In February 2008, we began to offer an IgA patient status verified [the first pos. case S08-1663], biopsy correlated celiac serology profile (or any of the profile components, individually). Serological tests can provide confirmatory negativity or positivity in the form of a serological line of evidence and titered results allow one to test for dietary restriction compliance by a poorly responding patient. Seronegativity when the biopsy was highly suspicious or positive may indicate some other PSE or enteropathy.

The currently favored test⁶ is the anti-EMA test in an EIA/ELISA format called the tTG test which detects anti-endomysial  IgA Ab because that Ab (same as the IFA Ab ) has affinity for the tTG (tissue transglutaminase) enzyme, especially when it is complexed to gliadin as a test substrate (antibodies to gliadin-tTG complex). In the USA, the prevalence of these antibodies among Caucasian blood donors is 0.3-0.4%. Celiac disease (celiac sprue, gluten sensitive enteropathy [GSE]) has a USA prevelance between 0.5 & 1.0%; 3% of those with celiac diseas have IgA deficiency⁶. For the test to be effective, clinical sifting by symptoms, history, and other data are required to increase the prevelance of the diseas in the tested group...since performance in the general population of very low prevelance yields a positive predictive value (PPV) of only 49.7% but with a negative predictive value (NPV) of 99.9%⁶.

TEST review: A significant percentage of patients who have the diarrhea problems of celiac sprue have IgG and/or IgA (IgA is more specific & less sensitive than IgG) antibodies circulating in their blood. When the clinical suspicion for celiac disease is not very high, the presence of this "gliadin" antibody (A-gliadin, of the alpha gliadin fraction of ethanol soluble fraction of gluten, is the antigen for the test) or the anti-endomysial  antibody may serve as an additionally compelling indication for capsule or endoscopic (EGD) duodenal/small bowel biopsy to make or refute the diagnosis of celiac disease. Combined IgA and IgG tests are said to have the sensitivity of the anti-endomysial⁵ test. Many consider the anti-endomysial (EMA) test by IFA (perimysial fibers in monkey esophagus substrate) or by ELISA (tissue transglutaminase...tTG...test) to be much better than the anti-gliadin (which has more false positives).

The patient's system develops antibodies (Ab) against the gliadin component of gluten, gluten being found in wheat, oats, rye, and barley. Lymphocytes and plasma cells accumulate in the small intestinal mucosal lamina propria, and lymphocytes constantly spill through the surface epithelium into the intestinal lumen. In the process, they damage the absorptive cells which then fail to properly replace themselves, and nonsecretory crypt epithelium displaces more and more superficially. In time, the secretory cells become so scarce that the villi become flat to non-existent (though the actual mucosal thickness remains unchanged [villous...but not mucosal...atrophy]). These changes are typically worst proximally (this is why endoscopic duodenal biopsies are the preferred biopsy specimen), and with reversion to normal under treatment being slowest proximally. Can significantly revert toward normal in 4-6 weeks (LMC-01-1463?).

Anti-reticulin antibody was an original GSE-associated antibody, followed by anti-gliadin and then anti-EMA by IFA & then tTG.

Only 40% of biopsy-proven celiacs have classical symptoms (diarrhea, flatus, painful intestinal cramping and rumbling/gurgling...borborygmus), and many with symptoms are thought first to have irritable bowel syndrome (IBS). Chronic iron deficiency anemia without obvious cause is another presentation. Prevalence among USA Caucasians is about 1 in 150, with a 6% prevalence in juvenile-onset diabetics. Pregnant women with celiac disease have a 9-fold increased rate of spontaneous abortions and/or low birth weight infants and a 3-fold increase in IUGR. About 66% of persons with intensely itchy dermatitis herpetiformis have duodenal biopsy findings of celiac disease.

Situations having undetectable antibodies:

• small intestinal lymphoma
• refractory sprue (previous biopsy-proven celiac sprue but with failure to become well on a gluten-free diet)
• IgA-deficient individuals won't have the appropriate IgA Ab positivity (and yet have celiac disease at 10x the usual rate⁵)

Situations having detectible antibodies:

• celiac sprue (GSE) cases, active and untreated (S-01-2705)
• this antibody doesn't decrease/disappear as well with treatment as the anti-endomysial Ab and is not very good for checking on dietary compliance
• in cases suspected clinically of being GS enteropathy but subsequently disproven, the false positive rate is 20% (and most in this study were either Helicobacter pylori positive or had GERD type biopsy changes of esophagus)⁴
• other diseases (LMC-01-1463); and IgG false positive rate of 20% and IgA rate of 3%⁵

1. Sleisinger and Fordtran's: Gastrointestinal and Liver Diseases, 6th Ed., vol. 2, 1998.[LMC library]
2. Contemporary Issues in Surg. Path: vol. 2.....Pathology of the Colon, Small Intestine, and Anus; H. T. Norris, Editor; 1983. [EBS office]
3. James Goeken, MD, CAP Today, August 2000, page 66
4. Goldstein, NS and Underhill, J, Morphologic Features Suggestive of Gluten Sensitivity in Architecturally Normal Duodenal Biopsy Specimens,  AJCP 116(1):63-71, July 2001.
5. Bradwell AR, Atlas of Autoantibody Patterns on Tissues, 1997 [@ LML]
6. Presutti RJ, et. al. of Mayo Jacksonville, "Celiac Disease", American Family Physician 76(7):1795-1802, 12/15/07.
7. Carter JB, NewsPath, March 2008 (celiac serology review).