The future of coeliac disease: immunology, environment and possibilities for new treatments.

As coeliac disease (CD) is a disease that is exclusively found in humans, the
continuation of basic and translational research lines depends on the ongoing
availability of patient derived materials from patients with and without CD.
Such material can be obtained through routine diagnostic procedures, like
venous blood sampling and the sampling of intestinal biopsies during diagnostic
endoscopy under general anesthesia.
Recent results and technological developments offer novel opportunities to
improve diagnostics and develop novel therapeutic approaches. For example, it
has become clear that in patients with CD a biased T cell receptor repertoire
is present that mediates the deleterious immune response to the dietary gluten
proteins. The availability of novel tetramer reagents now allows a direct
monitoring of the presence, abundance and functional characteristics of these T
cells in peripheral blood and biopsy material of patients. This enables studies
to determine if the occurrence of such cells coincides with disease onset
and/or severity of associated symptoms. Moreover, we have novel insight into
changes in the intraepithelial lymphocyte compartment that are associated with
CD. We also have evidence that there is cytokine mediated crosstalk between the
immune response in the lamina propria and epithelium which likely contributes
to pathology. Therefore we wish to further characterize these interactions in
functional terms in order to gain better insight into the involvement of innate
immunity in CD pathology. These studies are further facilitated by the
acquirement of the CyTOF mass cytometer, a new technological breakthrough
allowing the simultaneous analysis of up to 34 cellular markers on a single
cellular sample.
Ultimately we anticipate that these studies will be used to develop novel
strategies to prevent or treat CD by elimination of disease causing cells by
highly specific intervention targeting disease relevant cells without affecting
immunity in general.

The primary objective of CDfuture is to provide duodenal biopsies of patients
with and without CD, and venous blood samples, to continue CD research as
described above.

Case-control study

The extra biopsies and blood samples will be taken under general anesthesia
during diagnostic endoscopy for medical reasons unrelated to this research
protocol. This medical procedure in itself can cause stress and be a burden to
the patient. The relevant medical and nursing protocols that are used in the
LUMC describe among others guidelines to decrease stress, and increase safety.
However, the extra biopsies and blood samples that are taken for the research
described in this protocol cause no extra stress or burden since these
materials will be sampled under general anesthesia.
There is a limited risk to taking biopsies during endoscopy to develop
intra-intestinal or intramural hemorrhage, or even perforation. The risk is
estimated to be < 1:10000. There is no additional risk in sampling an extra 10
ml of blood.
CD develops at a very young age. Most children that are diagnosed with CD in
The Netherlands are below the age of 12 years. Therefore, in order to obtain
enough biopsies for the research described in this protocol, it is necessary to
include minors < 12 years of age in this study.