Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease.
Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease.
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尽管与麸质具有序列同源性，但唾液中富含脯氨酸的蛋白质不会引发乳糜泻发病机制中的核心免疫反应。
DOI：
10.1152/ajpgi.00157.2015
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Helmerhorst,EvaJ
中科院分区：
文献类型：
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作者：
Tian,Na;Leffler,DanielA;Kelly,CiaranP;Hansen,Joshua;Marietta,EricV;Murray,JosephA;Schuppan,Detlef;Helmerhorst,EvaJ
乳糜泻（CD）是一种由摄入麸质引发的炎症性疾病，导致免疫介导的小肠粘膜损伤。谷蛋白在氨基酸组成和序列上与人唾液中的富含脯氨酸的蛋白（PRP）惊人地相似。基于这一特征及其在胃肠道中的共同目的地，我们假设唾液PRPs可能调节CD中谷蛋白介导的免疫应答。腮腺唾液分泌物收集CD患者，难治性CD患者，非CD患者功能性胃肠道投诉，和健康对照。用抗麦醇溶蛋白抗体探测PRP与谷蛋白的结构相似性。在CD患者来源的外周血单核细胞和CD的人源化转基因HLA-DQ 2/DQ 8小鼠模型中研究了对PRP的免疫应答。抗麦醇溶蛋白抗体弱交叉反应，丰富的唾液淀粉酶，但不与PRP。同样，识别潜在抗原性谷蛋白表位的R5抗体对所有组的唾液蛋白显示出可忽略的反应性。在外周血单核细胞的炎症反应引起的麦胶蛋白，而对PRP的反应是类似的控制水平，和PRP没有竞争与麦胶蛋白的免疫刺激。在体内，PRP肽在转基因HLA-DQ 2/DQ 8小鼠模型中耐受良好且无免疫原性。总的来说，虽然结构上类似于饮食麸质，唾液PRP在CD患者和CD的转基因HLA-DQ 2/DQ 8小鼠模型中是非免疫原性的。这是可能的，唾液PRPs在耐受诱导面筋在生命早期发挥作用。破译唾液PRPs缺乏免疫原性的结构基础可能会进一步加深我们对麸质毒性的理解。
Celiac disease (CD) is an inflammatory disorder triggered by ingested gluten, causing immune-mediated damage to the small-intestinal mucosa. Gluten proteins are strikingly similar in amino acid composition and sequence to proline-rich proteins (PRPs) in human saliva. On the basis of this feature and their shared destination in the gastrointestinal tract, we hypothesized that salivary PRPs may modulate gluten-mediated immune responses in CD. Parotid salivary secretions were collected from CD patients, refractory CD patients, non-CD patients with functional gastrointestinal complaints, and healthy controls. Structural similarities of PRPs with gluten were probed with anti-gliadin antibodies. Immune responses to PRPs were investigated toward CD patient-derived peripheral blood mononuclear cells and in a humanized transgenic HLA-DQ2/DQ8 mouse model for CD. Anti-gliadin antibodies weakly cross-reacted with the abundant salivary amylase but not with PRPs. Likewise, the R5 antibody, recognizing potential antigenic gluten epitopes, showed negligible reactivity to salivary proteins from all groups. Inflammatory responses in peripheral blood mononuclear cells were provoked by gliadins whereas responses to PRPs were similar to control levels, and PRPs did not compete with gliadins in immune stimulation. In vivo, PRP peptides were well tolerated and nonimmunogenic in the transgenic HLA-DQ2/DQ8 mouse model. Collectively, although structurally similar to dietary gluten, salivary PRPs were nonimmunogenic in CD patients and in a transgenic HLA-DQ2/DQ8 mouse model for CD. It is possible that salivary PRPs play a role in tolerance induction to gluten early in life. Deciphering the structural basis for the lack of immunogenicity of salivary PRPs may further our understanding of the toxicity of gluten.