Dense deposit disease associated with monoclonal gammopathy of undetermined significance.
Dense deposit disease associated with monoclonal gammopathy of undetermined significance.
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DOI：
10.1053/j.ajkd.2010.06.021
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Smith RJ
中科院分区：
文献类型：
--
作者：
Sethi S;Sukov WR;Zhang Y;Fervenza FC;Lager DJ;Miller DV;Cornell LD;Krishnan SG;Smith RJ
致密存款病（DDD）是一种罕见的肾小球疾病，通常影响儿童和年轻人，更不常见的老年患者。DDD的病理生理学基础是补体级联的旁路途径（AP）的不受控制的激活，最常见的是继发于C3转化酶（称为C3肾炎因子）的自身抗体，尽管因子H和该蛋白的自身抗体的突变可能会损害其功能，也会导致DDD。自1995年以来，我们在14例49岁或以上的患者中诊断出DDD;其中10例（71.4%）伴有意义不明的单克隆丙种球蛋白病（MGUS）。在本文所述的十个指标病例之一中，我们评估了AP，并证明了与补体活性一致的低血清AP蛋白水平、H因子H402等位基因的杂合性以及低水平的H因子自身抗体，这可能会影响H因子的能力调节AP活性。总的来说，这些发现表明，在一些MGUS成人中，DDD可能是由于对因子H（或其他补体蛋白）的自身抗体而发生的，这些抗体在允许的遗传背景下（因子H的H402等位基因）导致AP失调，随后发生肾小球损伤。因此，DDD在一些老年患者可能是一个独特的临床病理实体，代表了一种罕见的并发症MGUS。
Dense deposit disease (DDD) is a rare glomerular disease that typically affects children and young adults and much less commonly older patients. The pathophysiology underlying DDD is uncontrolled activation of the alternative pathway (AP) of complement cascade most frequently secondary to an autoantibody to C3 convertase called C3 nephritic factor, although mutations in factor H and auto-antibodies to this protein can impair its function and also cause DDD. Since 1995, we have diagnosed DDD in 14 patients 49 years of age or older; ten of these patients (71.4%) carry a concomitant diagnosis of monoclonal gammopathy of undetermined significance (MGUS). In one of ten, the index case described herein, we evaluated the AP and demonstrated low serum AP protein levels consistent with complement activity, heterozygosity for the H402 allele of factor H, and low levels of factor H autoantibodies, which can affect the ability of factor H to regulate AP activity. In aggregate, these findings suggest in some adults with MGUS, DDD may develop as a result of autoantibodies to factor H (or other complement proteins) that on a permissive genetic background (the H402 allele of factor H) lead to dysregulation of the AP with subsequent glomerular damage. Thus DDD in some older patients may be a distinct clinicopathologic entity that represents an uncommon complication of MGUS.
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影响因子：
3.6
作者：
Montes, Tamara;Goicoechea de Jorge, Elena;Rodriguez de Cordoba, Santiago
通讯作者：
Rodriguez de Cordoba, Santiago
DOI：
10.1073/pnas.0601094103
发表时间：
2006-06-20
影响因子：
11.1
作者：
Pickering, M. C.;Warren, J.;Botto, M.
通讯作者：
Botto, M.
影响因子：
13.6
作者：
Smith, Richard J. H.;Alexander, Jessy;Zipfel, Peter F.
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Zipfel, Peter F.
影响因子：
19.6
作者：
Sethi, Sanjeev;Gamez, Jeffrey D.;Vrana, Julie A.;Theis, Jason D.;Bergen, H. Robert, III;Zipfel, Peter F.;Dogan, Ahmet;Smith, Richard J. H.
通讯作者：
Smith, Richard J. H.
影响因子：
2.3
作者：
Lau, Keith K.;Smith, Richard J.;Butani, Lavjay
通讯作者：
Butani, Lavjay