Regulatory Lymphocytes in Patients Treated With Specific Immunotherapy
Condition: Immunotherapy; Seasonal Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether specific subcutaneous immunotherapy affects
      fractions of regulatory T lymphocytes and histamine H2 receptor expression and ZAP70 in
      regulatory T lymphocytes.
    

Detailed description: 
      Allergy constitutes an important problem worldwide thus effective treatment is crucial for
      the reduction of symptoms severity, patients' activity and quality of life as well as for the
      reduction of direct and indirect costs of the disease. Specific allergen immunotherapy (SIT)
      is a potentially curative and specific method of treatment for allergic diseases,
      particularly for intermittent allergic rhinitis. Specific subcutaneous immunotherapy induce
      peripheral tolerance and suppress inflammation in tissue. In periphery, effector T cells
      unresponsiveness to antigens is mediated mainly by allergen specific regulatory T cells.
      Regulatory T cells induced peripherally comprise IL-10 producing type 1 regulatory T cells
      (Tr1) and regulatory T cells subset arising in vitro from CD4+CD25- and in vivo from
      peripheral memory T cells whereas naturally occurring Tregs (nTregs)originate in thymus and
      represent about 5% of the peripheral CD4 T cells and constitutively express high levels of
      the high-affinity IL-2 receptor (CD25hi). They coexpress Forkhead Box Protein P3 (Foxp3),
      glucocorticoid induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte
      associated antigen (CTLA-4), and display low expression of alpha chain of the IL-7 receptor.
      Although clinical and immunological outcomes of SIT, that are associated with regulatory T
      cells functions were profoundly studied, little is known about the molecular mechanisms that
      are crucial for nTregs activation and function in the course of SIT. Since histamine is a key
      mediator in allergy that exerts its effect through 4 types of histamine receptors we decided
      to investigate the expression of histamine 2 receptor, that has potent immunomodulatory
      properties, in regulatory lymphocytes in patients treated with SIT. Furthermore, since T cell
      receptor activation is essential for T effector lymphocytes activation we wanted to check the
      expression of zeta chain associated protein (ZAP70), that constitutes a linker between TCR
      and lower levels of intracellular downstream signal transduction, in regulatory T cells in
      the course of SIT.

      This is a 3-year prospective, placebo controlled, double blind trial of grass SIT. 41
      patients with seasonal allergic rhinitis were randomized to receive SIT (n = 21) or placebo
      (n = 20) and 15 healthy were included as a control. The primary and secondary outcomes were
      assessed at baseline and during the treatment period - before the start of the pollen season,
      at the height of the pollen season and after the end of the pollen season.Results were
      compared between the treatment year and baseline and between the groups treated with SIT,
      placebo and healthy control.
    

Intervention name(s): Allergovit; placebo
Intervention type(s): Drug; Other
Intervention description(s): commercially available grass pollen allergoid (100%), concentration A (1000 TU/ml, therapeutic units/ml)concentration B (10000 TU/ml).Patients were given subcutaneous injections with initial dose of 0.1 ml (concentration A) was increased once a 7 (+7) days until the highest tolerated dose (0.6, concentration B) was reached and SIT was continued with injections once every 4 - 6 weeks up to two years.; placebo administered with the same scheme and doses as specific subcutaneous immunotherapy
Other intervention name(s): Allergovit, grass pollen 100%, Allergopharma, Germany
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: specific subcutaneous immunotherapy; seasonal allergic rhinitis; regulatory lymphocytes; signal transduction; histamine receptor