PDF(Pubmed)
Abstract：
Haploinsufficiency of suppressor of cytokine signaling 1 (SOCS1) is a recently discovered autoinflammatory disorder with significant rheumatologic, immunologic, and hematologic manifestations. Here we report a case of SOCS1 haploinsufficiency in a 5-year-old child with profound arthralgias and immune-mediated thrombocytopenia unmasked by SARS-CoV-2 infection. Her clinical manifestations were accompanied by excessive B cell activity, eosinophilia, and elevated IgE levels. Uniquely, this is the first report of SOCS1 haploinsufficiency in the setting of a chromosomal deletion resulting in complete loss of a single SOCS1 gene with additional clinical findings of bone marrow hypocellularity and radiologic evidence of severe enthesitis. Immunologic profiling showed a prominent interferon signature in the patient\'s peripheral blood mononuclear cells, which were also hypersensitive to stimulation by type I and type II interferons. The patient showed excellent clinical and functional laboratory response to tofacitinib, a Janus kinase inhibitor that disrupts interferon signaling. Our case highlights the need to utilize a multidisciplinary diagnostic approach and consider a comprehensive genetic evaluation for inborn errors of immunity in patients with an atypical immune-mediated thrombocytopenia phenotype.
摘要：
细胞因子信号抑制因子1（SOCS1）的单倍功能不全是一种最近发现的自身炎症性疾病，具有重要的风湿病，免疫学,和血液学表现。在这里，我们报告了一例SOCS1单倍功能不全的5岁儿童，患有严重的关节痛和由SARS-CoV-2感染掩盖的免疫介导的血小板减少症。她的临床表现伴有过度的B细胞活动，嗜酸性粒细胞增多,IgE水平升高。独特的,这是在染色体缺失导致单个SOCS1基因完全缺失的情况下SOCS1单倍体功能不全的首例报告,并有更多的临床发现骨髓细胞减少和严重附着点炎的放射学证据.免疫分析显示患者的外周血单核细胞中有突出的干扰素特征，对I型和II型干扰素的刺激也过敏。患者对托法替尼表现出良好的临床和功能实验室反应，一种破坏干扰素信号的Janus激酶抑制剂。我们的案例强调了需要利用多学科诊断方法，并考虑对非典型免疫介导的血小板减少症表型患者的先天性免疫错误进行全面的遗传评估。
