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 . allergic diseases are most likely due to complex interactions between largely unknown genetic and environmental factors [ 36 ] . the micro - array techniques for the detection of specific ige have improved the diagnostic procedures for allergic diseases . 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 . 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 . 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 . trail is also seen as the basis for a  miracle  drug for cancer because of its ability to selectively kill cancer cells . it has previously been reported that negative selection of t cells in the thymus is controlled by trail . for example , mice deficient in trail had a severe defect in thymic deletion of t cells and were hypersensitive to collagen - induced arthritis . 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 . 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 . the study was conducted in antalya , turkey between 9 january 2009 and 28 january 2010 . the study was approved by the local ethics committee , and written consent was obtained from all patients and healthy volunteers . all patients were followed in the immunology and allergy clinic of antalya education and research hospital . subjects with kidney disease , heart disease , liver disease , diabetes mellitus , cancer status , obesity , ( body mass index ( bmi ) 30 kgm ) , and autoimmune disease were excluded clinically and serologically . the first group of 25 patients included 11 male and 14 female subjects with allergic rhinoconjunctivitis , having a combined mean age of 38.5612.03 years . the first group included 2 measurements in the same patients ; group - ia represents data recorded before subcutaneous allergen - specific immunotherapy , and group - ib shows data recorded 12 months after the subcutaneous allergen - specific immunotherapy . all patients received immunotherapy every 4 weeks . the symptoms and severity of allergic reactions were recorded before and after treatment . a second group of 25 healthy individuals ( 11 male and 14 female ) ( group ii ) had a mean age of 38.2312.21 years ( table 1 ) . subjects with kidney disease , heart disease , liver disease , diabetes mellitus , cancer status , obesity ( body mass index ( bmi ) 30 kgm ) , and autoimmune disease were excluded clinically and serologically . blood samples were collected into 5 ml plain vacutainer tubes and centrifuged at 3000  g for 10 min . serum ige levels , hepatitis markers ( hbs ag , anti hbs , anti hcv ) were evaluated in all patients . total and specific ige levels were enumerated by fluoroenzyme immunoassay ( immunocap - feia ) using an immunocap kit ( phar - macia , uppsala , sweden ) . values above 100 ku / l and 0.35 ku / l for total and specific ige levels were considered abnormal . serum strail levels in all individuals ( patients and healthy controls ) were measured by a sandwich enzyme - linked immunosorbent assay ( diaclone , france ) . skin prick tests on the forearm were performed in all patients , using standardized latex extract containing high ammonia natural rubber latex , and a full set of 10 common allergens . in addition , venom spt was performed on 1 patient based on the subject s clinical history . student s t test was used for comparison of controls and patient groups ( group ia and group ib ) . the study was conducted in antalya , turkey between 9 january 2009 and 28 january 2010 . the study was approved by the local ethics committee , and written consent was obtained from all patients and healthy volunteers . all patients were followed in the immunology and allergy clinic of antalya education and research hospital . subjects with kidney disease , heart disease , liver disease , diabetes mellitus , cancer status , obesity , ( body mass index ( bmi ) 30 kgm ) , and autoimmune disease were excluded clinically and serologically . the first group of 25 patients included 11 male and 14 female subjects with allergic rhinoconjunctivitis , having a combined mean age of 38.5612.03 years . the first group included 2 measurements in the same patients ; group - ia represents data recorded before subcutaneous allergen - specific immunotherapy , and group - ib shows data recorded 12 months after the subcutaneous allergen - specific immunotherapy . all patients received immunotherapy every 4 weeks . the symptoms and severity of allergic reactions were recorded before and after treatment . a second group of 25 healthy individuals ( 11 male and 14 female ) ( group ii ) had a mean age of 38.2312.21 years ( table 1 ) . subjects with kidney disease , heart disease , liver disease , diabetes mellitus , cancer status , obesity ( body mass index ( bmi ) 30 kgm ) , and autoimmune disease were excluded clinically and serologically . blood samples were collected into 5 ml plain vacutainer tubes and centrifuged at 3000  g for 10 min . serum ige levels , hepatitis markers ( hbs ag , anti hbs , anti hcv ) were evaluated in all patients . total and specific ige levels were enumerated by fluoroenzyme immunoassay ( immunocap - feia ) using an immunocap kit ( phar - macia , uppsala , sweden ) . values above 100 ku / l and 0.35 ku / l for total and specific ige levels were considered abnormal . serum strail levels in all individuals ( patients and healthy controls ) were measured by a sandwich enzyme - linked immunosorbent assay ( diaclone , france ) . skin prick tests on the forearm were performed in all patients , using standardized latex extract containing high ammonia natural rubber latex , and a full set of 10 common allergens . in addition , venom spt was performed on 1 patient based on the subject s clinical history . student s t test was used for comparison of controls and patient groups ( group ia and group ib ) . in this clinical follow - up study , 25 patients were already receiving subcutaneous immunotherapy , and these subjects were included for further analysis at our clinic . the mean ige levels were : group ia  699.505 iu / ml ; group ib  164.115 iu / ml ; and group ii 41.08 iu / ml . there was a statistically significant difference between the values of the research group before and after immunotherapy ( p=0/0005 ) . prick tests in all patients in group i were detected in mite , olive and grass allergy . these results correlated with specific ige , and hepatitis markers were negative in all patients . as shown in figure 1 , significant difference was seen in the mean values of strail in allergic rhinitis patients before immunotherapy ( n=25 ; 939.85352.52 pg / ml ) , afterc immunotherapy ( n=25 ; 628.93170.5 pg / ml ) and healthy controls ( n=25 ; 612.64135.6 pg / ml ) . there was a statistically significant difference between the values of the research group before and after immunotherapy ( p=0.001 ) . while there was a statistically significant difference between the pre - treated group and control group ( p<0.0001 ) , there was no difference between the post - treated group and healthy individuals ( p=0.801 ) . as shown in table 3 , there was a statistically significant difference between the values of the research group before and after immunotherapy ( grasses mixture , barley mixture , oleaauropeae , d. pteronyssinus , d. farinae ) in this clinical follow - up study , 25 patients were already receiving subcutaneous immunotherapy , and these subjects were included for further analysis at our clinic . the mean ige levels were : group ia  699.505 iu / ml ; group ib  164.115 iu / ml ; and group ii 41.08 iu / ml . there was a statistically significant difference between the values of the research group before and after immunotherapy ( p=0/0005 ) . prick tests in all patients in group i were detected in mite , olive and grass allergy . these results correlated with specific ige , and hepatitis markers were negative in all patients . as shown in figure 1 , significant difference was seen in the mean values of strail in allergic rhinitis patients before immunotherapy ( n=25 ; 939.85352.52 pg / ml ) , afterc immunotherapy ( n=25 ; 628.93170.5 pg / ml ) and healthy controls ( n=25 ; 612.64135.6 pg / ml ) . there was a statistically significant difference between the values of the research group before and after immunotherapy ( p=0.001 ) . while there was a statistically significant difference between the pre - treated group and control group ( p<0.0001 ) , there was no difference between the post - treated group and healthy individuals ( p=0.801 ) . as shown in table 3 , there was a statistically significant difference between the values of the research group before and after immunotherapy ( grasses mixture , barley mixture , oleaauropeae , d. pteronyssinus , d. farinae ) allergen - specific immunotherapy has been used in the management of allergic diseases for nearly 100 years . 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% . 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 . 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 [ 1316 ] . 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 . engagement of the fas / fasl system has not yet been shown to contribute to increase apoptosis . 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 [ 1721 ] . 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- ) , 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 . 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 [ 2427 ] . the regulation of mc numbers , as of any other normal cells , depends on both their generation rate and survival time within tissues . 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 . allergic mechanism are involved in the increased susceptibility of human mc to trail - induced apoptosis after ige - dependent activation . 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 .
summarybackgroundallergic rhinitis is a common health problem affecting the immune system . 
 the homeostasis of the immune system is regulated by apoptosis . in this study , 
 serum circulating soluble trail levels of allergic rhinoconjunctivitis patients before and after allergen - specific immunotherapy were evaluated.material/methodsthe strail levels of pre- and post - treated allergic rhinoconjunctivitis patients ( n=25 ) were compared to age- and sex - matched healthy individuals ( n=25 ) . 
 strail levels were measured by elisa . the skin prick test ( spt ) 
 results were recorded before and after treatment.resultsthe strail levels between the pre - treated and control groups were significantly different ( p<0.0001 ) . 
 however , there was no significant difference between the post - treated group and healthy individuals ( p=0,801 ) . 
 spt was a statistically significant difference between the values of the research group before and after immunotherapy ( grasses mixture , barley mixture , oleaauropeae , d. pteronyssinus , d. farinae).conclusionsthe strail levels were decreased after allergen - specific immunotherapy to healthy levels and may be of use as a marker of efficacy of immunotherapy in allergic rhinoconjunctivitis patients .