Tag Archives: ttg iga

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.

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Celiac Disease: Lower TTG-IgA Titers Associated with Isolated Duodenal Bulb Presentation

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QY Wang et al. JPGN 2025; 80:678–685. Open Access! Low TTG-IgA associated with isolated bulb pathology in pediatric celiac disease: Implications in a no-biopsy approach era

Methods: There were 405 cases included in this retrospective study (mean age = 9.6 years). TTG-IgA values were considered negative if <4 U/mL, equivocal between 4 and 10 U/mL inclusively, and positive if >10 U/mL. At the authors’ institution, TTG‐IgA ≥10× ULN corresponds to ≥100 U/mL.

Key findings:

  • Bulb-restricted CD was present in 7.4% of cases
  • TTG-IgA was negative or equivocal in 60.0% of bulb-restricted CD, compared to 5.3% of distal duodenal CD (odds ratio [OR] = 26.6
  • No bulb-restricted CD cases attained TTG-IgA ≥10× ULN, compared to 48.5% of distal duodenal CD

My take: This study confirms and quantitates what most clinicians have experienced. Isolated duodenal bulb pathology is associated with lower celiac titer abnormalities.

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Is it Helpful to Check Celiac Serology Titers After 3 Months of a Gluten Free Diet?

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A recent prospective study (D Petroff et al. Clin Gastroenterol Hepatol 2018; 16: 1442-49) with 345 pediatric patients with biopsy-proven celiac disease (CD) examined serologic response to a gluten-free diet (GFD) between 2012-2015.

Key findings:

  • Mean TTG IgA concentration decreased 14-fold after 3 months of a GFD.  The study assay used kits from EUROIMMUN.
  • TTG IgA remained above 1-fold ULN in 83.8% and above 10-fold ULN in 26.6%.
  • Deamidated gliadin IgA (DGL IgA) decreased in the vast majority but did not distinguish response of GFD from random fluctuations.
  • The authors note that symptoms improved in most on GFD, but short-term response could reflect “regression to the mean…for a considerable share” as symptoms improved in the non-GFD group as well.

In their discussion, the authors reference a large study (n=487) which showed mean normalization of TTG IgA of ~400 days; longer times were noted in those with type 1 diabetes and higher baseline values.

My take: This study, while showing that TTG IgA levels improve after 3 months of a GFD, helps solidify my opinion that in those who are improving, followup serology could be obtained later.  My practice is to have followup serology after 6 months of a GFD in the majority of patients.

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