No aluminium hydroxide or any other excipient was used. in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded. Conclusion & Clinical Relevance Intradermal immunotherapy with allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels. Keywords: allergen intradermal immunotherapy, allergoid, clinical trial, grass allergy, rhinoconjunctivitis 1.?INTRODUCTION Allergic rhinitis affects 500 million people worldwide, and its prevalence continues to Arbutin (Uva, p-Arbutin) increase in many cities. 1 This is a heavy burden for healthcare resources and is associated with significant direct and indirect costs such as work absenteeism and decreased productivity. 2 Allergen immunotherapy is the only treatment capable of changing the natural course of allergic diseases and has a long\term effect even after discontinuing the treatment. 3 , 4 , 5 , 6 , 7 Conventional immunotherapy involves the administration of high doses of the allergen during 3\5?years, by numerous subcutaneous injections or daily in the case of sublingual administration. Although both routes of administration have shown efficacy against rhinoconjunctivitis induced by sensitization to grass pollen, 8 subcutaneous Arbutin (Uva, p-Arbutin) administration is associated with a risk of systemic reaction, while sublingual administration requires daily doses that lead to a lack of adherence to the treatment. 9 The skin acts as a fundamental barrier against the exterior, enabling the individual’s immune system to interact, which encompasses, among other components, the mononuclear phagocytic series comprising macrophages, Langerhans cells and dendritic cells, forming an important link between innate and acquired immunity, representing an organ regularly used in the administration of vaccines 10 ; choosing the administration route that ensures the most effective capture and presentation of antigens by presenter cells (APCs) in the population and subpopulations of T cells responsible for specific immunological responses seems to be crucial. 11 The dermis, largely comprising connective tissue, houses a large number of T cells (CD4+ and CD8+) that practically doubles the total population of blood, 12 as well as macrophages and dermal dendritic cells. This fact justifies the intradermal (ID) administration of vaccines in active immunization. Arbutin (Uva, p-Arbutin) 13 The ID administration has shown the ability to generate humoral immune responses, equivalent to those obtained by subcutaneous (SC) or intramuscular administration (IM), but using lower doses of antigen. 14 Dendritic cells (DCs) express class I and II antigen\presenting molecules of the major histocompatibility complex, and T cells can be activated via C\type lectin receptors (CLRs) and Toll\like receptors TLRs. In this way, the DCs regulate and polarize the response of the subpopulations of T and B cells. 15 Intradermal immunotherapy with allergens was first used in 1926 by Phillips. 16 Subsequently, he expanded his study in 1933, 17 showing favourable results in more than 90% of the patients treated. The hypothesis of using the intradermal route is based on the potential reduction of IgE production, the increase in IgG and the polarization of the immune response to the Th1 pathway, due to the effective stimulation of the DCs that reside in the dermis. This was verified in murine models, using ovalbumin as an immunogen in the absence of adjuvant. 18 Similar results have been described in humans using pollen allergen extracts from administered intradermally (EudraCT 2014\004429\42 and 2012\003319\79). In the latter, the dose of 0.03?g protein was determined as that produced a negative result in the intradermal skin test with (largest papule diameter 2.9?mm), 15?minutes after administration. The main objective of the present research was to study the efficacy of a polymerized vaccine administered intradermally, at different doses, by means of combined symptom and medication scoring. Six doses of the product under investigation were administered pre\seasonally during two consecutive pollen seasons. The data obtained were compared with the placebo group. As secondary objectives, we proposed to study the safety of the intradermal route for the administration of immunotherapy with allergoids, the local tolerance of the allergen by the patient through conjunctival provocation test and the study of the variations produced Arbutin (Uva, p-Arbutin) in the levels of immunoglobulins before and after each cycle of immunotherapy. 2.?METHODS 2.1. Trial design A multicentre, randomized, double\blind, parallel\group placebo\controlled clinical trial of intradermal immunotherapy (IDIT) with Arbutin (Uva, p-Arbutin) two different doses of a polymerized extract of (Laboratorios Diater SA) in Rabbit Polyclonal to GPR153 patients with allergic rhinoconjunctivitis or rhinitis to grass pollen was designed. The administration.