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Moderated discussion and help for gluten free, coeliac, celiac, wheat allergies or intoleranceactioning query
| Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by Peter
|
The largest investigation into the prevalence of undiagnosed celiac condition in the general population is taking place in Europe with 4 million euros of EC funding.
So far over 18000 blood samples have been tested and the results suggest that 1 in every 80 people may show some adverse reaction to gluten, and so benefit from a gluten-free diet.
This figure is very much greater than the number at present medically diagnosed, so there are a lot of people out there suffering unnecessarily from the effects of gluten in their diet.
Coeliac EU Cluster Scientific Programme.
Peter
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
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Do you have any more details of the study - where did you find the information. I couldn't find any results. Thanks
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
|
I would like to see the study also. How did they decide there was a gluten reaction? What tests were given?
Kit Kellison
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
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|
could you please send link to this study as I wish to mail this to some Doctors in my area..Thanks, Donna
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
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|
I'd like to find the study also. Thanks so much for the information
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
|
May I request the same verification. I would also suggest that you forward the information to a physician of my aquaintance who is currently establishing a Celiac treatment center at the Mayo Clinic: schaffner.john@mayo.edu
Thanks
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
|
|
Do you have any more details of the study - where did you find the information? I would like to obtain a publication of the actual study. Can you provide a link or source? Thank you so much
| Post a reply to this message, or post a new topic | |
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by Peter
|
The Coeliac EU Cluster Scientific Program started in January 2000 with 4million euros of funding.
http://216.239.37.100/search?q=cache:R6XhAZMY1aEC:cdeuepid.uta.fi/CoeliacWeb/cluster\%2520\%2520Annual\%2520report\%2520Y2001.doc+EU+Cluster+Scientific+Program+celiac+coeliac&hl=en&ie=UTF-8
The link above is the html version of the report via google
cdeuepid.uta.fi/CoeliacWeb/ cluster\%20\%20Annual\%20report\%20Y2001.doc
Peter
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
|
|
These links are not working for me ... could someone send me a link that works to tara.rosenbohm@enron.com
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by Peter
|
br />
Try this link to the whole cluster project:
http://www.technapoli.it/eucluster/eucluster.htm
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
|
I tried the web site technapoli etc. but it was in Italian and I was unable to get the research article. How can I get a copy of the research. I have Celiac Disease and recovered from RA, Sjogren's and Lupus after accidental diagnosis. I also have both of the main genes for Celiac. I need information to try to get data to present to my grandchildren's doctor as they both show show signs of the diease and my daughter is totally resistant to having them tested. They are eight and thirteen years old. Could you tell me the major sites for research in the European Journals on Celiac.
Also do you know of any medical journals linking pancreatic disease and celiac?
Thank you so much for your help. My fax number is 310-393-3400 and my phone is 310-393-1353 should you wish to contact me. Again, Thank you. Marlene
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by Peter
|
br />
COELIAC-EU/CLUSTER N° QLK1-1999-00037
Year 2001 Annual report
By Bruno Jarry, Coordinator
Introduction:
Coeliac Disease (CD) is an autoimmune disorder triggered by the cereal protein gluten present in grain from wheat, barley, rye and their hybrids. Recent recognition of the socio-economical importance of the disease in Europe and in other parts of the world has led to the raising concern by the patients associations, the ediction of food safety related regulatory actions by Codex Alimentarius and Governments and concurrently to the implication of the food industry, especially the gluten producing industry, in facts finding and support to the academic research in the field. All this conducted to the organization of a large scientific program, funded for its largest extent by the EU Commission as part of the Quality of Life and Management of the Living Resources action in the 5th R&D Frame Work Program. The program, which brings together 16 laboratories from 9 Member States is organized as a cluster and is managed by AAC, the European Starch Manufacturers Association . It is funded under the "Food, nutrition and health" Key Action N°1 and will run for 3 years , starting January 1st, 2000.
Three topics are studied in this "cluster" type consortium:
(1) The prevalence of CD in Europe from a large epidemiological study associating the results from 4 member States ( Finland, Ireland, Germany and Italy).
(2) The genetic components associated with predisposition of the disease in the Nordic (Sweden, Finland, Norway), French, Italian and British populations.
(3) The physio-pathological mechanisms underlying the disease, at the cellular and molecular levels.
This report summarizes the achievements of this cluster during its second year. It is based on the individual reports of the three projects. The second annual review meeting attended by representatives from all the fifteen research teams was hosted by the University Federico II in Naples (Italy) on January 19th.
The Prevalence of Coeliac Disease
Under the acronym EPIDEMIOLOGY, this first project is aimed to conclusively determine the prevalence of CD in Europe. It is based on the well-documented finding that untreated CD patients specifically exhibit an increase in the serum titer of specific IgA antibodies called endomysial antibodies (EMA). These autoantibodies are directed against tissue transglutaminase (tTG), an enzyme known to be directly involved in the pathogenesis of the disease. Previous work had shown that the elevated level of EMA is limited to people exhibiting the genetic background required for expression of the disease. However many of these people do not express obvious clinical symptoms. The project aim is to create a simple noninvasive antibody kit test for measuring anti-tTG substituting the cumbersome EMA test. The scientific hypothesis is that people having an elevated titer of anti-tTG in their blood exhibit a gluten-induced disease and a small-bowel mucosal lesion, irrespective of their clinical status.
In order to reach this conclusion, the project is (a) testing on a large sample of population from 4 different Member States their developed anti-tTG kit test, based on purified human tTG produced by genetic engineering; (b) monitoring the level of anti-tTG IgA antibodies in 35.000 sera randomly collected in Finland, Germany, Ireland and Italy in order to detect people with seropositivity, and (c) testing biopsies taken from those people for abnormal mucosal appearance. It is expected that the monitoring of this large sample will allow for statistic evaluation of the hypothesis.
Progress report in December 2001 is the following:
1. 9133 sera have been collected in existing collections in Ireland and Germany
2. 16088 new sera have been collected from adults in Italy, Finland and Germany and 4978 from children in Ireland and Italy.
3. Parameters for use of a first generation kit test based on guinea pig tTG antigen has been validated against the EMA test and via a ring test on a small number of sera collected from identified coeliac patients and control individuals through the participating laboratories. This guinea pig derived antigen based kit has been launched on the market at the beginning of the project.
4. Same experiments have been performed by comparing the efficiency of the developed human antigen based test with the EMA test and the guinea pig antigen based test. At a cut-off of 7.0 the sensitivity and specificity of the human tTG based test is improved over the guinea pig tTG based test and results are more in concordance with the EMA test. The human tTG based test is far more reproducible and easy to use than the observer-dependent EMA test. The kit has been launched in the market under the trade name of Eu-tTG IgA umana in March 2001. At the same time, the kit was also submitted for FDA approval in USA which was granted in April 2001. Sales of the new kit in United States have already started.
5. Serum tTG antibody testing is still going on: 30,699 sera are already in the testing laboratory.
18,021 sera have been tested, allowing for the detection of 223 seropositive people with the human tTG based test kit. Altogether 106 sera in those 223 were also positive in the EMA test.
6. All the data are collected on the htpp://cdeuepid.uta.fi web site created and run by the Finnish partner in University of Tampere.
7. The patent covering the use of tissue transglutaminase in the diagnosis of Coeliac Disease was granted in the course of year 2001 in Australia, New Zealand, Europe, as well as in the USA.
8. The diagnoses via biopsy of the detected seropositive people will be done during the last year of the project according to a single protocol agreed by all the participants.
9. Two scientific articles are published and one is in press.
Genetics
Under the acronym GENETICS, this second project aims to investigate the genetic basis of gluten-induced disease in the European population as represented by Nordic counties ( Norway, Finland and Sweden), France, Italy and United Kingdom. It also searches for the genetic factors which modulate the abnormal immuno-response to gluten and its multivariate clinical expression ( susceptibility genes).
Progress report for year 2001 is as follows:
1. DNA samples from 647 families with one affected person have been collected as well as 525 DNA samples from duplex families. All the data are collected on a single web site ( htpp://techapoli.it/eucluster/eucluster.htm) run by the University of Naples.
2. 1634 patients originating from 1082 different families have been tested for their HLA-DQ2 status: the results show that DQ2 positivity is by far the largest case ( between 85 and 95 \% with slight variations between the countries). In that same sample 82 people were tested positive for DQ8 ( between 4 and 6\% depending on the country) and 27 people were neither DQ2 nor DQ8 positive.
3. The families corresponding to these 27 patients were used in a search for novel HLA-linked but non DQ susceptibility loci for coeliac disease by genetic mapping of the entire HLA gene region using microsatellite and other genetic markers in the selected families. At this stage the results differ from one population to another one and general conclusion is not possible.
4. Identification of genetic regions carrying potential susceptibility genes has been carried out using the individual sample collections collected in each country. Regions 5q, 11qter, and CTLA4/CD28 have been explored using microsatellite markers. So far individual results from the different groups differ and no general conclusion may be drawn.
5. Using a newly developed statistical model known as meta-analysis, an analysis of the individual genome screens performed by the different partners has been performed. It highlighted possible susceptibility regions in 5q, 11q, 2q and 14q besides the proven HLA region at 6q. This work will be further refined during the last part of the project.
6. 14 articles have been written and accepted for publications in peer review scientific journals.
Pathogenesis
The third project, acronym PATHOGENESIS, is focused on the biochemical, cellular and molecular events underlying the complex events taking place in the gut of the coeliac patients when challenged with gluten.
Results for this second year are as follows:
1. The cytokine messenger RNA pattern in biopsies from untreated and treated CD patients challenged in vitro with gliadin is dominated by Interferon-gamma. Interleukine-2 seems to play a role only in the early response to gluten challenge. The higher level of IL-10 observed in active CD probably down regulates the Th1 response. IL-15 and IL-18 are playing a role in the early phase of the gluten response and could act as drivers of the Th1 immunological response.
2. Human gut derived epithelial cell lines are sensitive to gluten challenge in vitro. Induction of epithelial cells death through apoptosis can also be observed in the biopsy cultures of treated patients upon gliadin challenge. It is a key factor in the pathogenic process leading to mucosal damage.
3. Preliminary micro-arrays experiments have been performed using gluten treated and untreated tissues in an attempt to identify the genes involved in the gluten response. Results so far are complex and experimental conditions require great attention to minimize artefacts.
4. Results have been reported suggesting that CD specific IgA antibodies do have an important role in the pathogenesis. They interfere with mesenchymal cell biological performance and could therefore also influence the epithelial cells resulting in disturbed epithelial cell behavior eg. increased proliferation and decreased differentiation.
5. The first evidence for a mechanistic link between the T cell response to gluten in the untreated celiac mucosa and the crypt hyperplasia so characteristic of this disease was brought when the distribution of the KGF transcripts within the tissue in the subepithelial layer was observed.
6. Genes regulated in TGFb-induced epithelial cell differentiation have been isolated and studied. From sequence comparison with already described genes of known function, it is suggested that one could be a transcription factor involved in the apoptotic effect. Anther has substantial similarity with a glycosyltransferase gene. This activity play an important role in invertebrate and vertebrate development.
7. New antigenic epitopes generated by the reaction of human and guinea pig tissue transglutaminase with particular gliadins have been generated. T cells clones have been established from intestinal biopsies and peripheral blood of patients and controls.
8. 9 scientific articles have been written. 7 are published or in press; 2 submitted.
Coordination and Dissemination of knowledge
The Cluster Coordination committee which brings together the leaders of the three projects and the Coordinator of the Cluster has met three times during the period, as well as each of the Project Coordinating Committees.
The Coordinator has been invited to make presentations on the Cluster at different occasions: in the EU-Commission, in industrial forums and in meetings bringing together the representatives of the Coeliac patients associations and industry representatives.
The second Annual review meeting was hold in Naples on January 19th, 2002 at the invitation of the Coordinator. The meeting was hosted by the Federico II University in Naples (Italy). Representatives of the Starch industry and of the Coeliac patients Associations attended the meeting together with the scientific teams members. A delegation of the African Mediterranean countries involved in Coeliac research also attended that meeting.
This report will be made available to all interested parties and will be put on the cluster web sites.
Bruno Jarry
Coordinator of the EU-coeliac research cluster.
Here you can find the joint publication and published results of the project.
List of Publications
Fabiani E, Catassi C and the International Study Group on Eu-tTG; The serum IgA
class anti-tissue transglutaminase antibodies in the diagnosis and follow-up of
coeliac disease. Results of an international study, European Journal of
Gastroenterology and Hepatology, 2000.
Korponay-Szabo I, Sulkanen S, Halttunen T, Maurano F, Rossi M, Mazzarella G,
Laurila K, Troncone R, Mäki M. Tissue transglutaminase is the target in both rodent
and primate tissues for celiac disease-specific autoantibodies. J Pediatr
Gastroenterol Nutr 2000;31:520-7.
Mustalahti K., Sulkanen S., Holopainen P., Laurila K., Collin P., Partanen J., Mäki M.
Coeliac Disease among Healthy Members of Multiple Case Coeliac Disease Families.
Scandinavian Journal of Gastroenterology 2002; 37: 161-165.
Mustalahti K., Lohiniemi S., Collin P., Vuolteenaho N., Laippala P., Mäki M.
Gluten-Free Diet and Quality of Life in Patients with Screen-Detected Celiac Disease.
Effective Clinical Practice 2002; 3: 105-113.
Abstracts
Fabiani E, Rondina C, Peruzzi E, Galeazzi R, Catassi C. J Pediatr Gastroenterol Nutr
200; 32: 355. The abstract was accepted as a poster at the ESPGHAN Meeting in
Geneve on May 9-2, 2001 and was presented orally as well.
Fabiani E, Rondina C, Peruzzi E, Galeazzi R, Garbuglia G, Bearzi I, Coppa GV, Catassi
C. Anti-guinea pig vs anti-human IgA tissue transglutaminase (tTG) antibodies as
screening test for coeliac disease (CD). The abstract was presented as a poster at
the 9th United European Gastroenterology Week in Amsterdam on October 6-10,
2001.
Fabiani E, Rondina C, Peruzzi E, Galeazzi R, Catassi C. Dig Liv Dis 2001; 33: 628. IgA
anti-guinea pig vs anti-human tissue transglutaminase as first-level screening tool
for coeliac disease. The abstract was presented as a poster at the 9th Meeting of the
Italian Society of Pediatric Gastroenterology and Epatology (SIGEP) in Pisa on
October 25-27, 2001
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by
|
you could always lookon the websites below
www.coeliac.co.uk
www.medinfo.co.uk
www.coeliac.org.au/diet.htm
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| Re Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by Arline Chambers
|
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Simple question - what is the range of test scores fo Ttg? What is the "normal" range for Ttg? I have a number "88". What does it really mean? Many thanks.
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| Re Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by Mari
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do you have to do a gluten challenge before having the Anti-Tissue Transglutaminase (tTG) IgA test?
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| Re Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by Peter
|
The following paper highlights the need for a gluten challenge. Note the results for group 2 - children on a gluten-free diet, compared with the results for group 3 - children on a gluten challenge. This very sensitive test detected less than half of known celiacs on a gluten-free diet without a challenge.
Peter
Title Radioimmunoassay to detect antitransglutaminase autoantibodies is the most sensitive and specific screening method for celiac disease.
Source Am J Gastroenterol (The American journal of gastroenterology.) 2001 May; 96(5) 1536-40
Additional Info United States
Standard No ISSN 0002-9270; NLM Unique Journal Identifier 0421030
Language English
Abstract OBJECTIVE The aim of this study was to establish the most sensitive and specific screening method for celiac disease. We tested three methods based on different principles, which all detect autoantibodies against the same antigen (tissue transglutaminase). METHODS Sixty-two celiac children at the first biopsy (group 1), 78 celiac children on a gluten-free diet (group 2), 14 celiac children on a gluten-challenge (group 3), and 56 controls with a normal duodenal mucosa (group 4) were studied. The methods used were 1) radioimmunoprecipitation assay using recombinant tissue transglutaminase (RIA); 2) commercial enzyme immunoassay using guinea pig tissue transglutaminase (ELISA); and 3) indirect immunofluorescence method for detection of antiendomysium antibodies (IF-EMA). RESULTS RIA antitransglutaminase autoantibodies were detected in 100\% of group 1, 43.6\% of group 2, 100\% of group 3, and none of the control subjects. ELISA antitransglutaminase autoantibodies were detected in 90.3\% of group 1, 9\% of group 2, 78.6\% of group 3, and in none of the control subjects. IF-EMA were detected in 95.2\% of group 1, 11.5\% of group 2, 92.3\% of group 3, and 1.8\% of the controls. CONCLUSIONS Our results demonstrate a very high sensitivity and specificity of the RIA method to detect antitransglutaminase autoantibodies in comparison to ELISA and IF-EMA assays. We can explain this finding with the use of human recombinant antigen and the increased capacity of the RIA method to detect low titers of autoantibodies. If our data are confirmed by studies on larger series, tissue transglutaminase RIA could be proposed as the best screening method for celiac patients.
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| Re: Anti-tTG blood test shows 1 in 80 celiac in population
| Posted by mobo
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If after blood tests one is allergic to cows milk, gluten, egg white, wheat, buck wheat, rice, rye flour and yeast, is one consider to be a celiac
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