Background

The serological screening for celiac disease (CD) is currently based on the detection of anti-transglutaminase (tTG) IgA antibodies, subsequently confirmed by positive endomysial antibodies (EMA). When an anti-tTG IgA positive/EMA IgA negative result occurs, it can be due either to the lower sensitivity of the EMA test or to the lower specificity of the anti-tTG test. This study aimed at verifying how variation in analytical specificity among different anti-tTG methods could account for this discrepancy.

Methods

A total of 130 consecutive anti-tTG IgA positive/EMA negative samples were collected from the local screening routine and tested using five anti-tTG IgA commercial assays: two chemiluminescence methods, one fluoroimmunoenzymatic method, one immunoenzymatic method and one multiplex flow immunoassay method.

Results

Twenty three/130 (17.7%) patients were diagnosed with CD. In the other 107 cases a diagnosis of CD was not confirmed. The overall agreement among the five anti-tTG methods ranged from 28.5% to 77.7%. CD condition was more likely linked to the positivity of more than one anti-tTG IgA assay (monopositive = 2.5%, positive with ≥ three methods = 29.5%; p = 0.0004), but it was not related to anti-tTG IgA antibody levels (either positive or borderline; p = 0.5).

Conclusions

Patients with positive anti-tTG/negative EMA have a low probability of being affected by CD. Given the high variability among methods to measure anti-tTG IgA antibodies, anti-tTG-positive/EMA-negative result must be considered with extreme caution. It is advisable that the laboratory report comments on any discordant results, suggesting to consider the data in the proper clinical context and to refer the patient to a CD reference center for prolonged follow up.

中文翻译：

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组织转谷氨酰胺酶抗体阳性，肌内膜抗体阴性：乳糜泻诊断中未解决的问题

背景

乳糜泻 (CD) 的血清学筛查目前基于抗转谷氨酰胺酶 (tTG) IgA 抗体的检测，随后由阳性肌内膜抗体 (EMA) 确认。当出现抗 tTG IgA 阳性/EMA IgA 阴性结果时，可能是由于 EMA 检测的敏感性较低或抗 tTG 检测的特异性较低。本研究旨在验证不同抗 tTG 方法之间分析特异性的差异如何解释这种差异。

方法

从本地筛选程序中收集了总共 130 个连续的抗 tTG IgA 阳性/EMA 阴性样品，并使用五种抗 tTG IgA 商业化验进行测试：两种化学发光方法、一种荧光免疫酶法、一种免疫酶法和一种多重流动免疫测定法。

结果

23/130 (17.7%) 患者被诊断为 CD。在其他 107 例中，CD 的诊断没有得到确认。五种抗 tTG 方法之间的总体一致性范围从 28.5% 到 77.7%。CD 状况更可能与一种以上抗 tTG IgA 检测的阳性有关（单阳性 = 2.5%，≥ 三种方法阳性 = 29.5%；p  = 0.0004），但与抗 tTG IgA 抗体水平无关（阳性或临界值；p  = 0.5）。

结论

抗 tTG 阳性/EMA 阴性的患者受 CD 影响的可能性较低。鉴于测量抗 tTG IgA 抗体的方法之间的高度可变性，必须极其谨慎地考虑抗 tTG 阳性/EMA 阴性结果。建议实验室报告对任何不一致的结果进行评论，建议在适当的临床背景下考虑数据并将患者转诊至 CD 参考中心进行长期随访。