Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease.
Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease.
复制标题
ATP 7B肽的直接测量在Wilson病的诊断中是高度有效的。
DOI：
10.1053/j.gastro.2021.02.052
复制
发表时间：
2021-06
期刊：
影响因子：
29.4
通讯作者：
Hahn SH
中科院分区：
文献类型：
--
作者：
Collins CJ;Yi F;Dayuha R;Duong P;Horslen S;Camarata M;Coskun AK;Houwen RHJ;Pop TL;Zoller H;Yoo HW;Jung SW;Weiss KH;Schilsky ML;Ferenci P;Hahn SH
现有的临床标准和基因检测对肝豆状核变性(WD)的诊断都有很大的局限性，经常造成患者识别的模糊性，导致延迟诊断和无效的处理。通过直接测量患者干血斑(DBS)样本中的替代多肽来指示ATP7B蛋白浓度，可以提供WD的主要证据。对来自不同背景的患者样本进行ATP7B浓度测量，确定诊断潜力，并将结果与个别患者的生化和遗传学结果进行比较。获得IRB批准后，从三个国际和两个国内学术中心的生物信息库获得264份样品，并获得150份正常对照。研究对象包括基因或临床确诊的WD患者，其莱比锡评分大于3，且患者家族成员携带有专性杂合子(携带者)。用免疫亲和富集质谱法测定ATP7B多肽。用两个ATP7B多肽测定ATP7B蛋白浓度。ROC曲线分析得出AUC为0.98。ATP7B 887序列分析的敏感性为91.2%，特异性为98.1%，阳性预测值为98.0%，阴性预测值为91.5%。在铜蓝蛋白浓度正常(>；20 mg/dL)的患者中，14/16(87.5%)存在ATP7B缺陷。在没有明确遗传结果的患者中，94%是ATP7B缺陷。ATP7B多肽的定量在92.1%的病例中有效地识别了WD患者，并减少了CP和遗传分析导致的歧义。基因结果不明确的患者可以得到明确的诊断，这对非侵入性诊断有很大帮助。建议的结合ATP7B肽浓度的诊断评分和算法可以快速诊断并补充目前的莱比锡评分系统。建议的诊断评分和算法结合DBS中ATP7B肽浓度可以快速诊断并补充目前的莱比锡评分系统。
Both existing clinical criteria and genetic testing have significant limitations for the diagnosis of Wilson’s Disease (WD) often creating ambiguities in patient identification leading to delayed diagnosis and ineffective management. ATP7B protein concentration, indicated by direct measurement of surrogate peptides from patient dried blood spot (DBS) samples, could provide primary evidence of WD. ATP7B concentrations were measured in patient samples from diverse backgrounds, diagnostic potential is determined, and results are compared to biochemical and genetic results from individual patients. 264 samples from biorepositories at three international and two domestic academic centers and 150 normal controls were obtained after IRB approval. Genetically or clinically confirmed WD patients with a Leipzig score over 3 and obligate heterozygote (carriers) from affected family members were included. ATP7B peptide measurements were made by immunoaffinity enrichment mass spectrometry. Two ATP7B peptides were used to measure ATP7B protein concentration. ROC curve analysis generates an AUC of 0.98. ATP7B peptide analysis of the sequence ATP7B 887 was found to have a sensitivity of 91.2%, specificity of 98.1%, positive predictive value (PPV) of 98.0%, and a negative predictive (NPV) value of 91.5%. In patients with normal ceruloplasmin concentrations (> 20 mg/dL), 14/16 (87.5%) were ATP7B deficient. In patients without clear genetic results, 94% were ATP7B deficient. Quantification of ATP7B peptide effectively identified WD patients in 92.1% of presented cases and reduced ambiguities resulting from Cp and genetic analysis. Clarity is brought to patients with ambiguous genetic results, significantly aiding in non-invasive diagnosis. A proposed diagnostic score and algorithm incorporating ATP7B peptide concentrations can be rapidly diagnostic and supplemental to current Leipzig scoring systems. A proposed diagnostic score and algorithm incorporating ATP7B peptide concentrations in DBS can be rapidly diagnostic and supplemental to current Leipzig scoring systems.
登录
查看更多内容
影响因子：
30.8
作者：
BULL, PC;THOMAS, GR;COX, DW
通讯作者：
COX, DW
DOI：
10.1111/nyas.12423
发表时间：
2014-01-01
期刊：
HUMAN DISORDERS OF COPPER METABOLISM II
影响因子：
--
作者：
Hahn, Si Houn
通讯作者：
Hahn, Si Houn
影响因子：
29.4
作者：
Huster D;Kühne A;Bhattacharjee A;Raines L;Jantsch V;Noe J;Schirrmeister W;Sommerer I;Sabri O;Berr F;Mössner J;Stieger B;Caca K;Lutsenko S
通讯作者：
Lutsenko S
影响因子：
4.4
作者：
Anderson, NL;Anderson, NG;Pearson, TW
通讯作者：
Pearson, TW
影响因子：
7.3
作者：
Collins, Christopher J.;Chang, Irene J.;Hahn, Si Houn
通讯作者：
Hahn, Si Houn