Regulatory T-cells (Tregs) are major mediators of mammalian self-tolerance via cytotoxic T-lymphocyte antigen 4 (CTLA4) signaling pathways. An immune dysregulation syndrome associated with heterozygous germline mutations in CTLA4 was recently reported. Clinical features include recurrent infections, systemic lymphadenopathy, various autoimmune conditions, hypogammaglobulinemia, and autosomal dominant inheritance, characteristic of primary immunodeficient disease (PID). PID symptoms are variable and few patients with sporadic de novo CTLA4 germline mutations have been described. Here, we report the case of a 26-year-old man with an immune dysregulation syndrome and a de novo CTLA4 germline mutation. The patient exhibited several clinical features associated with PID. Next-generation sequencing revealed a CTLA4 germline mutation, c.436G>A; p.G146R, in exon 2 of CTLA4. Sanger sequencing confirmed the patient was the only member of his family with this germline mutation. The patient was diagnosed with an immune dysregulation syndrome associated with de novo germline CTLA4 mutation, complicated by steroid-refractory rheumatoid arthritis. Treatment with abatacept, a CTLA4-immunoglobulin fusion molecule, was initiated, resulting in dramatic resolution of the patient's clinical symptoms. As PID with CTLA4 germline mutation is rare and patients may be under-diagnosed, physicians should be aware of the features of PID.

中文翻译：

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免疫失调综合征，伴有对abatacept治疗有反应的从头CTLA4种系突变。

调节性T细胞（Tregs）是哺乳动物通过细胞毒性T淋巴细胞抗原4（CTLA4）信号通路自我耐受的主要介质。最近报道了与CTLA4杂合子系突变相关的免疫失调综合症。临床特征包括反复感染，全身淋巴结肿大，各种自身免疫性疾病，低血球蛋白血症和常染色体显性遗传，这是原发性免疫缺陷疾病（PID）的特征。PID症状多变，很少有散发性从头CTLA4种系突变患者。在这里，我们报告了一个26岁的男人，患有免疫失调综合症和从头CTLA4种系突变的病例。该患者表现出与PID相关的几种临床特征。下一代测序揭示了CTLA4种系突变，c.436G> A。p。G146R，在CTLA4的第2外显子中。Sanger测序证实该患者是该种系突变的唯一家庭成员。该患者被诊断患有与新生殖系CTLA4突变相关的免疫失调综合症，并伴有类固醇难治性类风湿关节炎。开始使用abatacept（一种CTLA4免疫球蛋白融合分子）进行治疗，从而显着缓解了患者的临床症状。由于伴有CTLA4种系突变的PID很少见，患者可能未得到充分诊断，因此医生应了解PID的特征。并发类固醇难治性类风湿关节炎。开始使用abatacept（一种CTLA4免疫球蛋白融合分子）进行治疗，从而显着缓解了患者的临床症状。由于伴有CTLA4种系突变的PID很少见，患者可能未得到充分诊断，因此医生应了解PID的特征。并发类固醇难治性类风湿关节炎。开始使用abatacept（一种CTLA4免疫球蛋白融合分子）进行治疗，从而显着缓解了患者的临床症状。由于伴有CTLA4种系突变的PID很少见，患者可能未得到充分诊断，因此医师应注意PID的特征。