Sturgess R, Day P, Ellis H J, Lundin K E, Gjertsen H A, Kontakou M, Ciclitira P J
Rayne Institute Division of Pharmacology, St Thomas' Hospital, London, UK.
Lancet. 1994 Mar 26;343(8900):758-61. doi: 10.1016/s0140-6736(94)91837-6.
The exact nature of the cereal moiety that exacerbates coeliac disease is unknown. In-vitro studies have implicated both the N-terminal and far C-terminal domains of one of the wheat prolamins, A-gliadin. Peptides within these regions may act as epitopes that trigger immune events leading to enteropathy. We synthesized three peptides corresponding to amino-acids 3-21, 31-49, and 202-220 of A-gliadin. Four patients with coeliac disease were challenged by intraduodenal infusion of 1 g of gliadin or 200 mg of the synthetic peptides. Jejunal biopsies were taken before and at hourly intervals for 6 h after the infusion. Morphometric variables were measured and intraepithelial lymphocytes counted. Significant histological changes occurred in the small intestinal mucosa after challenge with a synthetic peptide corresponding to amino acids 31-49 of A-gliadin. The N-terminal peptide, residues 3-21 of A-gliadin, did not cause histological changes in any of the patients. In one of the four patients, minor histological changes following challenge with the peptide corresponding to residues 202-220 of A-gliadin were seen. Our results suggest that the oligopeptide corresponding to aminoacids 31-49 of A-gliadin is toxic in vivo, but there is no evidence of toxicity of the far N-terminal peptide, residues 3-21. The C-terminal peptide 202-220 may contain an epitope to which patients with coeliac disease display variable sensitivity. Since the oligopeptide corresponding to amino-acids 31-49 of A-gliadin is recognised by HLA DQ2-restricted T cells, the observed effects may be due to immune activation within the intestinal mucosa.
加剧乳糜泻的谷物部分的确切性质尚不清楚。体外研究表明，小麦醇溶蛋白之一的α-醇溶蛋白的N端和远C端结构域都与之有关。这些区域内的肽可能作为表位触发导致肠病的免疫反应。我们合成了对应于α-醇溶蛋白氨基酸3 - 21、31 - 49和202 - 220的三种肽。4名乳糜泻患者通过十二指肠内输注1 g醇溶蛋白或200 mg合成肽进行激发试验。在输注前以及输注后每小时进行一次空肠活检，持续6小时。测量形态学变量并计数上皮内淋巴细胞。用对应于α-醇溶蛋白氨基酸31 - 49的合成肽激发后，小肠黏膜出现了显著的组织学变化。α-醇溶蛋白N端肽（氨基酸3 - 21）在任何患者中均未引起组织学变化。在4名患者中的1名患者中，观察到用对应于α-醇溶蛋白氨基酸202 - 220的肽激发后有轻微的组织学变化。我们的结果表明，对应于α-醇溶蛋白氨基酸31 - 49的寡肽在体内具有毒性，但没有证据表明远N端肽（氨基酸3 - 21）有毒性。C端肽202 - 220可能包含一个表位，乳糜泻患者对其敏感性各不相同。由于对应于α-醇溶蛋白氨基酸31 - 49的寡肽可被HLA DQ2限制性T细胞识别，观察到的效应可能是由于肠黏膜内的免疫激活所致。
