Thompson Grace, Grover Zubin, Loh Richard, Mews Catherine, Ravikumara Madhur, Jevon Gareth, D'Orsogna Lloyd, McLean-Tooke Andrew
Department of Clinical Immunology, PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.
Department of Gastroenterology, Perth Children's Hospital, Perth, WA, Australia.
Pathology. 2020 Aug;52(5):568-575. doi: 10.1016/j.pathol.2020.05.002. Epub 2020 Jun 22.
Coeliac disease (CD) diagnosis is based on clinical assessment, detection of specific autoantibodies and histological examination of small intestinal biopsies. The European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines have recently been updated and recommend CD may be diagnosed without a biopsy or HLA typing in symptomatic patients with high titre IgA tissue transglutaminase antibodies (aTTG) and positive endomysial antibodies (EMA). However, the need for EMA in patients with high level aTTG has been questioned. We aimed to determine the diagnostic benefit of HLA typing, EMA and IgG antibodies to deamidated gliadin (DGP) in children with high level aTTG. We prospectively evaluated children presenting for assessment of possible CD. All patients underwent small bowel biopsy, serological testing and HLA typing. Results were analysed and correlated with histopathological diagnosis. A total of 209 children were assessed; 61.5% were found to have CD and 29% could have avoided biopsy as per 2020 ESPGHAN guidelines. Titres of aTTG ≥60 U/mL or DGP ≥28 U/mL gave 100% specificity and 100% positive predictive value (PPV) for CD. HLA typing and EMA did not improve the PPV of patients with aTTG ≥60 U/mL, but addition of DGP ≥28 U/mL improved diagnostic sensitivity whilst retaining 100% specificity. Addition of HLA and EMA testing in patients with high titre aTTG antibodies does not improve diagnostic performance and may possibly be omitted from the serological workup in these patients. Our data support combining aTTG and DGP testing and optimising cut-offs to maximise specificity as an alternative biopsy-free diagnostic approach.
乳糜泻（CD）的诊断基于临床评估、特定自身抗体的检测以及小肠活检的组织学检查。欧洲儿科胃肠病学、肝病学和营养学会（ESPGHAN）指南最近进行了更新，建议在有症状且抗组织转谷氨酰胺酶抗体（aTTG）滴度高和肌内膜抗体（EMA）阳性的患者中，无需活检或HLA分型即可诊断CD。然而，对于aTTG水平高的患者是否需要检测EMA存在疑问。我们旨在确定HLA分型、EMA以及抗去酰胺化麦醇溶蛋白（DGP）IgG抗体在aTTG水平高的儿童中的诊断价值。我们对前来评估可能患有CD的儿童进行了前瞻性评估。所有患者均接受了小肠活检、血清学检测和HLA分型。对结果进行分析并与组织病理学诊断进行关联。共评估了209名儿童；根据2020年ESPGHAN指南，61.5%的儿童被诊断为患有CD，29%的儿童可以避免活检。aTTG≥60 U/mL或DGP≥28 U/mL对CD的特异性为100%，阳性预测值（PPV）为100%。HLA分型和EMA并未提高aTTG≥60 U/mL患者的PPV，但加入DGP≥28 U/mL可提高诊断敏感性，同时保持100%的特异性。在aTTG抗体滴度高的患者中加入HLA和EMA检测并不能提高诊断性能，在这些患者的血清学检查中可能可以省略。我们的数据支持将aTTG和DGP检测相结合并优化临界值以最大化特异性，作为一种无需活检的替代诊断方法。
