Singh, Iesha (2018) Novel therapeutic approaches for treating allergic rhinitis. (PhD thesis), Kingston University, .

Abstract

Allergic rhinitis is a most common IgE-mediated type 1 hypersensitivity disorder cause by exposure of aeroallergens. Allergen immunotherapy is an only curative treatment of allergic rhinitis, with disease modifying effect and efficacy following withdrawal of immunotherapy. Despite AIT being most effective mode of treatment, still it is related to poor patient compliance and adverse effects like anaphylaxis. This study aims to investigate novel approaches of treatment involved in inducing tolerance in allergic patients. Studies have shown that use of engineered recombinant allergen peptides targeting T and B cell epitopes and passive immunisation act as a novel approach of treatment. This study reports the potential of short course treatment with hydrolysed peptides in order to induce clinical benefits in grass pollen allergic patients. Here, PBMCs from 'Lolium perenne' peptide (LPP) immunotherapy treated patients was utilised to investigate the immunological mechanism involved by immune modulation in T and B cells. Further, using cat allergy model it was demonstrated that passive administration of two monoclonal antibodies (R1908/9) against Fel d 1 epitopes was able to suppress nasal symptoms following intranasal allergen challenge. Therefore, our study confirms the mechanisms underpinning the rapid, long-term clinical effect of R1908/9 and provides a rational for Fel d 1 passive immunotherapy for allergic respiratory disease with/without asthma. This thesis also comprises of data suggesting role of lung surfactant protein D (rfh SP-D) as an immunomodulator involved in suppressing both late and early phase of allergic responses. Here, it was sought to elucidate the effect of frhSP-D on Fc[epsilon]RI and CD23 mediated grass pollen induced allergic inflammatory responses. In this study, it was first time shown that rfhSP-D inhibits allergenn-induced basophil response at a single cell level and suppressed CD23-mediated facilitated allergen presentation and Th2 cytokine production. In addition, rfhSP-D also inhibits IgE synthesis by B cells, which is a novel observation. This thesis highlights the significance of novel approach of treatment involved in inducing tolerance and stimulating the clinical benefits.

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