Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts

Abstract

Objective: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.

Design: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD.

Results: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively.

Conclusion: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

Keywords: coeliac disease.

Figure 1

(A) Demographic and clinical details of the patients in cohort 1. GI symptoms include abdominal pain, dyspepsia, dysphagia, nausea, vomiting, bloating and constipation; extraintestinal symptoms include ataxia, headache, dizziness, fatigue, joint pain and skin rash; malabsorptive symptoms include diarrhoea, haematinic deficiencies with/without anaemia and weight loss. (B) Normalised tTG titres against Marsh grade in patients from cohort 1. Horizontal bar represents the mean; error bars denote SE of the mean. Black dotted line represents 1×ULN threshold; red dotted line represents 10×ULN threshold. Comparisons between groups made with Kruskal-Wallis and post hoc Dunn test. (C) Performance characteristics of tTG titres of 10×ULN at predicting villous atrophy. ****P<0.0001. tTG, tissue transglutaminase; ULN, upper limit of normal; PPV, positive predictive value; NPV, negative predictive value.

Figure 2

(A) Demographic and clinical details of the patients in cohorts 1A and 1B. (B) tTG titres against Marsh grade in patients from cohort 1A. (C) tTG titres against Marsh grade in patients from cohort 1B. Horizontal bar represents the mean; error bars denote SE of the mean. Black dotted line represents 1×ULN threshold; red dotted line represents 10×ULN threshold. Comparisons between groups were made with analysis of variance and post hoc Tukey test. (D) Performance characteristics of tTG titres of 10×ULN at predicting villous atrophy. **P<0.01, ****P<0.0001. tTG, tissue transglutaminase; ULN, upper limit of normal; PPV, positive predictive value; NPV, negative predictive value.

Figure 3

(A) Demographic and clinical details of the patients in cohort 2. GI symptoms include abdominal pain, dyspepsia, dysphagia, nausea, vomiting, bloating and constipation; extraintestinal symptoms include ataxia, headache, dizziness, fatigue, joint pain and skin rash; malabsorptive symptoms include diarrhoea, haematinic deficiencies with/without anaemia and weight loss. (B) tTG titres against Marsh grade in patients from cohort 2. Horizontal bar represents the mean; error bars denote SE of the mean. Black dotted line represents 1×ULN threshold; red dotted line represents 10×ULN threshold. Comparisons between groups were made with analysis of variance and post hoc Tukey test. (C) Performance characteristics of tTG titres of 10×ULN at predicting villous atrophy. ****P<0.0001. tTG, tissue transglutaminase; ULN, upper limit of normal; PPV, positive predictive value; NPV, negative predictive value.

Figure 4

(A) Receiver operating characteristic curve analysis of tTG values against Marsh 3 histology in cohort 2. (B) Performance characteristics of tTG titres×5.9 ULN at predicting Marsh 3 lesions. tTG, tissue transglutaminase; ULN, upper limit of normal; PPV, positive predictive value; NPV, negative predictive value.

Figure 5

(A) Demographic and clinical details of the patients in cohort 3. GI symptoms include abdominal pain, dyspepsia, dysphagia, nausea, vomiting, bloating and constipation; extraintestinal symptoms include ataxia, headache, dizziness, fatigue, joint pain and skin rash; malabsorptive symptoms include diarrhoea, haematinic deficiencies with/without anaemia and weight loss. (B) Normalised tTG titres against Marsh grade in patients from cohort 3. Horizontal bar represents the mean; error bars denote SE of the mean. Black dotted line represents 1×ULN threshold; red dotted line represents 10×ULN threshold. Comparisons between groups made with Kruskal-Wallis and post hoc Dunn test. (C) Performance characteristics of tTG titres of 10×ULN at predicting villous atrophy. **P<0.01. tTG, tissue transglutaminase; ULN, upper limit of normal; PPV, positive predictive value; NPV, negative predictive value.