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Our Tests Gut Health Assessment

Celiac Disease

Description/Background Information

Celiac disease (CD), or gluten-sensitive enteropathy, is an autoimmune disorder characterized by chronic inflammation of the small-intestinal mucosa in response to ingested gluten (the storage protein of wheat, rye, and barley) in genetically predisposed individuals.1 In this condition, undigested gliadin peptides—the toxic component of gluten—leak through the intestinal barrier, where they are deamidated by tissue transglutaminase (tTG) to form deamidated gliadin peptides (DGP), triggering an inflammatory immune reaction in the process.

Gluten-induced injury to the intestinal lining reduces the absorptive surface area by eroding the finger-like projections called “villi” (villous atrophy), reducing the secretion of digestive enzymes and making CD one of the most common causes of chronic nutrient malabsorption.2

Celiac disease is one of the most prevalent autoimmune gastrointestinal (GI) diseases [1% of United States (US) and European populations], but diagnosis is often delayed or missed owing to variable or absent symptoms.1,3,4 In fact, estimates suggest that only 17% of US cases are currently diagnosed.5 However, early serologic diagnosis and dietary therapy can significantly improve quality of life and prevent severe, life-threatening complications.

Testing for Celiac Disease

Testing for CD is indicated for patients with symptoms, signs, or laboratory evidence of malabsorption (e.g., chronic diarrhea, steatorrhea, abdominal pain/bloating after eating, weight loss, and/or reduced fecal pancreatic elastase), especially those with a family history of CD.1,6 Celiac disease is also more common in patients with irritable bowel syndrome, elevated liver enzymes, anemia, and bone and skin diseases, than in the general population.1,7-9

For detection of CD, serologic testing for celiac-specific antibodies is recommended, with diagnosis confirmed by duodenal mucosal biopsies and response to a gluten-free diet.4,10 Celiac antibody tests are also used for monitoring response to treatment. At Salveo Diagnostics, semi-quantitative detection of serum antibodies to tTG and DGP is performed by enzyme-linked immunosorbent assay (ELISA) using native human tTG and DGP antigens.

  • Immunoglobulin A (IgA) anti-tTG antibody is the preferred single test for detection of CD in persons over the age of 2 years, with sensitivity and specificity ~95%.1,11
  • The inclusion of IgG anti-tTG and anti-DGP antibodies increases sensitivity for accurate detection in children younger than 2 years and other individuals who are IgA-deficient (2–3% of celiac disease patients12).1,13
  • The use of anti-DGP antibodies in combination with anti-tTg increases diagnostic accuracy and may rule out the need for biopsy in > 92% of cases. Anti-DGP can appear a year before anti-tTG and has also been described to occur in cases of nonceliac gluten sensitivity (NCGS), a less severe but common condition.16 Isolated anti-tTG can occur in other autoimmune disorders, infections, etc.17-20
  • Salveo Diagnostics tests for anti-tTG (IgA and IgG) and anti-DGP (IgA and IgG) to maximize sensitivity and specificity of CD diagnosis in all patients.

The ACG guidelines suggest that diagnostic testing should be done with patients on a gluten-containing diet; but, for monitoring purposes, patients are expected to adhere to a gluten-free diet.1

Clinical Utility & Indications

Both genetic and environmental factors play a role in celiac disease onset. Predisposing human leukocyte antigen (HLA) risk alleles (HLA-DQ2 or HLA-DQ8) are necessary, but not sufficient, for its development, while timing of gluten introduction into the diet and early infections (before 6 months of age) are also important.13,21 Celiac patients with malabsorption issues caused by mucosal damage or pancreatic insufficiency may be malnourished and deficient in certain vitamins and minerals.22

Celiac disease often occurs not only in patients with GI symptoms, but also in those with other common conditions (even without GI symptoms)2,4,9,22:

  • Iron-deficiency anemia
  • Other nutrient deficiencies (vitamins B12, B6, D, folate, and zinc)
  • Fatigue
  • Increased liver enzymes
  • Dermatitis herpetiformis
  • Osteopenia/osteoporosis
  • Arthritis
  • Dental enamel defects
  • Infertility
  • Peripheral neuropathy

Iron-deficiency anemia is found in 46% of patients with subclinical CD, in whom it indicates more severe villous atrophy.12,23 Celiac disease is also more prevalent in individuals who have autoimmune or certain genetic disorders1,4,9:

  • Type 1 diabetes
  • Autoimmune thyroid disease
  • Autoimmune liver disease
  • Crohn’s disease
  • Selective IgA deficiency
  • Down syndrome
  • Sjogren syndrome
  • Turner Syndrome

Family members of individuals with these conditions may be at increased risk for CD. Celiac disease that goes undetected and untreated confers increased risk for the development of autoimmune disorders, small bowel adenocarcinoma, enteropathy-associated T-cell lymphoma, other GI cancers, and non-Hodgkin’s lymphoma.24,25

Celiac Disease Antibodies Cut Points & Interpretation

Negative Weak Positive Positive
 <20 U 20-30 U >30 U

References

  1. Rubio-Tapia A, et al. Am J Gastroenterol 2013;108:656–676.
  2. Harris LA, et al. Gastrointest Endosc 2012;76(3):625–640.
  3. Wakim-Fleming J, et al. Clin Gastroenterol Hepatol 2013;11(5):511–516.
  4. Nadhem ON, et al. Postgrad Med 2015;127(3):259–265.
  5. Rubio-Tapia A, et al. Am J Gastroenterol 2012;107:1538–1544.
  6. Leeds JS, et al. Aliment Pharmacol Ther 2007;25(3):265–271.
  7. Sánchez-Vargas LA, et al. Neurogastroenterol Motil 2016;28:994–1000.
  8. Freeman HJ. World J Gastroenterol 2015;21(31):9233–9238.
  9. Kelly CP, et al. Gastroenterology 2015;148:1175–1186.
  10. Bai JC, et al. J Clin Gastroenterol 2013;47:121–126.
  11. Lewis NR, Scott BB. Aliment Pharmacol Ther 2010;31:73–81.
  12. Halfdanarson TR, et al. Blood 2007;109:412–421.
  13. Fasano A, et al. N Engl J Med 2012;367:2419–2426.
  14. Sugai E, et al. World J Gastroenterol 2010;16:3144–3152.
  15. Oyaert M, et al. Clin Chem Lab Med 2015;53(10):1537–1546.
  16. Fasano A, et al. Gastroenterology 2015;148:1195–1204.
  17. Vojdani A, Perlmutter D. Case Reports Immunol 2013;2013:248482.
  18. Vojdani A, et al. Eur J Inflamm 2008;6(1):1–10.
  19. Ferrera F, et al. Clin Exp Immunol 2009;159:217–223.
  20. Picarelli A, et al. Clin Chem 2003;49(12):2091–2094.
  21. Jill N, et al. JAMA 2005;293:2343–2351.
  22. Wierdsma NJ, et al. Nutrients 2013;5:3975–3992.
  23. Daya HA, et al. Clin Gastroenterol Hepatol 2013;11:1472–1477.
  24. Freeman HJ. World J Gastroenterol 2009;15:1581–1583.
  25. Grainge MJ, et al. Aliment Pharmacol Ther 2012;35:730–739.