Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
 Home | Pathology Group MembersOur Hospital  Search This Website:
        Gliadin antibodies test, blood
      

It is important to diagnose celiac disease (CD) early because if the risk that it lead to intestinal lymphoma. And, there are other troublesome problems associated with the disease, in 2010 to even include increased instances of migraine & carpal tunnel syndrome in those with celiac disease. In the same review, it was noted that many CD patients experience psychiatric problems, with 35% of celiac patients reporting a history of depression, personality changes, or psychosis; and there are other neurological disorders such as ataxia14.

For at least a decade (since 1998), our GIs have screened for the sero-cellular autoimmune disease, celiac disease (CD) (gluten sensitive enteropathy [GSE]), with EGD plus distal duodenal biopsies (which we stain with IHC for CD3 in search of increased intraepithelial lymphocytes [IELs] expressed by the IHC amplified VTS...villous tip score)13. Unless there are increased IELs, the DISEASE STATE of GSE can't be present (even if constitutional, genetic...see below...basis exists in a given patient). Until someone proves us wrong, I (EBS) think the elevated VTS by biopsy is the most sensitive test for GSE and PSE (genetic screening checks for genetic predisposition & not for diseased condition). Positive biopsies are followed up with serological testing. When biopsy histology & VTS are normal, a protein sensitive enteropathy is HIGHLY unlikely. Unless the pathologist sees something concerning about the pattern of a borderline VTS, then the biopsy is interpreted as essentially normal.

A VERY confounding note is the comment about which we as pathologists can't be certain but should keep in mind, "If you do not have the commonly recognized genetic patterns associated with celiac disease you are generally excluded from the risk of ever getting the full autoimmune disease and don’t need to be periodically retested though you can be intolerant or sensitive to gluten11." That is, some folks are "gluten intolerant" (no autoimmune aspect) or have "wheat allergy" due to IgE effects.

For the first quarter of 2008, the biopsies signed out by one of us are as follows:

VTS normal @ 3 or less
VTS borderline @ 4-9
VTS elevated @ 10 or higher
9 cases
5 cases
2 cases:
(S08-2229, VTS 5-15 [no serology follow up in EMR ] & S08-4888, 15-18 [IgA competent & neg. EMA & tTG...probably some other type of PSE ])

In February 2008, we began in our lab (LML) to offer an IgA-patient-status-verified, 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 means refernece lab IgG negativity in an IgA incompetent patient (we have had elevted VTS, IgA incompetent, and abnormal IgG serology S11-1522). Seronegativity IN OUR LAB when the biopsy was highly suspicious or positive may indicate (1) some other PSE or enteropathy, or (2) GSE on a gluten-free diet 3 weeks or longer, or (3) refractory GSE, or (4) GSE with lymphoma.

The currently favored screening 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: The tests tend to be for IgA autoantibodies; so, negative tests are not trulynegative unless it is proven that the patient is IgA competent. If IgA incompetent, testing via IgG can help; or, a test for anti-deaminated gliadin peptide (DGP, by IgA and IgG). 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.

Genetic testing8:

Blood tests can only screen for RISK of celiac disease and cannot confirm whether a disease state actually exists. When blood tests and biopsy are inconclusive, testing for specific HLA (human leukocyte antigen) DQ2/DQ8 genes (located on the short arm of chromosome 612) associated with celiac disease may be helpful. As an autoimmune disease, CD is the result of the interaction between genes and the environment (gluten). All the necessary genes to develop CD are not known; however, HLA DQ2 and/or DQ8 are absolutely necessary to develop CD (and about a third of the USA population carries those genes). Since one-third of the population also have these genes, the presence of DQ2 or DQ8 does not imply that the person will develop CD, rather, that they have a genetic compatibility with CD. Genetic testing does not diagnose celiac disease – the absence of DQ2/DQ8 almost always rules it out...IF the test involves detection of both alpha & beta subunits (check with the lab). See details HERE .

Situations having undetectable antibodies:

  • celiacs who are tested about 3 weeks or more after going on a gluten-free diet (as one might do when told by the doctor of suspicion of their having CD & giving a prescription for the lab tests & patient oimmediately goes gluten-free but delays getting around to lab testing9.
  • celiacs with 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.
References:

  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, the March 2008 issue...(celiac serology review for LMC lab).
  8. Celiac Disease Foundation website.
  9. Celiac.com website.
  10. Family Practice Notebook section on celiac workup.
  11. Scott M. Lewey, "Update on Genetics of Celiac Disease", HERE. (also note his "The Food Doc" website HERE).
  12. Wikipedia celiac section, HERE.
  13. Editorial about celiac disease and under-detection in the USA, JAMA 302(11):1223, 16 Sept. 2009.
  14. Medscape Medical News, 7 Jan. 2010.
(posted 9 February 2002; latest addition 25 June 2011)
 
© Copyright 1999 - 2006, all rights reserved, Pathology Associates Of Lexington, P.A.