mutation in SAMHD1 (c.1423G>A). Bioinformatic analysis showed that these two genes and their interacting genes are enriched in the regulation of multiple immune pathways associated with SLE, including cytokine signaling and immune cell activation or function. Analysis of the synergistic regulation of these two genes suggests that abnormalities in the type I interferon pathway caused by genetic variants may contribute to the pathogenesis of SLE.
The combined complexity of polymorphisms in the coding regions of ACP5 and SAMHD1 influences the susceptibility to SLE. Alterations in these genes may lead to abnormalities in the type I interferon pathway. Our study extends the spectrum of mutations in the ACP5 and SAMHD1 genes. The identification of these mutations could aid in the diagnosis of SLE with genetic counseling and suggest potential precise treatments for specific pathways.
儿童系统性红斑狼疮（pSLE）遗传易感性的研究为系统性红斑狼疮（SLE）的病理生理学带来了新的见解，因为据推测儿童的遗传易感性更高。此外，识别基因变异并将受干扰的基因与异常免疫途径和临床表现联系起来，对诊断和治疗都有益处。在此，我们鉴定了一名儿童期起病的SLE患者的基因改变，并分析了其背后的免疫机制，以支持未来的诊断、预后和治疗。
采用全外显子组测序（WES）对一名儿童期起病的SLE患者进行基因分析。通过Sanger测序确认基因突变。收集并总结该患者的临床资料。使用Ingenuity Pathway Analysis提供受干扰基因的相互作用基因。使用在线Enrichr工具和Cytoscape软件分析这些基因的相关途径。
我们报告了一例2岁女孩，她被诊断为特发性血小板减少性紫癜（ITP）和SLE。该患者的特征为双下肢皮肤出血点、血小板减少、血清补体水平降低、尿红细胞增多，以及抗核抗体（ANA）和双链DNA（dsDNA）阳性。患者接受了甲泼尼龙和霉酚酸酯治疗，但未实现临床缓解。基因组分析在这名pSLE患者中鉴定出三个新突变，分别为酸性磷酸酶5（ACP5）基因的一个双链错义突变（c.1152G>T和c.420G>A）以及含SAM结构域的组氨酸脱甲基酶1（SAMHD1）基因的一个单链突变（c.1423G>A）。生物信息学分析表明，这两个基因及其相互作用基因在与SLE相关的多种免疫途径的调节中富集，包括细胞因子信号传导以及免疫细胞激活或功能。对这两个基因协同调节的分析表明，基因变异导致的I型干扰素途径异常可能促成了SLE的发病机制。
ACP5和SAMHD1编码区多态性的综合复杂性影响了对SLE的易感性。这些基因的改变可能导致I型干扰素途径异常。我们的研究扩展了ACP5和SAMHD1基因的突变谱。识别这些突变有助于通过遗传咨询诊断SLE，并为特定途径提示潜在的精准治疗方法。
