Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.
Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Clin Immunol. 2023 Feb;247:109214. doi: 10.1016/j.clim.2022.109214. Epub 2023 Jan 4.
Glycoprotein 2 (GP2) is an autoantigen in Crohn's (CD) and coeliac disease (CeD). We assessed GP2-isoform (GP2)-expression in intestinal biopsies of paediatric patients with CD, CeD, ulcerative colitis (UC), and healthy children (HC). Transcription of GP2 was elevated in proximal small intestine in CeD and CD patients (only GP2) compared to jejunum (CeD/CD) and large bowel (CD). CeD patients demonstrated higher duodenal GP2-mRNA levels compared to HC/UC patients whereas CD patients showed higher GP2-mRNA levels compared to UC patients. Duodenal synthesis of only small GP2 isoforms (GP2) was demonstrated in epithelial cells in patients/HC and in Brunner glands (also large isoforms) with a more frequent apical location in CD/CeD patients. All four GP2 isoforms interacted with gliadin and phosphopeptidomannan. Gliadin digestion improved binding to GP2 isoforms. GP2 binding to CeD/CD-related antigens, elevated duodenal GP2-mRNA transcription, and GP2-protein secretion in Brunner glands of CeD/CD patients suggest an autoimmune CeD/CD link.
糖蛋白 2（GP2）是克罗恩病（CD）和乳糜泻（CeD）的自身抗原。我们评估了儿科 CD、CeD、溃疡性结肠炎（UC）和健康儿童（HC）患者的肠活检组织中 GP2 异构体（GP2）的表达。与空肠（CeD/CD）和大肠（CD）相比，CeD 和 CD 患者的近端小肠中 GP2 的转录水平升高（仅 GP2）。与 HC/UC 患者相比，CeD 患者的十二指肠 GP2-mRNA 水平更高，而与 UC 患者相比，CD 患者的 GP2-mRNA 水平更高。在患者/HC 的上皮细胞和 Brunner 腺（也有大的异构体）中，仅检测到小的 GP2 异构体（GP2）的十二指肠合成，并且在 CD/CeD 患者中更频繁地位于顶端位置。所有四种 GP2 异构体均与麦胶蛋白和磷酸肽聚糖相互作用。麦胶蛋白消化可增强与 GP2 异构体的结合。GP2 与 CeD/CD 相关抗原的结合、十二指肠 GP2-mRNA 转录的升高以及 CeD/CD 患者 Brunner 腺中 GP2 蛋白的分泌提示存在自身免疫性 CeD/CD 联系。
