Salivary proline-rich proteins and gluten: Do structural similarities suggest a role in celiac disease?
Salivary proline-rich proteins and gluten: Do structural similarities suggest a role in celiac disease?
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DOI：
10.1002/prca.201400170
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发表时间：
2015-10
期刊：
影响因子：
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通讯作者：
Helmerhorst EJ
中科院分区：
文献类型：
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作者：
Tian N;Messana I;Leffler DA;Kelly CP;Hansen J;Cabras T;D'Alessandro A;Schuppan D;Castagnola M;Helmerhorst EJ
麸质蛋白是乳糜泻（CD）的罪魁祸首，其一级结构与人类唾液富含脯氨酸蛋白（PRPs）有惊人的相似性。两者都富含脯氨酸和谷氨酰胺残基，这些残基通常在其序列中连续出现。我们调查了健康和CD患者唾液PRPs谱的潜在差异。从CD患者、难治性CD患者、有胃肠道不适但无CD的患者和健康对照组收集刺激唾液分泌物。通过阴离子和SDS-PAGE、PCR和LC-ESI-MS表征PRP亚型/肽。酸性PRP亚型PIF、Db、Pa、PRP 1和PRP 2的基因频率在组间无差异。在蛋白质水平上，PRPs肽显示出微小的组差异，但这些无法区分CD和/或难治性CD组与对照组。这项广泛的研究确定，唾液PRP，尽管相似的面筋蛋白，没有表现出明显的相关性与CD，因此不会作为诊断标志物的疾病。对CD中的谷蛋白样PRP蛋白的耐受性的结构基础值得进一步探索，并且可能导致开发可用于治疗的缺乏免疫原性的谷蛋白样类似物。
Gluten proteins, the culprits in celiac disease (CD), show striking similarities in primary structure with human salivary proline-rich proteins (PRPs). Both are enriched in pro-line and glutamine residues that often occur consecutively in their sequences. We investigated potential differences in the spectrum of salivary PRPs in health and CD. Stimulated salivary secretions were collected from CD patients, patients with refractory CD, patients with gastrointestinal complaints but no CD, and healthy controls. PRP isoforms/peptides were characterized by anionic and SDS-PAGE, PCR, and LC-ESI-MS. The gene frequencies of the acidic PRP isoforms PIF, Db, Pa, PRP1, and PRP2 did not differ between groups. At the protein level, PRPs peptides showed minor group differences, but these could not differentiate the CD and/or refractory CDs groups from the controls. This extensive study established that salivary PRPs, despite similarity to gluten proteins, show no apparent correlation with CD and thus will not serve as diagnostic markers for the disease. The structural basis for the tolerance to the gluten-like PRP proteins in CD is worthy of further exploration and may lead to the development of gluten-like analogs lacking immunogenicity that could be used therapeutically.