Atypical Hemolytic Uremic Syndrome Associated With Complement Factor H Autoantibodies and CFHR1/CFHR3 Deficiency
Atypical Hemolytic Uremic Syndrome Associated With Complement Factor H Autoantibodies and CFHR1/CFHR3 Deficiency
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DOI：
10.1203/pdr.0b013e3181b1bd4a
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发表时间：
2009-09-01
影响因子：
3.6
通讯作者：
Cheong, Hae Il
中科院分区：
文献类型：
--
作者：
Lee, Beom Hee;Kwak, Soo Heon;Cheong, Hae Il
虽然补体因子H （CFH）的遗传缺陷是非典型溶血性尿毒症综合征（aHUS）的常见原因，但CFH自身抗体（CFH- ab）的发展也被认为是aHUS的获得性原因。最近，CFH-Ab的发展与cfh相关蛋白CFHR1和CFHR3的缺乏之间存在相关性。本研究对3例确诊为aHUS且CFH- ab阳性的女性患者进行了血浆补体谱测定，并对CFH、CFI、MCP、CFHR1和CFHR3基因进行了遗传分析。3例患者急性期血浆均显示C3低、CFH抗原水平低或低于正常水平，CFH- ab滴度高。所有患者还表现出血浆CFHR1完全缺失和CFHR1/CFHR3纯合基因组缺失，但没有CFH、CFI或MCP突变。所有患者均接受血浆置换治疗，其中2例患者需要额外的免疫抑制治疗。这些患者有一种新的aHUS亚组，其特征是遗传（CFHR1/CFHR3的纯合缺失）和获得性（CFH-Ab的发展）因子的组合。患者可能需要强化免疫抑制治疗，除了血浆置换。筛查CFH-Ab和CFHR1/CFHR3缺乏症应包括在aHUS患者的诊断测试中。（儿科研究66:336- 340,2009）
Although genetic defect of complement factor H (CFH) is a common cause of atypical hemolytic uremic syndrome (aHUS), development of autoantibodies to CFH (CFH-Ab) is also known to be an acquired cause of aHUS. Recently, a correlation between the development of CFH-Ab and the deficiency of the CFH-related proteins, CFHR1 and CFHR3, was identified. In this study, plasma complement profiles were measured and genetic analysis of the CFH, CFI, MCP, CFHR1, and CFHR3 genes were performed in three female patients diagnosed with aHUS with positive CFH-Ab. Acute stage plasmas of all the three patients revealed low C3, low or low-normal CFH antigenic levels, and high titers of CFH-Ab. All the patients also showed complete plasma CFHR1 deficiency and homozygous genomic deletion of CFHR1/CFHR3, but none had CFH, CFI, or MCP mutations. All the patients were treated with plasmapheresis, and two patients required additional immunosuppressive therapy. These patients had a novel subgroup of aHUS characterized by a combination of genetic (a homozygous deletion of CFHR1/CFHR3) and acquired (development of CFH-Ab) factors. Patients with this disease may need intensive immunosuppressive therapy in addition to plasmapheresis. Screening for CFH-Ab and the CFHR1/CFHR3 deficiency should be included in the diagnostic tests for patients with aHUS. (Pediatr Res 66: 336-340, 2009)