Discussion Points…

(1) I understand that the new test you have helped to develop is called the Tissue Transglutaminase Test. Can you give me an explanation of how it works (using terms laypeople would understand)?

Gluten, the protein in our daily food wheat, rye and barley, induces a disease called coeliac disease in certain susceptible individuals. The true prevalence of the disease seems to be as high as 1:100 in healthy individuals and undetected coeliac disease is very common with between 5 and 10 (in some countries up to 100) cases going undetected for every person diagnosed by routine clinical methods within health care systems. All such undetected cases will continue to ingest gluten and will have manifest small-bowel mucosal injury. Ingested gluten induces antibodies against the patients own tissue material and these antibodies we may detect in the blood (serum).  This highly sensitive and specific serologic screening test has already been available for years and one may detect even clinically silent coeliac disease with the test. That test is called the endomysial antibody test. 

Sero-positivity for these autoantibodies is held to be pathognomonic for untreated coeliac disease. However, this test is subjective, being observer and laboratory dependent, but it works well in experienced reference laboratories. Very recently it was identified that the human tissue structure against which these antibodies are targeted, is tissue transglutaminase.  Based on this invention, we introduced a serological test, observer non-dependent and easy to perform where antibodies against tissue transglutaminase is detected. The industry has already developed simple kit-tests suitable for screening even large populations. The ultimate diagnosis of coeliac disease is established by small-bowel biopsy, and is usually carried out by upper gastrointestinal endoscopy. This procedure is inconvenient to most individuals. Therefore, to minimize the need of biopsies a reliable screening test, which is both sensitive and specific, is of uppermost importance. Routine application of such a test would enable appropriate selection of subjects for biopsy and final diagnosis.

(2) How accurate is this test compared with other blood tests for celiac disease? Why is it more accurate?

See above. The tissue autoantibody tests are accurate but need specific technique, works well in experienced labs. this new test is based on ELISA, and kits have already been developed, some 15 on the market today. May be performed in most places. As it is now, they are 95% sensitive and 95% specific for untreated coeliac disease. Second generation kits are on their way.

(3) Who did you work with to develop this test?

There was a race for years to name the structure in human tissue that was responsible for what we called reticulin and endomysial antibodies. We were very near, but Detlef Schuppan and his group got the name. In my group we then developed an serum antibody test against tissue transglutaminase (I will give some references at the end).

(4) How has it been tested?

…since 1998 there are many published papers on the subject.

(5) How much will the test cost?

We charge US $15 for an in-house test, and in routine we changed to a commercial FDA-approved kit, and the cost is the same for the patient.  My research lab performs some 12,000 serological test for coeliac disease per year.

(6) When will it be available in Canada and the U.S.?

I think it is available already. Inova Diagnostics Inc, San Diego, has on the market one FDA-approved kit.

(7) Dr. Issenman tells me that your research indicates that celiac disease is 10 times more common than we previously thought -- 1:240 to 1:400 ... Is that correct? Why do you think it is that common?

See above, 1:100 might be the true prevalence.  Doctors read the textbooks, the disease does not. Clinically we have seen a changing pattern of disease features. Extraintestinal manifestations are more common than cases with GI symptoms. One most common incorrect diagnosis in patients with different abdomional discomfort is lactose intolerance. this may be due to underlying gluten-triggered mucosal injury, coeliac disease.

8) Please tell me about the links between celiac disease and other  diseases ...

Too much for now, I could write for hours…

I will give some references below, try to find our review article in the Lancet from 1997. I will also attach my group published papers on coeliac disease. We have touched quite many aspects in the field.

(9) Does this mean that people who have these diseases or conditions should be tested for celiac disease?

Not all of them you mentioned, not Crohn's disease and diverticulosis, others yes (if you want to get indication for a gluten-triggered disease and to select patients for small bowel biopsy).

If they have it and they adopt a celiac diet, would their condition improve substantially?

Yes, it seems even so that clinically silent cases, healthy family members to coelaic disease patients who have a undetected disease seem to, benefit from treatment.  Quality of life improves (unpublished), bone density improves (our Lancet paper 1999), etc…

Why wait for complications on a long run if wheat ingestion has destroyed the intestinal mucosa, that is responsible for nutrient intake?  On a gluten-free diet on a long run there is no overrepresentation of disease entities, malignancies or mortality over the population in general.  But the prevalence of 1:100, even if one coming from many countries, is still a hypothesis as we face the fact of small populations that have been screened and large confidence intervals.  A prevalence of 1% will raise important issues for the future. First, the benefit of the treatment of clinically silent coeliac disease should be thoroughly investigated. The scientific community might come to an understanding that malignancies, osteopenia and osteoporosis (i.e. fractures), or even autoimmune diseases may be prevented by early detection and dietary treatment of coeliac disease. If so, screening policies would be easily generally agreed and accepted both by authorities and patients.  Secondly, we need future cost-effectiveness studies.

(10) Can you refer me to any journals where you have published your research results?

Within this email body I will list some. If you want to look what we have altogether published on this issue, please double click my home page http://www.uta.fi/~llmama/, the lists are there. Also if you click for Coelaic Disease Study Group, you will find some text on my group and a list of 20 papers, perhaps not the same as I list here.  I chose clinical papers and review articles. The titles tell something, and some journals you easily find in the hospital library.

Selected publications from my group
(I chose clinical, not basic research, not genetics, for more, please see my home page).

(Then there are interesting new data from other groups on neurological sequaleae, gluten ataxia, more on autoimmune diseases, etc…)

Penny 2000