Allergic rhinitis is a common health problem and has 2 forms seasonal and perennial. The prevalences of asthma, allergic rhinitis and allergic eye disease in Antalya, on the south coast of Turkey, have been reported as 8.2%, 10.8% and 7.5%, respectively [¹,²]. Allergic diseases are most likely due to complex interactions between largely unknown genetic and environmental factors [³–⁶]. The micro-array techniques for the detection of specific IgE have improved the diagnostic procedures for allergic diseases. This method also allows definition of sensitization profiles from an epidemiological point of view [⁵].

A detailed knowledge of the sensitization pattern may have relevant implications for the prescription of specific immunotherapy. A number of epidemiologic studies have also supported a relationship between allergic rhinoconjunctivitis and diet, hygiene, and life-style, suggesting that environmental factors also impact the development of allergic rhinoconjunctivitis. Apoptosis is an active physiological process that can cause an inflammatory reaction and tissue damage, and is fundamental to maturation and homeostasis in the immune system [⁷]. It can be induced passively, through lack of essential survival signals, or actively, through ligand-induced trimerization of specific death receptors of the tumor necrosis factor (TNF) receptor family, such as Fas, the TNF receptor, or the TNF-related apoptosis-inducing ligand (TRAIL) receptor [⁸]. TRAIL also is able to prevent apoptosis through the actions of its decoy receptors, DcR-1 and DcR-2. Various regulators of TRAIL include FADD, IAPs, Bcl-2s, p53, and FLIPs. TRAIL is present in cells involved in asthma, including eosinophils, mast cells, fibroblasts, and airway epithelial cells. It is expressed in airway remodeling and may be linked with the pathways of transforming growth factor beta1, which is thought to cause damage to the epithelium. The repair process of the epithelium is hindered as a result of increased apoptosis induced by TGF-beta1, which overlaps with the pathways of TRAIL. Analogs of TRAIL could have therapeutical applications for asthma. TRAIL is also seen as the basis for a “miracle” drug for cancer because of its ability to selectively kill cancer cells [⁹]. It has previously been reported that negative selection of T cells in the thymus is controlled by TRAIL [¹⁰]. For example, mice deficient in TRAIL had a severe defect in thymic deletion of T cells and were hypersensitive to collagen-induced arthritis [¹¹].

Mast cells activation through Fc epsilon RI cross-linking has a pivotal role in the initiation of allergic reactions. IgE-dependent activation increases TRAIL-induced caspase-8 and caspase-3 cleavage, and regulates human mast cell apoptosis by fine-tuning anti-apoptotic and pro-apoptotic factors [¹²]. Our study aimed to identify the role of sTRAIL in the pathophysiology of allergic rhinoconjunctivitis, and to explore whether allergen-specific subcutaneous immunotherapy treatment of allergic rhinoconjunctivitis patients altered any observed effect of sTRAIL.

Allergen-specific immunotherapy has been used in the management of allergic diseases for nearly 100 years. The quality of allergen products is a key issue for both diagnosis and therapy. The results of our previous study suggest that in our region 51.8% of the allergens determined by prick test are mite and 42.3% are pollens. Pollen positivity rate of the cases that had immune-therapy was 61.8%, and mite positivity rate was 60.4%. Most of the cases had rhinitis symptoms due to pollens and mite. Allergens are known to exhibit regional variation in expression, which suggests that the allergen profiles and skin prick tests should be designed with reference to individual locales [²]. Allergen-specific immunotherapy treatment significantly reduced the nasal symptom score across all group I patients studied. In this study, SPT was a statistically significant difference between the values of the research group before and after allergen-specific subcutaneous immunotherapy (Grasses mixture, Barley mixture, Oleaauropeae, D. Pteronyssinus, D. farinae).

Our earlier studies provided a novel perspective on severe persistent allergic asthma and the effect of anti-IgE treatment, using as markers serum soluble TNF-related apoptosis-inducing ligand, total antioxidant capacity, hydrogen peroxide, malondialdehyde, ceruloplasmine oxidase activity, high sensitive C reactive protein and total nitric oxide concentrations measurements [¹³–¹⁶]. In our previous study we found that the TRAIL levels in variances of the patients who had the effective anti IgE treatment were significantly lower than the healthy controls [¹⁶].

Engagement of the Fas/FasL system has not yet been shown to contribute to increase apoptosis. However, the importance of the other death pathways is still unknown. Recent interest has focused on the molecule TRAIL, which is involved in the pathophysiology of different diseases, including cancer, diabetes mellitus, autoimmune diseases, and inflammation [¹⁷–²¹]. TRAIL also present in cells that involved in asthma including eosinophils, mast cells, fibroblasts, and airway epithelial cells. It is expressed in airway remodeling and may be linked with the pathways of transforming growth factor-beta (TGF-β), which is thought to cause damage to the epithelium. The repair process of the epithelium is hindered as a result of increased apoptosis induced by TGF-beta, which overlaps with the pathways of TRAIL. Moreover analogs of TRAIL could have therapeutical applications for asthma [²²,²³]. These results reflect the different mechanism(s) in the pathogenesis of allergic diseases by the regulation of apoptosis.

Desloratadine (DCL) is a non-sedating antihistamine approved for the treatment of allergic rhinitis. Patients in groups I-A and B had a DCL usage history during the exacerbation phase from May to November. Blood samples from the patients were obtained in January, when they would be expected to have fewer allergic symptoms. Mast cells (MC) play a key role in allergy and are involved in several chronic inflammatory diseases. Furthermore, they are involved in innate immunity and in tissue repair [²⁴–²⁷]. MC hyperplasia is observed in certain disease states [²⁶]. The regulation of MC numbers, as of any other normal cells, depends on both their generation rate and survival time within tissues. Many factors regulate MC viability [²⁴]. The critical event in allergic reactions is allergen-induced crosslinking of specific IgE molecules bound to Fc_RI receptors on the MC surface, which triggers MC degranulation and release of inflammatory mediators. Non-IgE-mediated activation may also contribute to continued degranulation of MC during the late phase of allergic reactions [²⁴]. Allergic mechanism are involved in the increased susceptibility of human MC to TRAIL-induced apoptosis after IgE-dependent activation [²⁵]. In this study, IgE levels had a statistically significant difference between the values of the research group before and after allergen-specific subcutaneous immunotherapy.

Taken together, our results and those of others, suggest that characterization of the specific receptor systems activated, and the pro-inflammatory factors regulated, by TRAIL in vivo may lead to the development of novel therapeutic strategies for diseases as diverse as infection, autoimmunity, and allergy.

fn8-medscimonit-18-10-cr617Source of support: Departmental sources

Reginald Gorczynski.