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Immunotherapy

Immunotherapy involves the administration of small amounts of antigen to which a patient has been shown to be sensitive in increasing doses over time to desensitize the patient to those antigens. It is the third treatment strategy that is used for the management of patients with AR and is an alternative that should be considered in patients who are unresponsive to medications and allergen avoidance. In traditional immunotherapy, small yet increasing amounts of antigen are injected subcutaneously to decrease the patient's responsiveness to those antigens. The safety and efficacy of immunotherapy in the treatment of AR has been well established, although there is a very slight ris of both local and systemic reactions during the administration of subcutaneous immunotherapy. !ommon mechanisms involved in the physiologic efficacy of immunotherapy are discussed in the chapter on allergy and immunology. Immunotherapy decreases the response of the patient to those antigens in the vaccine. The benefit of specific immunotherapy is not immediate but begins within the first several months. To achieve sustained benefit from immunotherapy, treatment for at least " to # years is recommended. Although immunotherapy continues to be delivered primarily through the subcutaneous route, there is increasing evidence demonstrating both the safety and efficacy of immunotherapy delivered sublingually $%&'. (ecause immunotherapy is involved in modulating the immune response, it is not of benefit in patients with nonallergic rhinitis.

Allergen)specific immunotherapy $*IT' is used to provide relief for patients with severe symptoms because it modulates the mechanisms of allergic symptoms, thereby reducing symptoms and alleviating the need for daily medications. Immunotherapy has been shown to be clinically effective several years after treatment was stopped. A retrospective study of end) organ symptom improvement in those undergoing immunotherapy showed significant improvement of nasal, otologic, ocular, and laryngeal symptoms during and % years after therapy. +ollen immunotherapy in children with seasonal allergic rhinoconjunctivitis was also found to decrease bronchial hyperresponsiveness and development of asthma symptoms % years after treatment in a multicenter, controlled trial of children , to -. years old. The immune mechanisms behind the clinical improvements after successful immunotherapy are not fully nown. /uring *IT, Ig0. antibodies have been found to bloc Ig1 activity, which also leads to decreased release of preformed mediators from mast cells and basophils in the immediate response. In the late response, these 234bloc ing235 antibodies can also act to prevent the Ig1)mediated presentation of antigen to T cells. Another modulating feature of immunotherapy is thought to be that of the influence of T)cell subsets under conditions of immunotherapy. *ome studies have shown a shift away

from a Th% cyto ine bac ground to that of a Th- cyto ine profile after specific immunotherapy. *uccessful grass pollen immunotherapy in a study by 6achholz et al. $%7' showed an increase in the ratio of I89):; to I<)# mR9A= cells in the nasal mucosa, providing evidence for T)cell)subset switching at the protein level. *ignaling lymphocyte activation molecule $*<A>', a Th-)associated gene, was studied in a pollen immunotherapy study of clinical symptoms. *ymptom improvement in allergic patients was associated with a rise of *<A> e?pression when T lymphocytes were stimulated with pollen e?tracts in vitro Another study of *IT in mite)sensitive asthma showed an increase in the I89):; to I<). ratio with improved symptom scores, again showing the shift away from an allergic Th% profile to that of a Th- profile. 6hether immunotherapy affects T)cell subsets in the periphery remains controversial, with conflicting results by numerous investigators. T)cell responses accounting for the inflammation and cytoto?ic effects seen in the mucosa are down)regulated by T08):@. T08) :@, a major regulatory cyto ine with effects on ( and T cells as well as macrophages, bloc s effector function of T cells $"A'. These results point toward an immunoregulatory or suppressive mechanism in *IT. Another promising area in immunotherapy that is currently under study is that of sublingual immunotherapy. 6ith hope for an immune modulation option for children, this area has shown promise in decreasing medication use in allergic rhinitis and possibly in reducing the development of allergic asthma in children. +rolonged treatment appears to show efficacy in decreasing nasal symptoms $"-'. Its efficacy compared with *IT needs to be studied.

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