Proliferative Glomerulonephritis Secondary to Dysfunction of the Alternative Pathway of Complement
Proliferative Glomerulonephritis Secondary to Dysfunction of the Alternative Pathway of Complement
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DOI：
10.2215/cjn.07110810
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发表时间：
2011-05-01
影响因子：
9.8
通讯作者：
Smith, Richard. H.
中科院分区：
文献类型：
--
作者：
Sethi, Sanjeev;Fervenza, Fernando C.;Smith, Richard. H.
背景与目的致密存款病（dense deposit disease，DDD）是典型的膜增生性肾小球肾炎（membranoproliferative glomerulonephritis，MPGN），其补体旁路途径（alternative pathway，AP）的液相调节异常导致补体碎片在肾小球内积聚，常在缺乏免疫复合物的情况下产生MPGN损伤模式。最近描述的一种被称为具有C3沉积的GN（GN-C3）的实体与DDD具有许多相似之处。本研究的目的是评估AP功能的情况下，GN-C3。设计，设置，参与者，和测量五个最近的MPGN广泛C3沉积的情况下进行了研究。1例肾活检显示典型DDD表现。3例显示GN-C3，但无明显IG沉积;然而，不存在沿肾小球基底膜和系膜沿着的DDD致密沉积物的经典标志。结果所有病例均有AP激活的证据，包括可溶性膜攻击复合物水平升高（所有病例）、AP功能测定阳性（4例）和溶血测定阳性（1例）。发现自身抗体C3转化酶（2例）和因子H（1例）。因子H突变筛查确定了H402等位基因（所有病例）和c.C2867T p.T956M缺失突变（1例）。激光显微切割和质谱分析肾小球的GN-C3（两例）表现出非常相似的蛋白质组学轮廓DDD.Conclusions这些研究牵连AP失调罕见的肾脏疾病，包括GN-C3和DDD的频谱。Clin J Am Soc Nephrol 6：1009-1017，2011. doi：10.2215/CIN.07110810
Background and objectives dense deposit disease (DDD) is the prototypical membranoproliferative glomerulonephritis (MPGN), in which fluid-phase dysregulation of the alternative pathway (AP) of complement results in the accumulation of complement debris in the glomeruli, often producing an MPGN pattern of injury in the absence of immune complexes. A recently described entity referred to as GN with C3 deposition (GN-C3) bears many similarities to DDD. The purpose of this study was to evaluate AP function in cases of GN-C3.Design, setting, participants, & measurements Five recent cases of MPGN with extensive C3 deposition were studied. Renal biopsy in one case exhibited the classic findings of DDD. Three cases showed GN-C3 in the absence of significant Ig deposition; however, the classic hallmark of DDD dense deposits along the glomerular basement membranes and mesangium was absent. The remaining case exhibited features of both DDD and GN-C3.Results Evidence of AP activation was demonstrable in all cases and included increased levels of soluble membrane attack complex (all cases), positive AP functional assays (four cases), and a positive hemolytic assay (one case). Autoantibodies were found to C3 convertase (two cases) and to factor H (one case). Factor H mutation screening identified the H402 allele (all cases) and a c.C2867T p.T956M missence mutation (one case). Laser microdissection and mass spectrometry of glomeruli of GN-C3 (two cases) showed a proteomic profile very similar to DDD.Conclusions These studies implicate AP dysregulation in a spectrum of rare renal diseases that includes GN-C3 and DDD. Clin J Am Soc Nephrol 6: 1009-1017, 2011. doi: 10.2215/CIN.07110810