Primary glomerulonephritis with isolated C3 deposits:: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome
Primary glomerulonephritis with isolated C3 deposits:: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome
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DOI：
10.1136/jmg.2006.045328
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发表时间：
2007-03-01
影响因子：
4
通讯作者：
Fakhouri, Fadi
中科院分区：
文献类型：
--
作者：
Servais, Aude;Fremeaux-Bacchi, Veronique;Fakhouri, Fadi
简介：补体旁路途径（CAP）的异常控制（因子H、因子I和膜辅因子蛋白（MCP）缺乏）是发生溶血性尿毒综合征（HUS）的公认危险因素。在某些情况下，溶血尿毒综合征可能与一种罕见的肾小球肾炎与孤立的C3存款（肾小球肾炎C3）。我们确定是否HUS和肾小球肾炎C3共享共同的遗传易感factors.Methods：我们确定了19例肾小球肾炎C3。我们测量了循环补体成分的水平，进行检测C3肾炎因子（C3 NeF）和筛选因子H，因子I和MCP编码基因的突变的存在下进行分析。I组（n = 13）为典型的I型膜增生性肾小球肾炎（肾小球肾炎C3伴膜增生性肾小球肾炎（MPGN））和组II（n = 6）的特征在于在不存在系膜增生的情况下的系膜和膜上C3沉积（肾小球肾炎C3不伴MPGN）。在6例无MPGN的C3肾小球肾炎患者中有4例检测到补体调节基因突变（2例H因子基因杂合突变，1例H因子抗原水平低，因子I基因杂合突变（2例患者）），仅2/13例肾小球肾炎C3伴MPGN患者（因子H基因杂合突变（1例）和CD 46基因双杂合突变（1例））。相反，C3 NeF存在于5/13例肾小球肾炎C3与MPGN和2/6例肾小球肾炎C3无MPGN，其中一人有一个H因子突变。结论：HUS和肾小球肾炎C3无MPGN共享共同的遗传危险因素。CAP的体质性或获得性失调可能与广泛的疾病有关，从HUS到肾小球肾炎C3伴MPGN。
Introduction: Abnormal control of the complement alternative pathway ( CAP) ( factor H, factor I and membrane cofactor protein (MCP) deficiencies) is a well established risk factor for the occurrence of haemolytic uraemic syndrome (HUS). In some instances, HUS may be associated with an unusual glomerulonephritis with isolated C3 deposits ( glomerulonephritis C3). We determined whether HUS and glomerulonephritis C3 share common genetic susceptibility factors.Methods: We identified 19 patients with glomerulonephritis C3. We measured levels of circulating complement components, performed assays for the detection of C3 nephritic factor (C3NeF) and screened factor H, factor I and MCP coding genes for the presence of mutations.Results: Patients were divided in two groups based on renal pathology findings: group I (n = 13) had typical features of type I membranoproliferative glomerulonephritis ( glomerulonephritis C3 with membranoproliferative glomerulonephritis ( MPGN)) and group II ( n = 6) was characterised by mesangial and epimembranous C3 deposits in the absence of mesangial proliferation ( glomerulonephritis C3 without MPGN). Mutations in complement regulatory genes were detected in 4/6 patients with glomerulonephritis C3 without MPGN ( heterozygous mutations in factor H gene (two patients) with low factor H antigenic level in one case, heterozygous mutations in factor I gene ( two patients)) and in only 2/13 patients with glomerulonephritis C3 with MPGN ( heterozygous mutations in factor H gene ( one patient) and double heterozygous mutation in CD 46 gene (one patient)). In contrast, C3NeF was present in 5/13 patients with glomerulonephritis C3 with MPGN and in 2/6 patients with glomerulonephritis C3 without MPGN, one of whom had a factor H mutation.Conclusion: HUS and glomerulonephritis C3 without MPGN share common genetic risk factors. Constitutional or acquired dysregulation of the CAP is probably associated with a wide spectrum of diseases, ranging from HUS to glomerulonephritis C3 with MPGN.