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一种乳糜泻激活麦醇溶蛋白肽的无毒类似物:免疫调节的基础?

A non-toxic analogue of a coeliac-activating gliadin peptide: a basis for immunomodulation?

作者信息

Biagi F, Ellis H J, Parnell N D, Shidrawi R G, Thomas P D, O'Reilly N, Corazza G R, Ciclitira P J

机构信息

Gastroenterology Unit, GKT, St. Thomas' Hospital, London, UK.

出版信息

Aliment Pharmacol Ther. 1999 Jul;13(7):945-50. doi: 10.1046/j.1365-2036.1999.00512.x.

Abstract

BACKGROUND

A-gliadin residues 31-49 (peptide A) binds to HLA-DQ2 and is toxic to coeliac small bowel. Analogues of this peptide, which bind to DQ2 molecules but are non-toxic, may be a potential route to inducing tolerance to gliadin in patients with coeliac disease.

METHODS

Toxicity was investigated with small bowel organ culture in six patients with untreated coeliac disease, four with treated coeliac disease and six controls. Analogue peptides comprised alanine substituted variants of peptide A at L31 (peptide D), P36 (E), P38 (F), P39 (G) and P42 (H).

RESULTS

Peptides D and E were toxic in biopsies from some patients. Peptides F, G and H were not toxic.

CONCLUSIONS

Peptide F, which binds to DQ2 more strongly than peptide A, is not toxic in patients with coeliac disease in-vitro; this could be an initial step towards investigation of the induction of tolerance to gliadin in patients affected by coeliac disease.

摘要

背景

α-麦醇溶蛋白残基31 - 49(肽A)与HLA - DQ2结合,对乳糜泻患者的小肠有毒性。该肽的类似物虽能与DQ2分子结合但无毒,可能是诱导乳糜泻患者对麦醇溶蛋白产生耐受性的潜在途径。

方法

在6例未经治疗的乳糜泻患者、4例经治疗的乳糜泻患者和6例对照中,采用小肠器官培养研究毒性。类似物肽包括肽A在L31(肽D)、P36(E)、P38(F)、P39(G)和P42(H)处的丙氨酸取代变体。

结果

肽D和E在一些患者的活检组织中具有毒性。肽F、G和H无毒。

结论

肽F比肽A更强烈地结合DQ2,在体外对乳糜泻患者无毒;这可能是研究诱导乳糜泻患者对麦醇溶蛋白产生耐受性的第一步。

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