Adriaanse Marlou P M, Leffler Daniel A, Kelly Ciaran P, Schuppan Detlef, Najarian Robert M, Goldsmith Jeffrey D, Buurman Wim A, Vreugdenhil Anita C E
Department of Pediatrics and Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University Medical Center, Maastricht, the Netherlands.
Department of Gastroenterology, Celiac Disease Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Am J Gastroenterol. 2016 Jul;111(7):1014-22. doi: 10.1038/ajg.2016.162. Epub 2016 May 17.
Response to gluten challenge (GC) is a key feature in diagnostic algorithms and research trials in celiac disease (CD). Currently, autoantibody titers, late responders to GC, and invasive duodenal biopsies are used to evaluate gluten responsiveness. This study investigated the accuracy of serum intestinal-fatty acid binding protein (I-FABP), a marker for intestinal epithelial damage, to predict intestinal damage during GC in patients with CD.
Twenty adult CD patients in remission underwent a two-week GC with 3 or 7.5 g of gluten daily. Study visits occurred at day -14, 0, 3, 7, 14, and 28. Serum I-FABP, antibodies to tissue transglutaminase (tTG-IgA), deamidated gliadin peptides (IgA-DGP), and anti-actin (AAA-IgA) were assessed at each visit. Villous-height to crypt-depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count were evaluated at day -14, 3, and 14. Forty-three CD-serology negative individuals were included to compare serum I-FABP levels in CD patients on a gluten-free diet (GFD) with those in healthy subjects.
Serum I-FABP levels increased significantly during a two-week GC. In contrast, the most pronounced autoantibody increase was found at day 28, when patients had already returned to a GFD for two weeks. IgA-AAA titers were only significantly elevated at day 28. I-FABP levels and IEL count correlated at baseline (r=0.458, P=0.042) and at day 14 (r=0.654, P=0.002) of GC. Neither gluten dose nor time on a GFD influenced I-FABP change during GC.
Serum I-FABP levels increased significantly during a two-week GC in adult CD patients and correlated with IEL count. The data suggest that serum I-FABP is an early marker of gluten-induced enteropathy in celiac patients and may be of use in both clinical and research settings.
麸质激发试验（GC）的反应是乳糜泻（CD）诊断算法和研究试验中的关键特征。目前，自身抗体滴度、GC反应迟缓者以及侵入性十二指肠活检用于评估麸质反应性。本研究调查了血清肠脂肪酸结合蛋白（I-FABP）（一种肠上皮损伤标志物）预测CD患者GC期间肠损伤的准确性。
20名缓解期成年CD患者接受为期两周的GC，每天摄入3克或7.5克麸质。研究访视时间为第-14天、0天、3天、7天、14天和28天。每次访视时评估血清I-FABP、组织转谷氨酰胺酶抗体（tTG-IgA）、去酰胺化麦醇溶蛋白肽（IgA-DGP）和抗肌动蛋白抗体（AAA-IgA）。在第-14天、3天和14天评估绒毛高度与隐窝深度比值（Vh:Cd）和上皮内淋巴细胞（IEL）计数。纳入43名CD血清学阴性个体，比较CD患者无麸质饮食（GFD）时与健康受试者的血清I-FABP水平。
在为期两周的GC期间，血清I-FABP水平显著升高。相比之下，自身抗体最显著的升高出现在第28天，此时患者已恢复GFD两周。IgA-AAA滴度仅在第28天显著升高。GC基线时（r=0.458，P=0.042）和第14天（r=0.654，P=0.002），I-FABP水平与IEL计数相关。GC期间，麸质剂量和GFD时间均未影响I-FABP变化。
成年CD患者在为期两周的GC期间，血清I-FABP水平显著升高，并与IEL计数相关。数据表明，血清I-FABP是乳糜泻患者麸质诱导性肠病的早期标志物，可能在临床和研究环境中均有用处。
