An observational study of immuneregulatory mechanisms in Juvenile Dermatomyositis

Juvenile dermatomyositis (JDM) is a rare chronic inflammatory disease of
childhood, in which the immune system targets the microvasculature of the
skeletal muscle and skin, leading to myopathy and a typical skin rash. The
exact etiopathogenesis is unknown. In our previous studies we have shown the
regulation of the immune respons by regulatory T-cells (T-regs) in peripheral
blood is different in JDM compared to healthy controls. Furthermore it has been
shown that in the muscle of JDM patients, where the inflammation takes place,
the expression of heat shock proteins (HSP) is increased compared to muscle
biopsies of healthy controls. We want to investigate whether regulatory T cells
respond towards HSP in peripheral blood samples and the muscle tissue, in order
to establish whether heat shock proteins can be used to induce tolerance in
JDM. Also, we aim to establish whether T cell responses relate to clinical
disease activity to identify markers to predict disease activity.

to investigate the role of regulatory T cells in response to heat shock
proteins in muscle and peripheral blood of patients with juvenile
dermatomyositis. To identify patterns in T-cell responses and cytokineprofiles,
in relation with clinical disease activity .
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This is an observational study in all children with juvenile dermatomyositis
known in our clinic. Two groups of patients can be distinguished: newly
diagnosed patients (estimated at 3-5 new patients per year) and patients that
are in follow-up in our clinic (n=45).
In newly diagnosed patients a muscle biopsy is taken to confirm diagnosis. This
minimally invasive procedure, during which several samples are taken through a
biopsy needle, takes place under general anesthaesia, for which an intravenous
access is necessary. For this study we want to use the muscle biopsies, not
being used for diagnosis, and a peripheral blood sample taken during
anaesthesia prior to the start of therapy. Subsequently blood sampling will
take place at t=+3, t= +6, t=+12, t=+24, T= +36, t=+48, t=+ 60 months, to
evaluate the immunological factors during active disease, disease in remission
with and without medication. This bloodsampling will only be done in
combination with routine laboratory testing. JDM patients currently known in
our clinic will be followed for 5 years after diagnosis, and blood sampling
will take place at the same timepoints after diagnosis as mentioned before. The
control group consists of children referred to the pediatric neuromuscular
outpatient center *Spieren voor Spieren (S4S)*- for evaluation of muscle
weakness, that need a muscle biopsy to establish a diagnosis. In these children
muscle tissue and peripheral blood samples will only be at only one timepoint.

In most children with JDM muscle biopsies will be taken to confirm the
diagnosis. Because in JDM the inflammation in the muscle tissue is scattered,
routinely a minimum of three muscle needle biopsies will be taken, to ensure a
biopsy with sufficient inflammation for evaluation. For our study we want to
use the muscle biopsy samples, which are not used for diagnostic reasons. Blood
sampling will be combined with blood sampling for regular laboratory controls.
Subsequent sampling will take place in the outdoor patient visits, in
combination with routine laboratory testing. The amount of extra bloodsampling
(5-20 cc) will be adjusted to age and weight.