SubCutaneous Immunotherapy Treatment Effect (CITE) study

Allergen-specific immunotherapy (SIT) is the only causative treatment for
IgE-mediated allergy. Successful SIT has been associated with the induction of
allergen-specific *blocking* antibodies, regulatory T-cells and the shift from
allergen-specific Th2 towards Th0/1-like responses. However, it is still not
clear which of these immune mechanisms actually translate into clinical
tolerance to allergens and why SIT is not successful in a substantial fraction
of patients.

We seek to elucidate the immune mechanism(s) that are relevant for clinical
tolerance to inhalant and food allergens. For this purpose, patients suffering
from allergy to birch pollen and/or house dust mite who receive routine-SIT
will be assessed for the success of the treatment by employing nasal challenge
tests with the respective allergens. In birch pollen-allergic patients,
(changes in) tolerance and non-tolerance to birch pollen-related foods will be
evaluated by employing oral challenge tests with the major apple allergen Mal d
1. The composition, specificity and diversity of allergen-specific antibody and
T cell responses will be monitored in blood samples from the individuals
collected before and at different time points during SIT.

The study comprises two parts:
1. Department of Allergy, Rotterdam: Analysis of the clinical success of
routine allergy treatment using birch pollen (BP) and/or house dust mite (HM)
extract (3-5 years). The study will focus on the first two years of treatment,
thereby identifying patients responsive or non-responsive to SIT.
2. Medical University of Vienna: In vitro immunological analyses of
SIT-responders and non-responders.

Routine subcutaneous allergen specific immunotherapy with BP and/or HM extracts

Potential burden and risks are associated with those investigations not being
part of daily clinical care.
- Patients with BP allergy: Nasal challenge tests with BP extract before and
after 12 and 24 months of SIT (2 hours per visit). Nasal challenges may induce
upper airway symptoms: itching, sneezing, nasal discharge and blockage. Oral
challenge tests with apple and Mal d 1 before and after 12 and 24 months of SIT
(Mal d 1/placebo: 2 visits of 2 hours per visit, apple: 1 hour). The challenge
with Mal d 1 or apple may cause a so-called oral allergy syndrome: itching,
tingle or soreness of lips, mouth, throat, ears, sneezing. Systemic reactions
are not expected. Skin tests (20 minutes) and blood sampling are planned at 3
and 5 time-points respectively. In total 15 visits in 24 months are foreseen in
patients with concomitant apple allergy, in patients without apple allergy 6
visits are planned .
- Patients with HM allergy: Nasal challenge tests with HM extract before and
after 12 and 24 months of SIT (2,5 hours per visit). The nasal challenge may
induce upper airway symptoms: itching, sneezing, nasal discharge and blockage.
Skin tests (20 minutes) and blood sampling are planned at 3 and 5 time-points
respectively. In total 7 visits in 24 months are foreseen.
- If patients are undergoing treatment with both SIT BP and HM, they may take
part in both studies to BP and HM responsiveness. This is however not obligatory
Benefits for the patient: At an individual level patients will be better
informed about the degree of their individual allergies. In addition, they will
obtain an objective evaluation of the clinical success of SIT after 12 and 24
months. At a group level information the efficacy of SIT with BP on birch
pollinosis as well as on associated food allergy will be evaluated. Information
on the efficacy of SIT with HM will also be obtained. Moreover, insights on
immune mechanisms underlying the induction of clinical tolerance to allergens
will be obtained. Possibly, the study will identify biomarkers indicating
whether SIT is effective or not at an early time point of treatment.