Immunological analyses of Long-term Molecular and Cellular Responses to Hymenoptera Venom Immunotherapy Indolent Systemic Mastocytosis patients.

Hymenoptera venom allergy (HVA) is a immunoglobulin E (IgE) mediated reaction
to insect stings, which may be severe and cause potentially life-threatening
anaphylaxis. Venom immunotherapy (VIT) is highly effective in inducing
peripheral tolerance against venom allergens, and provides a reliable and
long-term clinical protection to future stings.

Some HVA patients suffer from underlying indolent systemic mastocytosis (ISM).
In ISM patients HVA reactions are generally more severe and VIT is less
effective. We hypothesize that the reduced effectiveness of VIT in ISM is
either caused by the lack of an immunological alteration or that an
immunological alteration does occur, but is insufficient due to the mast cell
abundance.

The primary objective is to assess the adaptive T cell response to VIT in HVA
patients with underlying ISM (ISM+) after treatment induction (at thirteen
weeks) and upon reaching maintenance dose, after seven months, in comparison to
the baseline condition at the start of treatment. Secondarily, this response
will be compared to that of HVA patients without underlying ISM (ISM-)
undergoing VIT.

Prospective cohort study, assessing the immunological T cell response to VIT of
ISM+ and ISM- patients. Patients will be recruited at the UMCG, where
peripheral blood mononuclear cells (PBMCs) will be isolated and cryopreserved.
T cell cultures and analysis will be performed at the Swiss Institute of
Allergy and Asthma Research (SIAF).

Participation in the study concerns the collection of three additional
peripheral blood mononuclear cells (PBMCs) samples compared to standard care,
at baseline, at thirteen weeks and at seven months of VIT treatment. No
additional questionnaires or other interventions are required.
ISM+ patients receive their VIT in the outpatient clinic of the UMCG due to
their increased risk of side-effects from VIT treatment. We will collect the
PBMC samples during these visits. Therefore, no additional hospital visits are
required for this patient group. ISM- patients receive VIT at the day-care in
the UMCG until 13 weeks, when maintenance dose is reached. Afterwards treatment
is continued at the general practioner. Study participation hence implies 1
additional hospital visits for these patients.