Tag Archives: EMA

Likelihood of Celiac Disease with Conflicting Serology Results

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R Mandile et al. J Pediatr Gastroenterol Nutr. 2025;81:1482–1487. Advantages of anti-endomysial evaluation in children with low titers of anti-transglutaminase antibodies: A retrospective study

This was a single center retrospective study examining children (n=202) undergoing EGD (2022-2024) to evaluate for celiac. Among those with low anti-TTG IgA titers, Group 1 (n=25) was EMA negative and Group 2 (n=100) was EMA positive.

Key findings:

  • The finding of discordant serology (anti-transglutaminase [anti-TG] positive and EMA negative) is infrequent (12% cases, 25 out of 202), and all patients with discordant serology had anti-TG positive at low titer (<4 times the upper limit of normality).
  • Group 1 (N = 25) had a mean anti-TG titer of 1.86× ULN and villous atrophy (VA) in only 8% (2/25). Group 2 (N = 100) had VA in 35% (35/100)
Percentage of patients with villous atrophy between EMA positive and EMA negative children.

Discussion Points:

  • The diagnosis of CD still requires performing an EGD in at least half of the cases
  • This “study suggests that patients with low levels of anti-TG but EMA positive antibodies should anyway receive an EGDS in the next 6 months, since in around one-third of the cases a duodenal atrophy will be detected”
  • In those with low anti-TG but EMA negative, ” it could be reasonable to initially follow-up patients over time with clinical and serological monitoring (in particular of anti-TG titer), postponing the EGDS to a later stage, when the disease is more advanced and the chance of finding a concomitant VA (and thus the need to start a GFD) is higher”

My take: In patients with minimal symptoms and low level anti-TG, my strategy has been to follow with serological monitoring and if repeatedly abnormal, proceed with endoscopy. This study suggests that obtaining EMA early may influence choice to proceed earlier with endoscopy.

Related blog posts

Is a biopsy necessary in Celiac disease?

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Yes, at least for now.  That is the conclusion of a recent editorial (JPGN 2012; 54: 310-11) regarding Kurpa et al (JPGN 2012; 54: 387-91).  The article by Kurpa et al discusses the utility of the ESPGHAN criteria for diagnosis of celiac disease.  Among the patients with strongly positive TTG (> 100 units), 94% had a diagnosis of Celiac disease confirmed with biopsy; in addition, this result correlated well with positive endomysial antibody and with positive DQ2/8. In those with TTG (30-99 units), Celiac disease was diagnosed in 69% of children and 86% of adults.

Additional references:

  • -JPGN 2011;52: 554. May not need to biopsy if TTG >100 & responds to GFD
  • -Clin Gastro & Hep 2011; 9: 320. Nat’l hx in children with +serology. n=106. 33% developed villous atrophy c/in 2 yrs.
  • -Gastroenterology 2010; 139: 763. Mortality NOT worsened in undiagnosed celiac dz in Olmstead County, though bone density decreased. n=129 of 16,847. (?milder cases undiagnosed)
  • -J Pediatr 2010; 157: 373, 353. Even pts w/o villous atrophy & +serology, benefited from GFD with regard to GI symptoms and serological markers.
  • -JPGN 2010; 50: 397. n=250. +association
  • -Mohamed BM, et al. The Absence of a Mucosal Lesion on Standard Histological Examination Does Not Exclude Diagnosis of Celiac Disease.  Dig Dis Sci. 2007 May 9;
  • -JPGN 2009; 49: 52. deamidated gliadin -new, accurate biomarker for celiac. n=302.
  • -Gastroenterology 2009; 137: 88. Increased mortality in undiagnosed celiac –4-fold increase. Also, increasing prevalence ~4 fold in last 50 yrs.
  • -Gastroenterology 1967; 52: 893-897. Seminal article ‘gluten as culprit in celiac’
  • -Gastroenterology 2009; 136: 816. Mild enteropathy w Celiac –still needs GFD
  • -JPGN 2008; 47: 618. duodenal bulb always abnl, n=665
  • -Clin Gastro & Hep 2008; 6: 753. Incidence of autoimmune diseases less in those compliant with diet. n=178.
  • -Clinical Gastro & Hep 2008; 6: 426. Usefulness of deamidated gliadin antibodies (about as useful as TTG). In this study with n=216 celiac pts and 124 controls, TTG had sensitivity of 78% and 98% specificity.
  • -JPGN 2007; 45: 497. ~1% of UK kids c celiac; 90% missed. Avon study (ALSPAC). n=5470 screened from cohort of 13,971
  • -NEJM 2007; 357: 1731. Nice review which suggests the introduction of gluten 4-7 months in healthy infants. HLA DQ2 present in 90-95%; HLA DQ8 in remainder. Both also present in gen population, 30-40%. Scalloping of mucosal folds often seen. Can stain bx for CD3, CD8 receptors. More refractory cases stain only for CD3 (neg for CD8).