Gómez-Aguililla Sara, Farrais Sergio, López-Palacios Natalia, Arau Beatriz, Senosiain Carla, Corzo María, Fernandez-Jimenez Nora, Ruiz-Carnicer Ángela, Fernández-Bañares Fernando, González-García Bárbara P, Tristán Eva, Montero-Calle Ana, Garranzo-Asensio María, Casado Isabel, Pujals Mar, Hernández Juana María, Infante-Menéndez Jorge, Roy Garbiñe, Sousa Carolina, Núñez Concepción
Laboratorio de Investigación en Genética de enfermedades complejas, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, 28040, Spain.
Servicio de Aparato Digestivo, Hospital Universitario Fundación Jiménez Díaz, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, 28040, Spain.
BMC Med. 2025 Mar 26;23(1):182. doi: 10.1186/s12916-025-04008-y.
Diagnosing celiac disease (CD) in individuals adhering to a gluten-free diet (GFD) presents significant challenges. Current guidelines recommend a gluten challenge (GC) lasting at least 6-8 weeks, which has several limitations. Our aim was to compare four approaches previously proposed for diagnosing CD on a GFD: IL-2 serum levels, gut-homing CD8 T cells, % TCRγδ intraepithelial lymphocytes (IELs), and UBE2L3 gene expression. Additionally, we evaluated the CD8 T-cell-based method with a 3-day GC against the standard GC protocol.
We conducted a multicenter prospective quasi-experimental clinical study. Two subsets of individuals were considered: (1) 20 patients with CD previously diagnosed and 15 non-CD controls, to evaluate the first aim; (2) 41 individuals with uncertain diagnosis who were on a GFD and required GC following current clinical guidelines, to assess the second aim. All participants underwent a 3-day GC (10 g gluten/day).
Among CD patients and non-CD controls, the sensitivity and specificity of IL-2, gut-homing CD8 T cells, and UBE2L3 were 82.4% and 83.3%, 88.2% and 100%, and 52.9% and 100%, respectively. The percentage of TCRγδ IELs showed 88.2% sensitivity. In the uncertain diagnosis group, a CD8 T-cell positive response was observed in 8 of the 41 subjects.
The percentage of TCRγδ IELs and the analysis of IL-2 levels and gut-homing CD8 T cells are promising diagnostic methods for CD on a GFD. Notably, our results suggest that the CD8 T-cell assay may provide a consistent and reliable alternative to the extended GC, eliminating the need for invasive procedures to obtain duodenal samples and prolonged gluten ingestion. However, further research with larger cohorts are necessary to validate these findings and establish their definitive clinical utility.
对坚持无麸质饮食（GFD）的个体进行乳糜泻（CD）诊断面临重大挑战。当前指南推荐进行持续至少6 - 8周的麸质激发试验（GC），但该试验存在若干局限性。我们的目的是比较先前提出的四种用于在GFD状态下诊断CD的方法：白细胞介素-2（IL-2）血清水平、归巢于肠道的CD8 T细胞、%TCRγδ上皮内淋巴细胞（IELs）以及泛素结合酶E2L3（UBE2L3）基因表达。此外，我们针对基于CD8 T细胞的方法，采用为期3天的GC方案，并与标准GC方案进行了比较。
我们开展了一项多中心前瞻性准实验性临床研究。研究对象分为两个亚组：（1）20例先前已确诊的CD患者和15例非CD对照者，以评估第一个目的；（2）41例诊断不明确且正在进行GFD饮食并根据当前临床指南需要进行GC的个体，以评估第二个目的。所有参与者均接受了为期3天的GC（每天10克麸质）。
在CD患者和非CD对照者中，IL-2、归巢于肠道的CD8 T细胞和UBE2L3的敏感性和特异性分别为82.4%和83.3%、88.2%和100%、52.9%和100%。TCRγδ IELs的百分比显示出88.2%的敏感性。在诊断不明确的组中，41名受试者中有8名观察到CD8 T细胞呈阳性反应。
TCRγδ IELs的百分比以及IL-2水平和归巢于肠道的CD8 T细胞分析是在GFD状态下诊断CD的有前景的诊断方法。值得注意的是，我们的结果表明，CD8 T细胞检测可能为延长的GC提供一种一致且可靠的替代方法，无需进行侵入性操作获取十二指肠样本以及长时间摄入麸质。然而，需要更大样本量的进一步研究来验证这些发现并确定其确切的临床实用性。
