Ectodysplasin A in Biological Fluids and Diagnosis of Ectodermal Dysplasia
Ectodysplasin A in Biological Fluids and Diagnosis of Ectodermal Dysplasia
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DOI：
10.1177/0022034516673562
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发表时间：
2017-02-01
影响因子：
7.6
通讯作者：
Schneider, P.
中科院分区：
文献类型：
--
作者：
Podzus, J.;Kowalczyk-Quintas, C.;Schneider, P.
肿瘤坏死因子家族配体胞外营养不良蛋白A(EDA)由两个全长剪接变异体EDA1和EDA2组成，分别与EDA受体(EDAR)和X-连锁EDA受体(XEDAR/EDA2R)结合。EDA或EDAR的失活突变会导致少汗性外胚层发育不良(HED)，这是一种以牙齿、头发和腺体畸形为特征的疾病，较轻微的缺陷只影响牙齿。EDA早在胚胎胎盘阶段就在外胚层附件的发育过程中起作用，并在成体附件功能中发挥作用。在这项研究中，作者测量了血清、唾液和干血斑点中的EDA。作者检测到脐带血中循环EDA水平比成人血清中高3到4倍。EDA以受体结合活性形式EDA1为主，胎牛血清中也有少量EDA2。EDA缺陷者的血清中要么含有背景EDA水平，要么含有不能与重组EDAR结合的低水平EDA。一名EDA V262F错义突变患者的血清中含有能够与EDAR结合的低水平EDA，这种突变导致了一种较轻的X连锁HED(XLHED)。在两名轻度感染的携带者中，检测到中等水平的EDA，而在一名严重感染的携带者中，血清中没有活跃的EDA。在正常成人的唾液中也检测到少量的EDA。最后，EDA可以在干燥在滤纸上的野生型成人血或脐带血中测得，其水平明显高于EDA缺乏的血液中的测定值。EDA水平的测量结合受体结合分析可能有助于诊断全部或部分EDA缺乏症。
The tumor necrosis factor (TNF) family ligand ectodysplasin A (EDA) is produced as 2 full-length splice variants, EDA1 and EDA2, that bind to EDA receptor (EDAR) and X-linked EDA receptor (XEDAR/EDA2R), respectively. Inactivating mutations in Eda or Edar cause hypohidrotic ectodermal dysplasia (HED), a condition characterized by malformations of the teeth, hair and glands, with milder deficiencies affecting only the teeth. EDA acts early during the development of ectodermal appendagesas early as the embryonic placode stageand plays a role in adult appendage function. In this study, the authors measured EDA in serum, saliva and dried blood spots. The authors detected 3- to 4-fold higher levels of circulating EDA in cord blood than in adult sera. A receptor binding-competent form of EDA1 was the main form of EDA but a minor fraction of EDA2 was also found in fetal bovine serum. Sera of EDA-deficient patients contained either background EDA levels or low levels of EDA that could not bind to recombinant EDAR. The serum of a patient with a V262F missense mutation in Eda, which caused a milder form of X-linked HED (XLHED), contained low levels of EDA capable of binding to EDAR. In 2 mildly affected carriers, intermediate levels of EDA were detected, whereas a severely affected carrier had no active EDA in the serum. Small amounts of EDA were also detectable in normal adult saliva. Finally, EDA could be measured in spots of wild-type adult or cord blood dried onto filter paper at levels significantly higher than that measured in EDA-deficient blood. Measurement of EDA levels combined with receptor-binding assays might be of relevance to aid in the diagnosis of total or partial EDA deficiencies.