Immune Dysregulation Syndrome With De Novo CTLA4 Germline Mutation Responsive to Abatacept Therapy
Immune Dysregulation Syndrome With De Novo CTLA4 Germline Mutation Responsive to Abatacept Therapy
复制标题
免疫失调综合征与阿巴西普治疗有反应的 CTLA4 种系从头突变
DOI：
10.1007/s12185-020-02834-9
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发表时间：
2020
影响因子：
2.1
通讯作者：
Kimura S
中科院分区：
文献类型：
--
作者：
Ureshino H;Koarada S;Kamachi K;Yoshimura M;Yokoo M;Kubota Y;Ando T;Ichinohe T;Morio T;Kimura S
调节性T细胞(Tregs)通过细胞毒性T淋巴细胞抗原4(CTLA4)信号通路，是哺乳动物自我耐受的主要介质。最近报道了一种与CTLA4基因杂合胚系突变相关的免疫调节失调综合征。临床特征包括反复感染、全身性淋巴结病、各种自身免疫状况、低丙种球蛋白血症和常染色体显性遗传，这是原发免疫缺陷病(PID)的特征。PID的症状是不同的，很少有零星的新CTLA4胚系突变的患者被描述。在这里，我们报告了一例26岁的男性患者，患有免疫调节失调综合征和新的CTLA4胚系突变。患者表现出几个与盆腔炎相关的临床特征。下一代测序发现，CTLA4基因外显子2有一个CTLA4胚系突变，c.436G>；A；p.G146R。桑格测序证实，这名患者是他家庭中唯一携带这种胚系突变的成员。患者被诊断为与新生生殖细胞CTLA4突变相关的免疫调节失调综合征，并伴有类固醇难治性类风湿性关节炎。阿巴塔塞普是一种CTLA4-免疫球蛋白融合分子，开始治疗，患者的临床症状显著缓解。由于伴有CTLA4胚系突变的PID很少见，患者可能被漏诊，医生应了解PID的特点。
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 inCTLA4was 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 novoCTLA4germline mutations have been described. Here, we report the case of a 26-year-old man with an immune dysregulation syndrome and a de novoCTLA4germline mutation. The patient exhibited several clinical features associated with PID. Next-generation sequencing revealed aCTLA4germline mutation, c.436G>A; p.G146R, in exon 2 ofCTLA4. 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 germlineCTLA4mutation, 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 withCTLA4germline mutation is rare and patients may be under-diagnosed, physicians should be aware of the features of PID.