AG&M annual report 2018

Hetty Bontkes and Maxine Rouvroye
AG&M Science Impressions 2018
diet) and autoimmune enteropathy have villous
atrophy of the small intestine in common. However
villous atrophy can only be determined by invasive
endoscopic procedures. We have shown that in these
cases the intestinal fatty acid binding protein (I-FABP)
is increased. Although I-FABP levels in serum have no
role in differential diagnosis of these three entities, the
levels do correlate with intestinal damage and as such
are a low invasive marker for intestinal damage.
In addition to the development of diagnostic tests,
we are currently investigating the functional role of
intraepithelial lymphocyte subsets and leucocyte
subsets residing in the lamina propria in the
development of these diseases in order to identify
possible future targets for therapy. Of particular interest
are the γδT-cells which increase in celiac disease and
remain elevated upon remission on a gluten free diet,
suggesting a protective role for these cells.
In 2017, Maxine Rouvroye started her PhD on diagnostic
approaches of (refractory) celiac disease and on the
epidemiology of gluten related neurological disorders.
The spectrum of gluten related disorders consists
of a wide array of clinical manifestations triggered
by dietary gluten. Whereas celiac disease is the
best known disorder, increasingly more reports on
neurological manifestations of gluten sensitivity,
such as gluten ataxia emerge. However, the
underlying neuropathological mechanism is yet to
be unraveled. A large part of Maxine’s PhD focusses
on the epidemiology of gluten related neurological
disorders. In collaboration with the Radboudumc ataxia
clinic, the Maastricht UMC small fibre neuropathy
clinic and the Utrecht UMC neurology clinic we will
study the incidence of gluten related antibodies in
patients with ataxia and neuropathy of unknown
aetiology. Transglutaminase 6 is a member of the
transglutaminase enzyme family which has been shown
to be predominantly expressed in the central nervous
system. We hypothesize that not Transglutaminase 2,
but Transglutaminase 6 is the main autoantigen in
gluten related neurological disorders.
Atrophy of a particular class of neurons located in the
cerebellum, the Purkinje cells, is associated with ataxia.
In a study on post-mortem material of patients with
neuro-celiac disease we observed a significant loss of
these Purkinje cells and an influx of CD8+ lymphocytes
in the cerebellum (unpublished data) indicating a T-cell
mediated response in the brain. Further research
on these cases will focus on the origin of these
lymphocytes and their target antigens.
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