Department of Laboratory Medicine, OLV Hospital, Aalst, Belgium; Department of Laboratory Medicine, University Hospital Leuven, Leuven, Belgium.
Department of Laboratory Medicine, Europe Hospitals, Brussels, Belgium.
Autoimmun Rev. 2020 May;19(5):102513. doi: 10.1016/j.autrev.2020.102513. Epub 2020 Mar 12.
The clinical presentation of celiac disease (CD) varies between children. The objective of this study was to document the pre-test probability for CD based on symptoms and routine laboratory test and to evaluate the performance of two IgA anti-tissue transglutaminase (tTG) assays. We critically reviewed the concept of using multiples of the manufacturer's upper limit of normal (ULN), as proposed in the ESPGHAN guidelines (if IgA tTG is >10 times ULN, no biopsy is needed).
The retrospective study included 91 children with newly diagnosed CD and 605 controls (<16 years). All underwent upper endoscopy with small bowel biopsies. Four laboratory parameters and 16 symptoms were registered. All patients were tested for IgA anti-tTG antibodies with assays from Inova Diagnostics and Thermo Fisher Scientific.
Some combinations of clinical symptoms and laboratory parameters had a high pre-test probability for CD, such as (combinations of) anorexia, failure to thrive, low ferritin level and elevated AST. The diagnostic performance of both IgA anti-tTG assays was excellent and comparable (no difference in ROC curve area under the curve). At a threshold that corresponds to a specificity of 100% (5 times ULN for Inova Diagnostics and 2 times ULN for Thermo Fisher), the sensitivity was 82% for both assays. At the 10 times ULN threshold, the sensitivity differed between the assays (77% vs. 57%), indicating that such threshold does not completely align interpretation across companies.
Our study showed that some combinations of symptoms and aberrant laboratory parameters had a high pre-test probability. The use of the ESPGHAN non-biopsy approach could reduce small bowel biopsies, but thresholds for IgA-tTG levels are not aligned across assays and should be based on predefined likelihood ratios or specificity.
乳糜泻（CD）的临床表现在儿童之间存在差异。本研究的目的是记录基于症状和常规实验室检查的 CD 先验概率，并评估两种 IgA 抗组织转谷氨酰胺酶（tTG）检测的性能。我们批判性地回顾了 ESPGHAN 指南中提出的使用制造商正常值上限（ULN）倍数的概念（如果 IgA tTG 大于 10 倍 ULN，则无需进行活检）。
这项回顾性研究纳入了 91 例新诊断为 CD 的儿童和 605 例对照者（年龄<16 岁）。所有患者均接受了上消化道内镜检查和小肠活检。记录了 4 项实验室参数和 16 种症状。所有患者均接受了 Inova Diagnostics 和 Thermo Fisher Scientific 公司的 IgA 抗 tTG 抗体检测。
一些临床症状和实验室参数的组合对 CD 具有较高的先验概率，例如（组合）厌食、生长不良、低铁蛋白水平和升高的天冬氨酸氨基转移酶（AST）。两种 IgA 抗 tTG 检测的诊断性能均优异且相当（ROC 曲线下面积无差异）。在一个特异性为 100%的阈值（Inova Diagnostics 为 5 倍 ULN，Thermo Fisher 为 2 倍 ULN），两种检测的敏感性均为 82%。在 10 倍 ULN 阈值时，两种检测的敏感性存在差异（77% vs. 57%），表明该阈值不能完全在不同公司之间统一解释。
本研究表明，一些症状和异常实验室参数的组合具有较高的先验概率。ESPAGHN 非活检方法的应用可以减少小肠活检，但 IgA-tTG 水平的阈值在不同检测中不一致，应基于预设的似然比或特异性。
