Wednesday, July 2, 2014

Serological Tests for The Diagnosis of Celiac and Gluten Sensitivity- Critical Assessment of Utility.

For years I used biopsy and serology tests along with history, physical, elimination diet, diet challenge and lab assessment to make a diagnosis of gluten sensitivity.

I found serological tests,especially IgA tTG, frustrating because they never matched, in clinical practice, their often quoted and promised specificity and sensitivity of 0.98 (95% CI: 0.97, 0.99).

Except in rare circumstances I have abandoned serological testing for celiac and gluten sensitivity and I present two studies that show the tests are less than 60% accurate ( to state it in a general way). In fact, Ontario Health Insurance Plan pays for lab tests in practice, but, for Ontario residents it does not pay for serological tests for celiac and gluten sensitivity, and does not pay for IgA tTG. Have the decision makers at OHIP decided the serological tests are not strong enough utility to be included in the plan while they pay for small bowel biopsy? 

See the Health Quality Ontario report on utility of serological tests for the diagnosis of celiac disease:.

Clinical Utility of Serologic Testing for Celiac Disease in Ontario An Evidence-Based Analysis Health Quality Ontario Ont Health Technol Assess Ser. 2010; 10(21): 1–111.
Published online Dec 1, 2010.
Executive Summary

Objective of Analysis
The objective of this evidence-based evaluation is to assess the accuracy of serologic tests in the diagnosis of celiac disease in subjects with symptoms consistent with this disease. Furthermore the impact of these tests in the diagnostic pathway of the disease and decision making was also evaluated.

Celiac Disease
Celiac disease is an autoimmune disease that develops in genetically predisposed individuals. The immunological response is triggered by ingestion of gluten, a protein that is present in wheat, rye, and barley. The treatment consists of strict lifelong adherence to a gluten-free diet (GFD).

Patients with celiac disease may present with a myriad of symptoms such as diarrhea, abdominal pain, weight loss, iron deficiency anemia, dermatitis herpetiformis, among others.

Serologic Testing in the Diagnosis Celiac Disease
There are a number of serologic tests used in the diagnosis of celiac disease.
Anti-gliadin antibody (AGA)
Anti-endomysial antibody (EMA)
Anti-tissue transglutaminase antibody (tTG)
Anti-deamidated gliadin peptides antibodies (DGP)

Serologic tests are automated with the exception of the EMA test, which is more time-consuming and operator-dependent than the other tests. For each serologic test, both immunoglobulin A (IgA) or G (IgG) can be measured, however, IgA measurement is the standard antibody measured in celiac disease.

Diagnosis of Celiac Disease
According to celiac disease guidelines, the diagnosis of celiac disease is established by small bowel biopsy. Serologic tests are used to initially detect and to support the diagnosis of celiac disease. A small bowel biopsy is indicated in individuals with a positive serologic test. In some cases an endoscopy and small bowel biopsy may be required even with a negative serologic test. The diagnosis of celiac disease must be performed on a gluten-containing diet since the small intestine abnormalities and the serologic antibody levels may resolve or improve on a GFD.

Please take a good look at appendix 3 which summarizes 5 studies of serological tests. If you eliminate Zintzaras et al. (2006) (28) and Lewis et al. (2006) (26), the first listed studies, the ranges of sensitivity and specificity, especially of the most useful test IgA tTG are so much lower, than the first two. I don't see any explanation. And the review did not include Dr. Abrams et al , Dr. Peter Green's Celiac research lab's published study in 2006 which showed much lower sensitivity and sensitivity in field trials of IgA tTG.

Dr. Abrams and Green conclude

The sensitivity of the anti-tTG antibody in clinical practice is not as high as previously reported in research laboratories. The sensitivity is significantly lower in patients with partial villous atrophy. There is also significant variability in test characteristics among major commercial laboratories in the United States. These results need to be confirmed in prospective studies.

This is a partial answer to the question I proposed about the appendix 3 results; variation in condition of the villae needs to be taken into account. In an initial assessment for diagnosis, one would not know the condition of the villae and the treatment does not vary with mild disease or serious disease. Mild disease (with more chance to have a negative serological test) appears to be as dangerous as more severe villous atrophy. But starting the right diet ASAP is very important.  So I just want to know if the person is gluten sensitive and get them started on a GAPS diet and protocol.

In my opinion there is a major weakness of this Health Quality Ontario review as it was designed to only look at English language studies of the utility of serological tests. This is unfortunate as there is a wealth of information coming from the Italian, Japanese, Scandinavian, German and other non English, large celiac research centres.

Does anyone know if there is a "Celiac Research Centre" in Canada? Please let me know if you know of one.

To Your Health
Dr. Barbara