New Serology for Celiac Disease?

A recent study (RS Choung et al. Gastroenterol 156: 582-91) showed that synthetic neoepitopes of the transglutaminase-deamidated gliadin complex are better noninvasive biomarkers for detecting celiac disease and for monitoring mucosal healing.

Link to Graphical Abstract and Abstract: Synthetic Neoepitopes of the Transglutaminase–Deamidated Gliadin Complex as Biomarkers for Diagnosing and Monitoring Celiac Disease

The authors studied the serum samples from 90 patients with Celiac disease (CD) and from 79 healthy controls and developed a fluorescent peptide microarray platform  Then, the authors validated their findings in 82 patients with newly diagnosed CD and 217 controls.

Key findings:

  • 7% of patients with treated (with gluten free diet [GFD]) and healed CD had positive TTG-IgA and 27% of patients treated but unhealed CD mucosa had positive TTG IgA
  • With the synthetic neoepitopes, CD was identified with 99% sensitivity and 100% specificity.  The assay identified patients with CD with healed mucosa with an 84% sensitivity and 95% specificity.

My take: More precise noninvasive markers like these should help identify individuals with celiac disease and those who have responded (or not) to the recommended gluten free diet.

Related blog posts:

Unrelated but important —NPR reports on another large study showing that MMR does not cause autism -Link: A Large Study Provides More Evidence That MMR Vaccines Don’t Cause Autism 

Related blog post: “Too many vaccines and autism” debunked

Link to full text of study from Annals of Internal Medicine: Measles, Mumps, Rubella Vaccination and AutismA Nationwide Cohort Study

Is a biopsy necessary in Celiac disease?

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).