An efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease.
An efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease.
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DOI：
10.1038/s41467-022-28353-1
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发表时间：
2022-02-16
影响因子：
16.6
通讯作者：
Elias JE
中科院分区：
文献类型：
--
作者：
Palanski BA;Weng N;Zhang L;Hilmer AJ;Fall LA;Swaminathan K;Jabri B;Sousa C;Fernandez-Becker NQ;Khosla C;Elias JE
乳糜泻（CeD）是一种自身免疫性疾病，由食用小麦、大麦和黑麦中的谷蛋白引起。麸质抵抗胃肠道蛋白水解，产生引起CeD患者炎症的肽。尽管谷蛋白和CeD之间的联系已经确立，但从未以公正的方式从人类中鉴定出由膳食蛋白质产生的化学定义的生物可利用肽。这在很大程度上归因于技术挑战，阻碍了我们对遇到免疫系统的潜在不同肽种类的了解。在这里，我们开发了一种液相色谱-质谱工作流程，用于尿肽组的非靶向序列分析。我们检测到超过600种不同的饮食肽，其中约35%具有CeD相关的T细胞表位，约5%已知刺激先天免疫应答。值得注意的是，来自CeD患者的谷蛋白肽在定性和定量上与对照不同。我们的结果为了解麸质免疫原性、改善CeD管理以及表征膳食和尿液肽组提供了新的基础。来自小麦的谷蛋白肽进入血液并通过尿液排出，但尚未进行化学表征。在这里，作者通过质谱法表明，可以在健康人和乳糜泻患者之间检测到尿肽的定量和定性差异。
Celiac disease (CeD) is an autoimmune disorder induced by consuming gluten proteins from wheat, barley, and rye. Glutens resist gastrointestinal proteolysis, resulting in peptides that elicit inflammation in patients with CeD. Despite well-established connections between glutens and CeD, chemically defined, bioavailable peptides produced from dietary proteins have never been identified from humans in an unbiased manner. This is largely attributable to technical challenges, impeding our knowledge of potentially diverse peptide species that encounter the immune system. Here, we develop a liquid chromatographic-mass spectrometric workflow for untargeted sequence analysis of the urinary peptidome. We detect over 600 distinct dietary peptides, of which ~35% have a CeD-relevant T cell epitope and ~5% are known to stimulate innate immune responses. Remarkably, gluten peptides from patients with CeD qualitatively and quantitatively differ from controls. Our results provide a new foundation for understanding gluten immunogenicity, improving CeD management, and characterizing the dietary and urinary peptidomes. Gluten peptides from wheat enter the bloodstream and are excreted in urine but are yet to be chemically characterised. Here, the authors show by mass spectrometry that quantitative and qualitative differences in urinary peptides can be detected between healthy people and patients with celiac disease.
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DOI：
10.1109/tvcg.2014.2346248
发表时间：
2014-12
影响因子：
5.2
作者：
Lex A;Gehlenborg N;Strobelt H;Vuillemot R;Pfister H
通讯作者：
Pfister H
影响因子：
15.3
作者：
Arentz-Hansen, H;Korner, R;Molberg, O;Quarsten, H;Vader, W;Kooy, Y M;Lundin, K E;Koning, F;Roepstorff, P;Sollid, L M;McAdam, S N
通讯作者：
McAdam, S N
影响因子：
24.5
作者：
Moreno ML;Cebolla Á;Muñoz-Suano A;Carrillo-Carrion C;Comino I;Pizarro Á;León F;Rodríguez-Herrera A;Sousa C
通讯作者：
Sousa C
影响因子：
6.1
作者：
Diaz-Amigo, Carmen;Popping, Bert
通讯作者：
Popping, Bert
影响因子：
29.4
作者：
Hoydahl, Lene Stokken;Richter, Lisa;Loset, Geir Age
通讯作者：
Loset, Geir Age