Pathology. 2020 Aug;52(5):568-575. doi: 10.1016/j.pathol.2020.05.002. Epub 2020 Jun 22.

Grace Thompson ¹, Zubin Grover ², Richard Loh ³, Catherine Mews ², Madhur Ravikumara ², Gareth Jevon ⁴, Lloyd D'Orsogna ⁵, Andrew McLean-Tooke ⁶

Author information

• ¹Department of Clinical Immunology, PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia. Electronic address: Grace.thompson@health.wa.gov.au.
• ²Department of Gastroenterology, Perth Children's Hospital, Perth, WA, Australia.
• ³Department of Clinical Immunology, PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.
• ⁴Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth Children's Hospital, Perth, WA, Australia.
• ⁵Department of Clinical Immunology, PathWest Laboratory Medicine, Fiona Stanley Hospital, Perth, WA, Australia.
• ⁶Department of Clinical Immunology, PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia; Department of Immunology, Perth Children's Hospital, Perth, WA, Australia.

Abstract

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.