House Dust Mite Allergen Extracts Research Articles

Absence of IgE neosensitization in house dust mite allergic patients following sublingual immunotherapy

The impact of sublingual immunotherapy (SLIT) on IgE neosensitization remains to be evaluated in large cohorts of patients. The aim of this study was to assess the dynamics of antibody responses induced in patients with allergic rhinitis during a 12-month treatment with sublingual tablets of house dust mites (HDM) allergen extracts. Antibody responses were assessed in relationship with neosensitization and clinical benefit in sera from 509 European house dust mite-allergic patients before and after 1year of daily sublingual immunotherapy, using tablets containing Dermatophagoides pteronyssinus plus D farinae extracts or placebo (ClinicalTrials.gov NCT00674700). Patients were followed for one additional year after treatment cessation. IgE and IgG4 antibodies specific for mite extracts or purified group 1, 2 and 10 allergens were assessed using Immulite, Immunocap and ISAC assays. After 1year of SLIT, mite-specific IgE and IgG4 titres increased by 1.5-fold and fourfold, respectively, in the active, but not in the placebo group. A strong IgG4 induction occurred in a subgroup (i.e. 10-15%) of "immunoreactive" patients, without any correlation with improvement in the average adjusted symptom score. Pre-existing IgE levels to purified mite allergens were not impacted during immunotherapy, and no de novo IgE responses to group 1, 2, 10 allergens were induced in patients who were unsensitized prior to immunotherapy. Similarly, no IgE neosensitization to wheat germ or yeast components used in the mite culture medium was observed. We document in a cohort of 509 patients followed over a 2-year period that SLIT does not induce any IgE neosensitization to allergens contained in the vaccine, such as groups 1, 2 as well as the food-related group 10 allergen. This observation further corroborates the safer safety profile of SLIT over SCIT.

Standardization of House Dust Mite Extracts in Korea

PurposeHouse dust mites are the most important cause of respiratory allergy in Korea. Standardization of allergen extracts is essential for improving diagnostics and immunotherapeutics. This study was undertaken to evaluate the allergenicity of standardized house dust mite allergen extracts from Korean house dust mite isolates.MethodsAllergen extracts were prepared from cultured Korean house dust mites (Dermatophagoides farinae and D. pteronyssinus). Allergenic activities of Korean house dust mite extracts were compared to standardized extracts from a company in the United States whose allergen concentrations were expressed as Allergy Units (AUs). Specifically, we compared group 1 and 2 major allergens using two-site enzyme-linked immunosorbent assay (ELISA) kits and an in vivo intradermal test.ResultsMajor allergen concentrations were 17.0 µg/mg (5.0 µg/mg of Der f 1 and 12.0 µg/mg of Der f 2) for a D. farinae extract and 24.0 µg/mg (11.6 µg/mg of Der p 1 and 12.4 µg/mg of Der p 2) for a D. pteronyssinus extract. Using chloramphenicol (CAP) inhibition assays, AUs were 12.5 AU/µg for a D. farinae extract and 12.8 AU/µg for a D. pteronyssinus extract. Allergenic activities were 3- to 4-fold stronger when assessed by intradermal skin tests for in vivo standardization.ConclusionsAllergen extracts were prepared from Korean house dust mites and the allergenicities of the extracts were estimated using AU measurements. House dust mite extracts prepared in this study could be utilized as a reference material, which will be useful for the development of diagnostic and immunotherapeutic reagents in Korea.

Efficacy and Safety of House Dust Mites Allergen Extracts Tablets in Adults With Allergic Rhinitis Patients

RATIONALE: Sublingual immunotherapy (SLIT) is well tolerated, and data suggest its effectiveness for house dust mites (HDM) adult allergic rhinitis treatment. We assessed the efficacy and safety of HDM SLIT tablets compared with placebo.

Stability evaluation of house dust mite vaccines for sublingual immunotherapy

Allergen-specific immunotherapy with house dust mite (HDM) allergen extracts can effectively alleviate the symptoms of allergic rhinitis and asthma. The efficacy of the immunotherapeutic treatment is highly dependent on the quality of house dust mite vaccines. This study was performed to assess the stability of house dust mite allergen vaccines prepared for sublingual immunotherapy. Lyophilized Dermatophagoides pteronyssinus (Dpt) mite bodies were the starting material for the production of sublingual vaccines in four therapeutic concentrations. The stability of the extract for vaccine production, which was stored below 4 ?C for one month, showed consistence in the protein profile in SDS PAGE. ELISA-inhibition showed that the potencies of Dpt vaccines during a 12 month period were to 65-80 % preserved at all analyzed therapeutic concentrations. This study showed that glycerinated Dpt vaccines stored at 4?C preserved their IgE-binding potential during a 12 month period, implying their suitability for sublingual immunotherapeutic treatment of HDM allergy.

Comparison and Evaluation of Several Dermatophagoides Pteronyssinus Allergen Extracts for Skin Prick Test

To evaluate the significance of several Dermatophagoides pteronyssinus allergen extracts for skin prick test (SPT) in patients allergic to Dermatophagoides pteronyssinus. Two hundred and nineteen patients enrolled in Peking Union Medical College Hospital underwent SPT and serum specific IgE assay to detect the Dermatophagoides pteronyssinus allergen. Three kinds of house dust mite allergen extracts were used for SPT, including the Dermatophagoides pteronyssinus extract prepared by our laboratory (group A), standardized Dermatophagoides pteronyssinus extract (group B), and mixed extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae (group C). Human serum specific IgE result was regarded as the reference standard for diagnosis of Dermatophagoides pteronyssinus allergy. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of SPT with the extracts of three groups. SPT results showed that the median wheal diameter of group A, group B, and group C was 0.43, 0.35, and 0.28 cm, respectively, with significant difference among three groups (P<0.05). The difference was significant between group A and B (P<0.01) as well as group A and C (P<0.01), but not between group B and C (P>0.05). There was no local urticaria or systemic allergic reactions following the procedure of SPT. Local reaction was observed in 5 patients and delayed reaction was in 2 patients of group A. As for group B and C, local reaction occurred in 3 cases and delayed reaction in 2 cases in each group. The area under ROC curve of SPT with extract in group A, group B, and group C was 0.765, 0.801, and 0.782, respectively. Based on the detection results of serum specific IgE, the sensitivity of SPT in diagnosis of Dermatophagoides pteronyssinus allergy with extract of group A, group B, and group C was 92.4%, 87.0%, and 81.5%, and the specificity was 60.6%, 73.2%, and 74.8%, respectively. The Dermatophagoides pteronyssinus extract for SPT prepared by our laboratory offers good sensitivity and specificity comparable to commercially available allergen extracts, and it may be an appropriate candidate for clinical screening and diagnosis of Dermatophagoides pteronyssinus allergy.

Use of A‐type CpG oligodeoxynucleotides as an adjuvant in allergen‐specific immunotherapy in humans: a phase I/IIa clinical trial

B-type CpG oligodeoxynucleotides (ODN) is currently used in clinical trials because of its prolonged half-life, which is due to its phosphorothioate backbone. A-type CpG ODN is a stronger inducer of IFN but has an unstable phosphodiester backbone that has so far prohibited its clinical use. However, upon association with virus-like particles (VLP) consisting of the bacteriophage Qbeta coat protein, A-type CpG ODN can be stabilized and can become an efficient adjuvant in mice. Therefore, the phase I/IIa study presented represents the first test of A-type CpGs in humans. To test the safety, tolerability and clinical efficacy of QbG10 as an adjuvant for subcutaneous immunotherapy with a house dust mite (HDM) allergen extract in allergic patients. A single centre, open-label phase I/IIa study evaluated the safety, tolerability and clinical efficacy of QbG10 as an adjuvant to immunotherapy with a subcutaneous HMD allergen extract in 20 patients suffering from HDM allergy. Twenty-one patients were enrolled between March and July 2005. Individual immunotherapy lasted 10 weeks. Clinical end-points included questionnaires, conjunctival provocation, skin prick tests and the measurement of allergen-specific IgG and IgE. QbG10 was well tolerated. Almost complete tolerance to the allergen was observed in conjunctival provocation testing after treatment with QbG10, and symptoms of rhinitis and allergic asthma were significantly reduced. Within 10 weeks of therapy, patients were nearly symptom-free and this amelioration lasted for at least 38 weeks post-treatment. Following injections of QbG10 and HDM allergen extract, allergen-specific IgG increased, while there was a transient increase in allergen-specific IgE titres. Skin reactivity to HDM was reduced. The subcutaneous application of HDM allergen, together with A-type CpG ODN packaged into VLP, was safe. All patients achieved practically complete alleviation of allergy symptoms after 10 weeks of immunotherapy. This promising clinical outcome calls for larger placebo-controlled phase II studies.

Effect of allergen-specific immunotherapy on plasma level of platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG), platelet activation markers in patients with house dust mite allergy

Patients suffering form house dust mite-sensitive persistent allergic rhinitis (PAR) seem to show changed platelet aggregability following mite allergen-specific immunotherapy (SIT). However, in patients with grass pollen-sensitive intermittent allergic rhinitis, platelet release reaction in vivo, measured by beta-TG, did not change significantly during the dose increase phase of subcutaneous SIT with grass pollen allergoids. The aim of this study was to evaluate the influence of SIT with house dust mite allergen extracts on the degree of circulating platelet activity in patients with PAR. The study comprised 14 patients sensitized to house dust mite allergens with PAR during the early phase of subcutaneous SIT with house dust mite allergen extracts— Dermatophagoides farinae 50 p.c. and Dermatophagoides pteronyssinus 50 p.c. (Novo-Helisen ® Depot, Allergopharma, Germany). SIT comprised subcutaneous injection of allergen extracts during approximately 3 months. Blood was collected before SIT, as well as immediately before, 30 min and 24 h after maximum dose injection. Plasma levels of PF-4 and beta-TG, platelet activation markers were measured using commercial ELISA kit. PF-4 and beta-TG basal levels were not significantly different between the patients and the healthy subjects. PAR patients treated with SIT showed no significant differences in plasma levels of the markers between the different points of the study. Thus, it seems that the degree of platelet activation measured by PF-4 and beta-TG does not change in PAR patients during hyposensitization with mite allergen extracts, after the maximum dose was reached.

Biochemical Characterization of Intact Allergen Extracts and Chemically Modified Allergoids Representing Grass, Birch and House Dust Mite Allergen Extracts

Biochemical Characterization of Intact Allergen Extracts and Chemically Modified Allergoids Representing Grass, Birch and House Dust Mite Allergen Extracts

Expression of CD163 on peripheral blood monocytes in allergic asthma patients during specific immunotherapy (SIT)

RATIONALE: CD163 is expressed on alternatively activated mononuclear phagocytes. The aim of this study was to evaluate the expression of CD163 and CD36 on peripheral blood monocytes of allergic asthma patients during SIT with house dust mite allergen extracts.METHODS: 25 mild allergic asthma (AA) patients with positive skin prick tests and a positive bronchial provocation test with Dermatophagoides pteronyssinus extract were selected for the study. 10 nonatopic healthy persons (HP) were used as a control group. SIT was performed on 20 (AA-IT) patients using Novo Helisen Depot. 5 patients (AA) who declined SIT were considered a control group. Blood was collected before, 3 months and 12 months after initiation of SIT. FACS analysis was performed on whole blood samples using labeled monoclonal antibodies against CD14, CD36 and CD163 (Pharmingen, USA).RESULTS: Before SIT more CD14 cells co-expressing CD163 (CD14+/CD163+) were found in AA-IT (47.4 +/- 19.6%) and AA (43.2 +/- 16%) than in HP (25.6 +/- 8.5; p< 0.01). In AA-IT patterns during SIT the number of CD14+/CD163+ cells increased reaching 54.8 +/- 11.6 % at 3 months and 49.1 +/- 8.9% at 12 months (p<0.01). The maximum increase in CD14+/CD163+ cells was associated with maximum improvement in FEV1. No change was found in the number of CD14+/CD163+ cells in AA during 12 month period. The number of CD14+/CD36+ monocytes decreased in AA-IT but did not change in AA.CONCLUSIONS: In house dust mite sensitive asthmatics, SIT is associated with alternative activation of peripheral blood monocytes. RATIONALE: CD163 is expressed on alternatively activated mononuclear phagocytes. The aim of this study was to evaluate the expression of CD163 and CD36 on peripheral blood monocytes of allergic asthma patients during SIT with house dust mite allergen extracts. METHODS: 25 mild allergic asthma (AA) patients with positive skin prick tests and a positive bronchial provocation test with Dermatophagoides pteronyssinus extract were selected for the study. 10 nonatopic healthy persons (HP) were used as a control group. SIT was performed on 20 (AA-IT) patients using Novo Helisen Depot. 5 patients (AA) who declined SIT were considered a control group. Blood was collected before, 3 months and 12 months after initiation of SIT. FACS analysis was performed on whole blood samples using labeled monoclonal antibodies against CD14, CD36 and CD163 (Pharmingen, USA). RESULTS: Before SIT more CD14 cells co-expressing CD163 (CD14+/CD163+) were found in AA-IT (47.4 +/- 19.6%) and AA (43.2 +/- 16%) than in HP (25.6 +/- 8.5; p< 0.01). In AA-IT patterns during SIT the number of CD14+/CD163+ cells increased reaching 54.8 +/- 11.6 % at 3 months and 49.1 +/- 8.9% at 12 months (p<0.01). The maximum increase in CD14+/CD163+ cells was associated with maximum improvement in FEV1. No change was found in the number of CD14+/CD163+ cells in AA during 12 month period. The number of CD14+/CD36+ monocytes decreased in AA-IT but did not change in AA. CONCLUSIONS: In house dust mite sensitive asthmatics, SIT is associated with alternative activation of peripheral blood monocytes.

Expression of selected surface proteins on peripheral blood monocytes of asthma patients treated with specific immunotherapy with house dust mite allergen extracts

Expression of selected surface proteins on peripheral blood monocytes of asthma patients treated with specific immunotherapy with house dust mite allergen extracts