Advertisement

Immunohistologic analysis of the duodenal bulb: a new method for celiac disease diagnosis in children

      Background and Aims

      Anti-tissue transglutaminase antibodies (anti-tTG) have simplified celiac disease (CD) diagnosis. However, in atypical forms of CD, intestinal biopsy sampling is still required. This prospective study investigates whether histologic analysis of the duodenal bulb combined with intestinal IgA anti-tTG deposit immunoassay makes CD diagnosis possible in at-risk children with low concentrations of serum anti-tTG.

      Methods

      Histologic and intestinal IgA anti-tTG deposit immunoassays were used.

      Results

      Two hundred forty-five symptomatic children positive for serum anti-tTG (>7 U/mL) were enrolled and divided into 3 groups: extensive duodenal atrophy (n = 209), with IgA anti-tTG deposits throughout the duodenum and high serum anti-tTG concentrations (157 ± 178 U/mL); bulb duodenal atrophy (n = 22), with widespread IgA anti-tTG deposits in 9 and in the bulb alone in 13 and low serum anti-tTG concentrations (13.9 ± 8.7 U/mL); and normal duodenum (n = 14), with widespread IgA anti-tTG deposits in 8 and in the bulb alone in 6 and low serum anti-tTG concentrations (10.6 ± 6.2 U/mL). All patients in the first 2 groups were diagnosed with CD and 8 from the third group. All improved after 1 year of gluten-free diet. Bulb duodenal analysis led to a 12% (30/245) increase in CD diagnosis. No CD-related lesions were observed in the 30 control subjects.

      Conclusions

      In children at risk for CD, bulb duodenum biopsy sampling is essential to identify villous atrophy and detect IgA anti-tTG deposits even in absence of intestinal lesions. These mucosal autoantibodies could well represent a new standard for diagnosing CD.

      Abbreviations:

      AEA (anti-endomysium antibodies), anti-tTG (anti-tissue transglutaminase antibodies), CD (celiac disease), GFD (gluten-free diet), HLA (human leucocyte antigen), IEL (intraepithelial lymphocyte)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Gastrointestinal Endoscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Green P.H.R.
        • Cellier C.
        Celiac disease.
        N Engl J Med. 2007; 357: 1731-1743
        • Marzari R.
        • Sblattero D.
        • Florian F.
        • et al.
        Molecular dissection of the tissue transglutaminase autoantibody response in celiac disease.
        J Immunol. 2001; 166: 4170-4176
        • Lewis N.R.
        • Scott B.B.
        Systematic review: the use of serology to exclude or diagnose coeliac disease (a comparison of the endomysial and tissue transglutaminase antibody tests).
        Aliment Pharmacol Ther. 2006; 24: 47-54
        • Trevisiol C.
        • Ventura A.
        • Baldas V.
        • et al.
        A reliable screening procedure for coeliac disease in clinical practice.
        Scand J Gastroenterol. 2002; 37: 679-684
        • Husby S.
        • Koletzko I.R.
        • Korponay-Szabó M.L.
        • et al.
        European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.
        J Pediatr Gastroenterol Nutr. 2012; 54: 136-160
        • Werkstetter K.
        • Korponay-Szabó I.
        • Popp A.
        • et al.
        Accuracy in diagnosis of celiac disease without biopsies in clinical practice.
        Gastroenterology. 2017; 153: 924-935
        • Kurien M.
        • Evans K.E.
        • Hopper A.D.
        • et al.
        Duodenal bulb biopsies for diagnosing adult celiac disease: Is there an optimal biopsy site?.
        Gastrointest Endosc. 2012; 75: 1190-1196
        • Taavela J.
        • Popp A.
        • Korponay-szabo I.R.
        • et al.
        A prospective study on the usefulness of duodenal bulb biopsies in celiac disease diagnosis in children: urging caution.
        Am J Gastroenterol. 2016; 111: 124-133
        • Not T.
        • Ziberna F.
        • Vatta S.
        • et al.
        Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet.
        Gut. 2011; 60: 1487-1493
        • Oberhuber G.
        • Granditsch G.
        • Vogelsang H.
        The histopathology of coeliac disease: time for a standardized report scheme for pathologists.
        Eur J Gastroenterol Hepatol. 1999; 11: 1185-1194
        • Corazza G.R.
        • Villanacci V.
        • Zambelli C.
        • et al.
        Comparison of the interobserver reproducibility with different histologic criteria used in celiac disease.
        Clin Gastroenterol Hepatol. 2007; 5: 838-843
        • Korponay-Szabo I.R.
        In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies.
        Gut. 2004; 53: 641-648
        • De Leo L.
        • Quaglia S.
        • Ziberna F.
        • et al.
        Serum anti-tissue transglutaminase antibodies detected during febrile illness may not be produced by the intestinal mucosa.
        J Pediatr. 2015; 166: 761-763
        • Repo M.
        • Lindfors K.
        • Mäki M.
        • et al.
        Anemia and iron deficiency in children with potential celiac disease.
        J Pediatr Gastroenterol Nutr. 2017; 64: 56-62
        • Auricchio R.
        • Tosco A.
        • Piccolo E.
        • et al.
        Potential celiac children: 9-year follow-up on a gluten-containing diet.
        Am J Gastroenterol. 2014; 109: 913-921
        • Borrelli M.
        • Maglio M.
        • Korponay-Szabò I.
        • et al.
        Intestinal anti-transglutaminase2 IgA deposits in children at risk for coeliac disease: data from the Prevent CD study.
        Clin Exp Immunol. 2018; 191: 311-317
        • Gonzalez S.
        • Gupta A.
        • Cheng J.
        • et al.
        Prospective study of the role of duodenal bulb biopsies in the diagnosis of celiac disease.
        Gastrointest Endosc. 2010; 72: 758-765

      Linked Article

      • Intestinal IgA tTG deposits in the duodenal bulb in patients with celiac disease: light at the beginning of the tunnel!
        Gastrointestinal EndoscopyVol. 88Issue 6
        • Preview
          We read with interest the article by De Leo et al1 and found it worth discussing. The authors show that immunohistologic analysis of the duodenal bulb helps in the diagnosis of celiac disease (CD) in children, even in the absence of intestinal changes, and that mucosal immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG) deposits may represent a new standard for diagnosing celiac disease. IgA anti-tTG deposits were confined to the bulb only in a higher proportion of patients with normal duodenal histologic features (43%) in comparison with patients with bulb-only atrophy (13%) and extensive duodenal atrophy (2%).
        • Full-Text
        • PDF