Alina Popp1,2,3, Taina Arvola4,5, Juha Taavela1,2,6, Laura Kivelä1,2, Adina Ene3, Kaija Laurila1,2, Päivi Saavalainen7, Markku Mäki1,2, Kalle Kurppa1,2,8,3. 1. Centre for Child Health Research, Tampere University. 2. Department of Pediatrics, Tampere University Hospital. 3. National Institute for Mother and Child Health, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania. 4. Allergy Centre, Tampere University Hospital, Tampere. 5. Hämeenlinna Central Hospital, Hämeenlinna. 6. Central Finland Central Hospital, Jyväskylä. 7. Research Programs Unit, Immunobiology and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki. 8. The University Consortium of Seinäjoki, Seinäjoki, Finland.
Abstract
GOALS: To test the accuracy of serology-based criteria for diagnosing celiac disease utilizing quantitative histomorphometry. BACKGROUND: The revised European pediatric guidelines allow noninvasive celiac disease diagnosis for a subgroup of children. However, in some of the studies on this issue, the positive predictive value (PPV) of serology has remained suboptimal, possibly because of challenges of histopathology as the reference standard. STUDY: Prospectively enrolled children with transglutaminase 2 antibodies (TGA) above the upper limit of normal (ULN) underwent blood sampling and duodenal biopsy in Finland and Romania. Those with TGA ≥10× ULN, positive endomysium antibodies (EmA), and disease-associated genetics were considered to fulfill triple criteria for celiac disease. Initial histopathologic analysis was conducted using grouped classification, whereupon centralized morphometry was performed. RESULTS: Altogether 88 (54%) children were triple positive. In local evaluation, 99% of triple-positive children and 73% of children with TGA <10× ULN had celiac disease. These figures increased to 100% and 85% after more precise morphometric analysis. Triple-positive children had more anemia and higher median EmA and liver enzyme values than those with TGA<10× ULN; the groups were comparable in other clinical features and laboratory parameters. CONCLUSIONS: When applied as recommended, the nonbiopsy strategy had already yielded excellent PPV regardless of the site of diagnosis or clinical presentation in the local analysis. PPV further increased to 100% with standardized duodenal morphometry.
GOALS: To test the accuracy of serology-based criteria for diagnosing celiac disease utilizing quantitative histomorphometry. BACKGROUND: The revised European pediatric guidelines allow noninvasive celiac disease diagnosis for a subgroup of children. However, in some of the studies on this issue, the positive predictive value (PPV) of serology has remained suboptimal, possibly because of challenges of histopathology as the reference standard. STUDY: Prospectively enrolled children with transglutaminase 2 antibodies (TGA) above the upper limit of normal (ULN) underwent blood sampling and duodenal biopsy in Finland and Romania. Those with TGA ≥10× ULN, positive endomysium antibodies (EmA), and disease-associated genetics were considered to fulfill triple criteria for celiac disease. Initial histopathologic analysis was conducted using grouped classification, whereupon centralized morphometry was performed. RESULTS: Altogether 88 (54%) children were triple positive. In local evaluation, 99% of triple-positive children and 73% of children with TGA <10× ULN had celiac disease. These figures increased to 100% and 85% after more precise morphometric analysis. Triple-positive children had more anemia and higher median EmA and liver enzyme values than those with TGA<10× ULN; the groups were comparable in other clinical features and laboratory parameters. CONCLUSIONS: When applied as recommended, the nonbiopsy strategy had already yielded excellent PPV regardless of the site of diagnosis or clinical presentation in the local analysis. PPV further increased to 100% with standardized duodenal morphometry.
Authors: Johannes Virta; Markus Hannula; Katri Lindfors; Ilmari Tamminen; Juha Taavela; Heini Huhtala; Katri Kaukinen; Päivi Saavalainen; Jari Hyttinen; Kalle Kurppa Journal: Front Immunol Date: 2022-09-23 Impact factor: 8.786