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乳糜泻、自身免疫性糖尿病和2型糖尿病患者肠上皮细胞损伤及凋亡的血清学标志物

Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2.

作者信息

Hoffmanová I, Sánchez D, Hábová V, Anděl M, Tučková L, Tlaskalová-Hogenová H

机构信息

Second Department of Internal Medicine, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, Department of Immunology, Institute of Microbiology, v.v.i., Czech Academy of Sciences, Prague, Czech Republic.

出版信息

Physiol Res. 2015;64(4):537-46. doi: 10.33549/physiolres.932916. Epub 2014 Dec 3.

Abstract

Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis - cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage - intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (P<0.001), I-FABP (P<0.01) and sCD14 (P<0.05) in CLD when compared to healthy controls. However, the levels of cCK-18 (P<0.01) and I-FABP (P<0.01) in CLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (P<0.001), and T1D/INS (P<0.01, P<0.001). Twenty-two out of 43 CLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes.

摘要

小肠黏膜屏障完整性受损可能是免疫介导的胃肠道疾病的病因。我们检测了未经治疗的乳糜泻(CLD)患者、采用无麸质饮食的患者(CLD-GFD)、自身免疫性糖尿病(T1D)患者、伴有胰岛炎的T1D患者(T1D/INS)以及2型糖尿病(T2D)患者血清中的上皮细胞凋亡标志物——细胞角蛋白18半胱天冬酶切割片段(cCK-18),以及肠细胞损伤标志物——肠脂肪酸结合蛋白(I-FABP)和可溶性CD14(sCD14)。我们发现,与健康对照相比,CLD患者的cCK-18(P<0.001)、I-FABP(P<0.01)和sCD14(P<0.05)水平升高。然而,与对照相比,CLD-GFD患者的cCK-18(P<0.01)和I-FABP(P<0.01)水平更高。有趣的是,在T2D和T1D患者中发现cCK-18和I-FABP水平升高(P<0.001),在T1D/INS患者中也是如此(P<0.01,P<0.001)。43例CLD患者中有22例cCK-18血清阳性,19/43例I-FABP血清阳性,11/43例sCD14血清阳性;30例T2D患者中有9例cCK-18阳性,20例T1D/INS患者中有5例sCD14阳性,而在对照组中,只有3/41例cCK-18阳性,3/41例I-FABP阳性,1/41例sCD14阳性。我们首次记录了CLD患者sCD14血清阳性,以及血清cCK-18和I-FABP作为CLD、CLD-GFD和糖尿病肠道损伤标志物的潜在用途。

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