Der P10 Research Articles

Оцінка сироваткового загального та специфічного імуноглобуліну Е в дітей з персистуючим алергічним ринітом і поєднаним із бронхіальною астмою при сенсибілізації до алергенів кліщів

Allergic rhinitis (AR) is a common immunoglobulin E (IgE) dependent disease among allergic patients worldwide. At the same time, the determination of specific IgE in the blood serum allows characterizing the relevant sensitizing allergens. Despite the existence of conditional thresholds for normal and elevated levels of total and specific IgE, there is no consensus in the literature on which IgE value unequivocally confirms the presence of atopy and what is the relationship between these levels and the severity of clinical manifestations. Purpose - to evaluate the levels of serum total and specific IgE and their relationship with severity and age in children with persistent AR and combined with bronchial asthma (BA) during sensitization to house dust mite (HDM) allergens. Materials and methods. A clinical, anamnestic and laboratory examination of 259 children aged 5 to 17 years with AR and combined AR with BA, who were sensitized to HDM allergens, was conducted. Results. In AR in children with sensitization to HDM, there is a dependence of serum total IgE level on the severity of AR and age of children. With increasing severity of AR manifestations, a significant (p<0.05) increase in total IgE levels was noted. It was found that the content of sIgE also increased with increasing severity of AR. Thus, statistically significantly (p<0.05) higher levels of sIgE were determined in sensitization to the major HDM molecules Der f 1, Der p 1, Der p 2, Der p 23 in children with severe AR. Sensitization to the tropomyosin Der p10 molecule, which usually has no effect on the clinical manifestations of respiratory allergy but indicates cross-reactivity to seafood, was significantly more common (p<0.05) in children aged 3-7 years compared to children aged 13-17 years. Conclusions. The data obtained partially define the pathogenetic features in the formation of sensitization to HDM and their individual molecules, confirming that this process begins at an early age, which may indicate the need to start allergen-specific immunotherapy in such children if clinically necessary. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Tropomyosin in mugwort cross-reacts to house dust mite, eliciting non-Th2 response in allergic rhinitis patients sensitized to house dust mite

BackgroundMugwort and house dust mite (HDM) are two of the most common inhalant allergens in Asia, however, whether mugwort affects polysensitized HDM+ allergic rhinitis (AR) patients has not been elucidated.MethodsOverall, 15,884 AR outpatients were assessed for clinical status. Amino acid sequences of mugwort were determined by mass spectrometry. Afterward, cross-reactivity between mugwort tropomyosin and Dermatophagoides pteronyssinus 10 (Der p10) was analysed by ELISA inhibition and basophil activation experiments. To compare immunologic responses eliciting by two different tropomyosins, peripheral blood mononuclear cells (PBMCs) of HDM-monosensitized patients were stimulated by mugwort, HDM, Der p10 and synthetic peptides representing mugwort tropomyosin respectively.ResultsPolysensitized HDM+AR patients were mainly sensitized to cat and mugwort, and the positive rate of monosensitized HDM+AR out-clinic patients was increased during the mugwort pollen season. Tropomyosin protein was able to find in mugwort. Synthetic tropomyosin peptide of mugwort activated basophils which were primed by HDM-specific IgE; ELISA inhibition experiment showed synthetic tropomyosin peptide of mugwort inhibited IgE binding to HDM tropomyosin, Der p10. Unlike HDM and Derp 10, mugwort and mugwort tropomyosin mainly induced IFN-γ and IL-17 release in PBMCs of monosensitized HDM+AR patients, but not IL-5.ConclusionsPan-allergen tropomyosin accounts for the cross-reactivity between mugwort and HDM, which reminds HDM+ patients to reduce mugwort exposure in mugwort pollen season in virtue of the tropomyosin induced mild inflammation.

СЕНСИБІЛІЗАЦІЯ ДО АЛЕРГОКОМПОНЕНТІВ КЛІЩІВ ДОМАШНЬОГО ПИЛУ У ДІТЕЙ З БРОНХІАЛЬНОЮ АСТМОЮ В УКРАЇНІ

SENSITIZATION TO ALLERGENIC COMPONENTS OF HOUSE DUST MITES IN CHILDREN WITH BRONCHIAL ASTHMA IN KHARKIV REGION V. A. Klymenko1 , T. V. Kulik1 , V. M. Belous2 , O. V. Pyontkovskaya3 , O. M. Savvo3 1 Kharkiv National Medical University, Kharkiv, Ukraine 2 Ecomed Medical Center, Kharkiv, Ukraine 3 Municipal non-profit enterprise of Kharkiv Regional Council «Regional Children’s Clinical Hospital G1», Kharkiv, Ukraine Abstract. The aim of the work is to determine the molecular profile of sensitization to house dust mites in children with bronchial asthma in the Kharkiv region. Object and methods of study. 42 children aged from 6 to 18 years were under observation. Evaluation of the sensitization profile was performed by the method of multicomponent photometric analysis ALEX. Results and discussion. Boys predominated among the patients — 76 %. Patients had intermittent (46 %), mild persistent (31 %), moderate persistent (15 %) and severe persistent asthma (8 %). Allergic rhinitis was noted in 88 % of patients. Elevated IgE levels were observed in 69 % of patients. The median IgE is 385.50 [122.75; 991.00] kU/L. Sensitization to house dust mites was detected in 23 (54 %) patients, of which monosensitization — 10 %; co-sensitization with other aeroallergens — 44 %. Among pediatric patients in the Kharkiv region, the leading sensitization is sensitization to D. farinae (44 %) and D. pteronyssinus (48 %). Molecular sensitization profile: Der f1 — 38.1 %; Der f2 — 38.1 %; Der p1 — 33.33 %; Der p2 — 38.1 %; Der p5 — 14.29 %; Der p7 — 16.67 %; Der p10 — 9.52 %; Der p20 — 2.38 %; Der p23 — 26.19 %. Only minor components (Der p5, 7, 10, 20 or 21) were found in 7.14 % of patients, which proves the need for molecular diagnosis when prescribing immunotherapy. Among the «new» allergens for our region — Blomia tropicalis — sensitizationin 11.9 %; molecular profile: Blo t1 — 2.38 %; Blot 10 — 9.52 %; Blo t21 — 4.76 %. Isolated cases of sensitization to ticks Glycyphagus domesticus, Tyrophagus putrescentiae, Lepidoglyphus destructor have been identified. Conclusions. Differences in sensitization to molecular components of house dust mites in children of the Kharkiv region were proved . It should be taken into account in the diagnosis and treatment of patients with allergic diseases. Key words: bronchial asthma, sensitization, house dust mites, molecular components.

96 Sublingual allergen-specific immunotherapy in pediatric patients: biomarkers and molecular allergy diagnostics as predictors of therapeutic success

Abstract Background Efficacy of allergen-specific immunotherapy (ASIT) in patients with asthma could be significantly enhanced when physicians have an opportunity to identify those who are most likely to respond, determine when to stop treatment, and predict relapse. Thus, molecular allergy diagnostic is an effective tool that could help to individualize the diagnosis and treatment of asthma by accurate detection of the causative and cross-reactive allergens in pediatric patients. Cytokines are known as reliable diagnostic and prognostic biomarkers for asthma and can be used to evaluate the therapeutic effect. Objectives To evaluate the roles of molecular allergy diagnostic and biomarkers (L-10, IFNγ и TGFβ) as predictors of ASIT efficacy in pediatric patients with asthma. Design/Methods Eighty children aged 5 to 18 years with mild and moderate atopic bronchial asthma were included in the study. Sixty-eight out of 80 (85%) were found to have sensitization to house dust mites Dermatophagoides Pteronyssinus and/or Dermatophagoides Farinae. All these patients underwent molecular diagnostics using ImmunoCAP (Phadia 100) to determine the major (r Der p1, r Der p 2) and minor allergens (r Der p10) of the house dust mites. Twenty-eight patients with mild and moderate asthma were found to have a high sensitivity to these allergens and received SLIT with a mixture of house dust mites (Dermatophagoides Pteronyssinus and/or Dermatophagoides Farinae). To compare the efficacy of SLIT, we evaluated the severity of asthma clinical symptoms on a point scale from 0 to 3, and biomarker levels (IL-10, IFNγ и TGFβ) before and 6 months after SLIT. Twelve healthy children were included in the study as a reference group. Results At the beginning of the study, the average daily score in the SLIT group of 2.5 ± 0.7, and after 6 months of treatment, it decreased to 0.5 ± 0.2. The levels of biomarkers were markedly decreased prior to the treatment, especially TGFβ levels, and normalized at the end of treatment (Tab.1). Conclusion These findings support the efficacy of molecular diagnosis to determine the efficacy of allergen-specific immunotherapy in patients with asthma.

Diagnosis of allergic sensitization in patients with allergic rhinitis and asthma in a tropical environment.

Few studies in tropical developing countries have utilized molecular diagnosis to characterize allergen-specific responses to aeroallergens. To investigate the in vivo and in vitro responses of IgE antibodies to inhalant allergens in allergic patients with rhinitis and/or asthma. A prospective study in which patients with allergic rhinitis and/or asthma were included. Skin prick tests with 16 inhalant extracts of allergens were carried out and total and specific IgE levels for allergens and their molecular components in the serum were determined. In a total of 189 patients, 73.5% showed high levels of total IgE in the serum. The prick tests were positive for the following allergens: Dust mite extracts; more than 60 %, cat; 29.6 %, dog; 23.4 %, and Periplaneta Americana; 21.6 %. Specific IgE for Dermatophagoides farinae and Pteronyssinus was present in 66.6 % of the patients; for Blomia tropicalis; in 45.0 %, for Ascaris lumbricoides; in 24.7 %, for cat; in 17.3 %, for parrot feathers; in 14.8 %, and for Penicillium notatum; in 12.3 %. IgE antibodies to mite allergens of group 1 and 2 were present in 59.0 % and 70.1 % of the sera; 39.1 % contained IgE to rBlo t5, 30.4 %contained rBla g4, 19.9 % contained rFel d1, 11.8 % contained rArt v3, 11.2 % contained Der p10, 9.9 % contained rBla g2, 9.3 % contained rPer a7, 9.3 % contained nFel d2, and 8.7 % contained rCan f1. This study confirms that mites are the main sensitizing agents in patients with respiratory allergic diseases in a tropical environment. There was a good correlation between the results of the skin tests and the results of the in vitro tests.

The Dermatophagoides pteronyssinus Molecular Sensitization Profile of Allergic Rhinitis Patients in Central China.

Background House dust mites (HDMs) are the major aeroallergens in patients with rhinitis and/or asthma in China. However, the molecular sensitization of HDM is varied in different regions. Objective To investigate the Dermatophagoides pteronyssinus ( Der p) molecular sensitization profile of allergic rhinitis (AR) patients in Central China. Methods AR patients with positive skin prick tests to Der p were enrolled in our study. Specific immunoglobulin E (sIgE) for Der p, Dermatophagoides farinae ( Der f), Acarus siro ( Aca s), Blomia tropicalis ( Blo t), and Der p components Der p1, Der p2, and Der p10 were measured in all patients. Results A total of 130 patients were included. The overall prevalence of positive serum sIgE was 99.2% for Der p, 98.5% for Der f, 81.5% for Aca s, 83.1% for Blo t, 71.5% for Der p1, 64.6% for Der p2, and 11.5% for Der p10. HDM-AR patients with asthma displayed significantly higher concentrations of sIgE to Der p, Der f, Der p1, and Der p2 than did those without asthma ( P < .001). The prevalence of asthma in HDM-AR patients was higher among the patients sensitized to both Der p1 and Der p2 (62.8%) than those sensitized to only 1 allergen ( Der p1 26.7% or Der p2 16.7%; P < .05) or nonsensitized to Der p1 and Der p2 (19.4%; P < .001). Conclusion Der p has high cross-reactivity with other mite species. Der p1 and Der p2 are the major components to induce Der p sensitization among AR patients in Central China. Sensitization to both Der p1 and Der p2 may be a risk factor for developing asthma in HDM-AR patients.

Prevalence, molecular characterization, and clinical relevance of sensitization to Anisakis simplex in children with sensitization and/or allergy to Dermatophagoides pteronyssinus.

Prevalence of the Anisakis Simplex's (AS) sensitization in children sensitized to Dermatophagoides pteronissynus (DP) is not known, neither it is to which percentage it might be due to cross-reactivity. The primary objective of the present retrospective cross-sectional study is to evaluate the prevalence of sensitization to AS in children sensitized or allergic to DP. Secondary outcomes were the prevalence of cross-reactivity and clinical relevance of the condition. The prevalence of sensitization to AS differs significantly among patients sensitized and not to DP (13.43% vs. 3.80%; p=0.019). The higher prevalence is mainly due to cross-reactivity with Der p10 (OR=8.86; 95% CI=4.33-40.74; p=0.0001). Currently, the sensitization to AS seems to have no clinical relevance in the pediatric population.

IgE responses to Ascaris and mite tropomyosins are risk factors for asthma.

The relationship between helminthiases and allergy is a matter of considerable interest and research. In the tropics, house dust mite exposure, a known risk factor for asthma, is frequently concurrent with helminth infections. It remains to be defined whether infection with the common roundworm Ascaris or its bystander immunological effects influence the prevalence and pathogenesis of asthma independently of mite sensitization. To investigate the relationship between the IgE responses to Ascaris and its purified allergens and the risk of asthma in a tropical country. A nested case-control study was performed in 356 subjects who reported current and past asthma symptoms (asthmatics) and 435 controls that had never experienced such symptoms. They were tested for serum levels of total IgE and specific IgE to Ascaris extract, Asc s 1 (ABA-1), Asc l 3 (tropomyosin) and GST (glutathione transferase). In addition, specific IgE to Dermatophagoides pteronyssinus, Blomia tropicalis and their tropomyosins Der p 10 and Blo t 10 was measured. Sensitization was defined as a positive specific IgE result to any extract or recombinant allergen. Sensitization to Ascaris and D. pteronyssinus was independently associated with asthma after adjustment for age, gender, socio-economic stratum, city and other IgE levels (adjusted ORs: 2.17; 95% CI 1.37-3.42 and 2.46; 95% CI 1.54-3.92), respectively. There was also a significant association with sensitization to the highly allergenic and cross-reactive tropomyosins Asc l 3, Blo t 10 and Der p10 (aORs: 1.76; 95% CI 1.21-2.57, 1.64; 95% CI 1.14-2.35 and 1.51; 95% CI 1.02-2.24), respectively. IgE responses to Ascaris are associated with asthma symptoms in a population living in the tropics. Sensitization to the cross-reactive Ascaris and mite tropomyosins partially underlies this finding. These results have potential relevance in asthma diagnosis and management.