Negative serology not a reliable indicator of mucosal healing in celiac disease

Do not use negative serology as a reliable indicator of mucosal healing in patients with celiac disease who have persistent symptoms. Instead perform endoscopic biopsies to evaluate healing, recommends the American Gastroenterological Association (AGA) in a clinical practice update on the role of serology and histology in monitoring celiac disease.

The key recommendations are:

  • Serology is a crucial component of the detection and diagnosis of CD, particularly tissue transglutaminase-immunoglobulin A (TG2-IgA), IgA testing, and less frequently, endomysial IgA testing.
  • Thorough histological analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry is important for diagnosis and for differential diagnosis. A strongly positive TG2-IgA combined with a positive endomysial antibody in a second blood sample increases the positive predictive value for CD to virtually 100%.
  • Negative IgA isotype testing despite strong suspicion may be explained by IgA deficiency. Measuring total IgA levels, IgG deamidated gliadin antibody tests, and TG2-IgG testing in such cases.
  • IgG isotype testing for TG2 antibody is not specific in the absence of IgA deficiency.
  • In patients found to have CD first by intestinal biopsies, confirm by celiac-specific serology before starting gluten-free diet (GFD).
  • In patients with strong suspicion of CD but negative biopsies, TG2-IgA should still be performed and, if positive, repeat biopsies might be considered either at that time or sometime in the future.
  • Reduction or avoidance of gluten before diagnostic testing is discouraged, as it may reduce the sensitivity of both serology and biopsy testing.
  • When patients have already started on a GFD before diagnosis, the patient are suggested to go back on a normal diet with 3 slices of wheat bread daily preferably for 1 to 3 months before repeat determination of TG2-IgA.
  • HLA-DQ2/DQ8 has a limited role in diagnosis.Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of CD; especially as very young children before the introduction of celiac-specific serology.
  • Celiac serology has a guarded role in the detection of continued intestinal injury, in particular as to sensitivity, as negative serology in a treated patient does not guarantee that the intestinal mucosa has healed. Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure. Follow-up serology should be performed 6 and 12 months after diagnosis, and then every year.
  • Patients with persistent or relapsing symptoms, without other obvious explanations for those symptoms, should undergo endoscopic biopsies to determine healing even in the presence of negative TG2-IgA.

(Source: Husby S, et al. AGA Clinical Practice Update on diagnosis and monitoring of celiac disease-changing utility of serology and histologic measures: expert review. Gastroenterology. 2019;156(4):885-89).

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