Frequently Asked Questions Find everything you need to know about coeliac disease, the gluten free diet and the work we do.
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Is it considered normal for ttg levels to drop dramatically in one year, or is this considered an erroneous result? (I.e. On the scale where 10> is positive, dropping from a ttg level in the 100s down to <4 in one year)
Yes, such a drop can often be seen when the patient is fully compliant with a gluten free diet.
How common is thrombocytopenia in coeliac disease and how should it be managed?
I think it is quite infrequent. But some patients have several immune disorders at the same time, unfortunately.
Question to Ludvig Sollid – why did you choose to research coeliac disease and stay interested in it?
By chance as many other things in life.
I was a medical student and wanted to do research. In the medical school curriculum, cellular immunology had fascinated me. I thus contacted immunology professor Per Brandtzaeg to ask whether there was an option to take a gap year and get involved in research. Per had just supervised a doctor (Helge Scott) together with another immunology professor Erik Thorsby. The PhD thesis of Helge was on the topic of immunology of coeliac disease. Per and Erik suggested I should follow the paths of Helge as this would also include studies of T cells. I thought this was a good suggestion and started.
After several backlashes and a feeling of being completely useless, I made progress. I took another leave from medical school and during this period I made the discovery of HLA-DQ2 being a culprit molecule in coeliac disease. I was utterly fascinated and absorbed by science and after medical school and completing service to become a licensed doctor, I went back to the lab. I have more or less worked there since.
Why does the body have transglutaminase, can you live without it – get rid of it? If so, would this cure Coeliac Disease?
Transglutaminase 2 (TG2) is a wound healing enzyme, and its natural role is to crosslink proteins in the body. We cannot remove TG2 but we can inhibit the enzymatic activity of TG2. This would prevent TG2 from modifying gluten peptides in the gut. Because the T cells that respond to gluten in coeliac disease depend on this modification, we think that inhibition of TG2 activity should prevent the activation of gluten specific T cells.
A drug that does exactly that, a TG2 inhibitor, is currently tested in patients with coeliac disease (clinical trial by Dr. Falk Pharma). This is a good example of observations from the clinic (antibodies to TG2, and gluten specific T cells from gut biopsies) that were studied in the lab and where the discovered mechanisms have led to development of therapy.
Will Jorunn’s research looking at the proteins be able to tell you if someone has coeliac disease or refractory coeliac disease?
Not yet, but we hope that such distinctions can be made in the future.
At the moment it is not clear whether refractory coeliac disease (RCD) type I is mechanistically similar to or different from untreated coleiac disease, even though we know that RCD I patients have little or no effect of a gluten free diet. We have not yet studied RCD samples by our protein analysis approach, but we plan to do so in near future.
Is there currently any research into Refractory coeliac disease I and II? Just been diagnosed with refractory 1 and it seems very little is known about it?
Yes, there is research on both, in particular refractory coeliac disease II with malignant cells.
Basic science studies and a very few drug trials have been done or are ongoing. refractory coeliac disease I is tricky. It is for sure a mixed bag where inadvertent, continuous gluten exposure is a frequent cause.
In many other cases, the patient is clinically well, but the gut takes a long time to heal.
How close are we to understanding what causes coeliac disease, particularly why some people with the genes do not go on to develop it? And how helpful is this line of research to us? Will it lead to developing preventative measures?
Our current understanding of the disease mechanism in coeliac disease is way better than for other immune mediated diseases like type 1 diabetes or rheumatoid arthritis. Yet, there is still a lot we do not understand. For instance, as you mention, why not everybody who carries the genes for HLA-DQ2 or HLA-DQ8 does not develop the disease. We know that genes other than the HLA genes are implicated in the development of coeliac disease.
Many people who carry the HLA-DQ2/DQ8 do not develop coeliac disease and so it’s most likely they lack some of these other non-HLA susceptibility genes. In addition, we strongly believe that environmental factors other than gluten, for instance diarrheal viruses, are involved in coeliac disease development.
Some HLA-DQ2/DQ8 carriers who do not develop coeliac disease may have avoided a critical viral infection.
There is much to learn. The ultimate goal, and what hopefully can be achieved with even better insight, is prevention of coeliac disease.
How successful was the Celimmune trial for refractory coeliac disease? What did it involve?
The study was published last year.
The primary endpoint was not met, unfortunately, but some effect was seen. Some patients benefitted from the treatment, but their problems were not solved overall. The drug may be developed further, but many of us were a bit disappointed by the result.
Why do the T cells respond to gluten in wheat, barley and rye? Why do some respond to the gluten in oats?
The short answer is that we believe it is more difficult to make immune (T-cell) responses to gluten proteins of oats than to gluten proteins of the other cereals.
Coeliacs have T cells responding to certain peptides (what immunologists call epitopes) of wheat, barley and rye. (BTW: all peptides have to be modified by transglutaminase 2 in the body before T cells will recognise them). Some epitopes are shared between different grain types, some are specific for a certain type of grain. What initiates the response to a given epitope and the expansion of specific T cell clones that follows, we believe is related to how much of an epitope will survive gut digestion. After an initial sensitisation to an epitope, the immune system becomes very sensitive to this epitope requiring very little to get fired up. The epitopes of oats that some very few coeliacs mount responses to, are part of cereal proteins that are not very resistant to digestion by the gut digestive enzymes. This is in contrast to most other gluten epitopes of wheat, barley and rye. Thus, it is less of a chance to get sensitised to oats.