Immunology Division, Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Australia.
Murdoch Children's Research Institute, Parkville, Australia.
United European Gastroenterol J. 2020 Feb;8(1):108-118. doi: 10.1177/2050640619874173. Epub 2019 Sep 3.
Diagnosing coeliac disease (CD) in patients on a gluten-free diet (GFD) is difficult. Ingesting gluten elevates circulating interleukin (IL)-2, IL-8 and IL-10 in CD patients on a GFD.
We tested whether cytokine release after gluten ingestion differentiates patients with CD from those with self-reported gluten sensitivity (SR-GS).
Australian patients with CD ( = 26) and SR-GS ( = 18) on a GFD consumed bread (estimated gluten 6 g). Serum at baseline and at 3 and 4 h was tested for IL-2, IL-8 and IL-10. Separately, Norwegian SR-GS patients ( = 49) had plasma cytokine assessment at baseline and at 2, 4 and 6 h after food bars containing gluten (5.7 g), fructan or placebo in a previous double-blind crossover study.
Gluten significantly elevated serum IL-2, IL-8 and IL-10 at 3 and 4 h in patients with CD but not SR-GS. The highest median fold-change from baseline at 4 h was for IL-2 (8.06, IQR: 1.52-24.0; < 0.0001, Wilcoxon test). The two SR-GS cohorts included only one (1.5%) confirmed IL-2 responder, and cytokine responses to fructan and placebo were no different to gluten. Overall, cytokine release after gluten was present in 22 (85%) CD participants, but 2 of the 4 non-responders remained clinically well after 1 y on an unrestricted diet. Hence, cytokine release occurred in 22 (92%) of 24 'verified' CD participants.
Gluten challenge with high-sensitivity cytokine assessment differentiates CD from SR-GS in patients on a GFD and identifies patients likely to tolerate gluten reintroduction. Systemic cytokine release indicating early immune activation by gluten in CD individuals cannot be detected in SR-GS individuals.
在遵循无麸质饮食（GFD）的患者中诊断乳糜泻（CD）具有一定难度。在遵循 GFD 的 CD 患者中，摄入麸质会使循环中的白细胞介素（IL）-2、IL-8 和 IL-10 升高。
我们检测了麸质摄入后的细胞因子释放是否可以区分 CD 患者和自述麸质敏感（SR-GS）患者。
澳大利亚的 CD（n=26）和 SR-GS（n=18）患者在遵循 GFD 的情况下摄入面包（估计含有 6 g 麸质）。分别检测基线和 3、4 小时时的血清中 IL-2、IL-8 和 IL-10。此外，在之前的一项双盲交叉研究中，49 名挪威 SR-GS 患者在食用含有麸质（5.7 g）、果糖或安慰剂的食物棒后，分别在基线和 2、4 和 6 小时进行了血浆细胞因子评估。
麸质可显著升高 CD 患者 3、4 小时时的血清 IL-2、IL-8 和 IL-10，但对 SR-GS 患者无此作用。4 小时时 IL-2 的中位数最高变化倍数为 8.06（IQR：1.52-24.0； < 0.0001，Wilcoxon 检验）。两个 SR-GS 队列中仅各有 1 名（1.5%）确认为 IL-2 应答者，且果糖和安慰剂的细胞因子反应与麸质无差异。总体而言，24 名“确诊”CD 患者中有 22 名（85%）在摄入麸质后出现细胞因子释放，但在无限制饮食 1 年后，4 名无应答者中有 2 名仍保持临床良好状态。因此，24 名“确诊”CD 患者中有 22 名（92%）出现细胞因子释放。
在遵循 GFD 的患者中进行高灵敏度细胞因子检测的麸质挑战可区分 CD 和 SR-GS，并可识别出可能耐受麸质再引入的患者。在 SR-GS 患者中，无法检测到 CD 个体中早期由麸质引起的全身性细胞因子释放，表明存在免疫激活。
