For adults from populations with less than a 5% prevalence of celiac disease, all guidelines recommend following serology with confirmatory biopsy, and the experts concur. If biopsy was part of the initial work-up, they recommend performing confirmatory serology before starting a gluten-free diet. If the biopsy was negative but celiac disease is strongly suspected, they recommend TG2-IgA testing followed by repeat biopsies, when possible, either at the same time or in the future.
For children with suspected celiac disease, the North American Society for Pediatric Gastroenterology Hepatology and Nutrition recommends starting with biopsy, while the European Society for Paediatric Gastroenterology Hepatology and Nutrition suggests starting with quantitative TG2-IgA testing, followed by TG2-IgA, EMA, or HLA-DQ2/DQ8 assays if TG2-IgA is 10 times higher than the upper limit of normal. However, EGD with biopsies and even a gluten challenge may be needed if serology results are unclear, the experts state. They recommend against gluten-free or low-gluten diets prior to diagnosis, since these can lower the sensitivity of both histology and serology. If a patient has unclear test results and is already on a gluten-free diet, they suggest resuming eating three slices of wheat bread daily for 1-3 months, followed by TG2-IgA testing.
A small but important subgroup of patients have strong suspicion for celiac disease but are negative on IgA isotype tests because of IgA deficiency. In such suspected cases, the experts recommend measuring total IgA, IgG deamidated gliadin antibodies, and TG2-IgG levels. They note that IgG isotype testing for TG2 antibodies is not celiac specific outside the setting of IgA deficiency.
Serology has a useful but more limited role in managing celiac disease, according to the practice update. Negative TG2-IgA and other serology does not guarantee that the intestinal mucosa has healed, so patients with ongoing or relapsing symptoms without another obvious cause should have repeat biopsies. However, serology that stays positive over time usually indicates ongoing mucosal damage and gluten exposure, so these follow-up tests are appropriate 6 and 12 months after diagnosing celiac disease and yearly thereafter.
Dr. Husby reported receiving grant support from the University of Southern Denmark, the Region of Southern Denmark, and the Novo Nordisk Research Fund. He also reported receiving payments from Thermo Fisher Scientific and an advisory relationship with Inova. Two coauthors reported ties to Alba Therapeutics, Celimmune, Intrexon, GlaxoSmithKline, and several other pharmaceutical companies.
SOURCE: Husby S et al. Gastroenterology. 2018 Dec 19. doi: 10.1053/j.gastro.2018.12.010.