House Dust Mite Specific Immunotherapy Research Articles

Molecular allergen IgE tests show neosensitizaions occurring during house dust mite specific immunotherapy

Objective:Neosensitizations may be occur during the allergen specific immunotherapy（AIT） due to the differences between allergen vaccine's content and a patient's molecular sensitization profile. This study investigates whether AIT with HDM extract changes the sensitization profile, whether de novo sensitization occurs, and the clinical importance of the neosensitization. Methods:Fifty-three patients with HDM allergic rhinitis ,with/without asthma, patients were received one year HDM subcutaneous AIT . Fourteen patients were recruited as control group and received only necessary medications. Serum samples were collected at baseline, 6thmoths and 12thof AIT, respectively. Serum samples were tested specific IgE against Der p, Der p 1/2/3 and Der f, Der f 1/2/3, as well as IgG4 against Der p, Der p 1/2 and Der f, Der f 1/2. VAS were collected at the time-points as well. Results:In AIT group, Der p, Der p 1/3, and Der f 1/3 specific IgE levels were significantly higher after one-year treatment, especially for Der p 3. There were 69.2%（18/26） patients whose Der p 3 specific IgE below 0.35 kU/L at baseline but became positive（>0.35 kU/L） after treatment, that is, neosensitization occurred. All tested allergen specific IgG4 level significantly increased after one year AIT treatment and the VAS declined dramatically. However, for patients with neosensitization and without neosensitization, there were no significantly changes concerning to IgG4 level and VAS. Conclusion:Patients undergoing AIT might have a risk of neosensitization to the allergen components in the vaccines. However, the clinical importance of the neosensitization remains unclear and warrants further studies.

House dust mite-specific immunotherapy alters the natural course of atopic march.

Allergen immunotherapy (AIT) is an effective treatment for patients with allergic diseases; it has been shown to modify the underlying cause of the disease. The house dust mite (HDM) is a major perennial allergen source and a significant cause of allergic-related diseases such as allergic rhinitis, asthma, and atopic dermatitis. HDM allergen is an important factor in the pathogenesis of allergic diseases. Sensitization to HDM allergen often occurs early in life and appears to play an important role in the progression from allergic rhinitis to asthma in children. The role of HDM AIT results in immunologic tolerance, provides an alternative option for treating HDM allergy through targeting the mechanisms of allergic reaction, and creates a long-term benefit. There are two forms of testing for aeroallergen, either detect by skin testing or by in vitro IgE assays. Both subcutaneous immunotherapy and sublingual immunotherapy are effective in the treatment of allergic diseases. In the future, new forms of allergen extracts can help improve safety and efficacy of AIT. Novel approaches to immunotherapy currently being explored include the use of adjuvants, allergen-derived peptides, modified recombinant allergen vaccines, and gene-specific immunotherapy.

Der p 1-specific regulatory T-cell response during house dust mite allergen immunotherapy.

Allergen-specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen-specific regulatory T (Treg) cells. We studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite-specific immunotherapy. Peripheral blood mononuclear cells were studied before and after 10, 30weeks, and 3years of AIT. Der p 1-specific T regulatory cell responses were investigated by characterization of Der p 1-MHC class II tetramer-positive cells and correlated with nasal symptom score. Twelve of 25 AIT patients matched with their MHC class II expression to the Der p 1 peptide-MHC class II tetramers. A significant increase in the numbers of Der p 1-specific FOXP3+ Helios+ CD25+ CD127- Treg cells after 30weeks was observed, which slightly decreased after 3years of AIT. In contrast, Der p 1-specific immunoglobulin-like transcript 3 (ILT3)+ CD25+ Treg cells decreased substantially from baseline after 3years of AIT. ILT3+ Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1-specific IL-10 and IL-22 responses have increased after 30weeks, but only IL-10+ Der p 1-specific Treg cells remained present at high frequency after 3years of AIT. Increased number of FOXP3+ Helios+ and IL-10+ and decreased ILT3+ Treg cell responses correlated with improved allergic symptoms. The results indicate that AIT involves upregulation of the activated allergen-specific Treg cells and downregulation of dysfunctional allergen-specific Treg cell subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response.

Role of Der p 1–specific B cells in immune tolerance during 2 years of house dust mite–specific immunotherapy

Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported. Allergen-specific B-cell responses during 2years of house dust mite AIT were compared between responder and nonresponder patients. B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequency of IgA-, IgG1- and IgG4-switched Der p 1-specific B cells, plasmablasts, and IL-10- and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT. Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23±0.28 to 2.45±0.24 (P=.001) and a decrease in skin prick test reactivity to house dust mite from 7.0±1.3 to 2.7±0.5mm(P=.001). IgG4+ and IgA+ Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG4+ but not the IgA+ fraction. The frequency of plasmablasts and IL-10- and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2years. The increased frequency of Der p 1-specific IgG4+ B cells, plasmablasts, and IL-10+ and dual-positive IL-10+IL-1RA+ Breg cells significantly correlated with improved clinical symptoms over the course of AIT. Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA- and IgG4-expressing Der p 1-specific B cells, plasmablasts, and IL-10+ and/or IL-1RA+ Breg cells.

Retrospective Analysis on the Effects of House Dust Mite Specific Immunotherapy for More Than 3 Years in Atopic Dermatitis.

PurposeIn extrinsic atopic dermatitis (AD), house dust mites (HDM) play a role in eliciting or aggravating allergic lesions. The nature of skin inflammation in AD has raised a growing interest in allergen-specific immunotherapy (SIT). Thus, we assessed clinical improvement and laboratory parameters for evaluation of the benefit of long-term SIT.Materials and MethodsA total of 217 AD patients who were treated with SIT for at least 3 years were retrospectively assessed, by using their investigator global assessment, pruritus scores, loss of sleep (LOS), total serum IgE, and eosinophil counts collected. Patients were additionally classified into subgroups according to age, initial AD severity and mono- or multi-sensitization to include different individual factors in the evaluation of SIT efficacy. Lastly, we compared laboratory data of good responders to SIT with that of poor responders to SIT.ResultsImprovement after SIT therapy was observed in 192 out of 217 patients (88.4%). Among these patients, 138 (63.5%) achieved excellent, near-complete or complete clinical remission. Significant reduction of pruritus, LOS, and the mean value of total serum IgE were observed (p<0.01). Better outcome was found in patients younger than 12 years of age (p=0.024). Patients with moderate to severe AD showed better treatment outcomes (p=0.036). Patients sensitized only to HDM had the better response to treatment, but SIT was also effective in multi-sensitized groups (p=1.051). No significant differences in baseline laboratory results were observed between good and poor responders (p>0.05).ConclusionWe emphasize the usefulness of long-term HDM SIT as a disease-modifying therapy for AD.

House dust mite-specific immunotherapy and tropomyosin sensitizations: harm or benefit for patients?

Background Allergenic tropomyosins are highly cross-reactive panallergens found in various invertebrates. Sensitized patients can develop allergic responses ranging from oral allergy syndrome to severe anaphylactic reactions after the ingestion of tropomyosin-containing food. The usual routs of sensitization to tropomyosin include the airborne exposure to various mites and cockroaches and the oral intake of crustaceans and mollusks. There were also reports of patients with combined mite and seafood allergy who had experienced a worsening of food allergy symptoms during house dust mite-specific immunotherapy (HDM-SCIT). Therefore, a possibility that mite tropomyosin present in allergen extracts can cross-sensitize patients receiving HDM-SCIT and thus induce food allergy is still investigated.Our aim was to assess the occurrence and the clinical relevance of tropomyosin sensitizations in HDM-SCIT-treated patients.

Efficacy of house dust mite–specific immunotherapy in patients with atopic dermatitis

Efficacy of house dust mite–specific immunotherapy in patients with atopic dermatitis

Transforming growth factor-beta1 and IL-13 response to allergen predict steroid needs in asthmatic children

BackgroundThe remission of asthma, which is induced during specific immunotherapy (SIT) or appears spontaneously in children is not completely understood and predictors of this phenomenon are still undefined. ObjectiveTo assess CD4+CD25+Foxp3+ Treg cells and cytokine/proliferation response to allergen-specific stimulation of PBMC as predictors of steroid sparing effect of SIT and steroid dosage needs without SIT during 5 years of follow-up in asthmatic children. MethodsThis is a 5-year long study of 32 asthmatic children, sensitive only to house dust mite (HDM). Eighteen children who had completed 5 years of HDM SIT – SIT group, and 14 children without SIT as a control group were studied. All patients had baseline clinical/immunological assessment; before and after observation the minimum effective ICS dose was defined and lung function was measured. ResultsIn children from SIT group minimum effective ICS dose was reduced more than in children from control group (median reduction 65% vs. 0%; p<0.001). Among patients in control group asthma severity was reduced after 5 years of observation in those who had at baseline higher TGF-beta1 and lower IL-13 answer to allergen stimulation of PBMC. Better response to 5 years immunotherapy was observed in those who had at baseline higher TGF-beta1 and lower proliferation answer to allergen stimulation of PBMC. ConclusionSimilar processes may decide on both, SIT-induced and spontaneously appearing, reduction in asthma severity. Immunotherapy was much more effective than pharmacotherapy in our study. IL-13 overproduction may impede reduction of disease severity in asthmatic children independently from TGF-beta pathway.

The role of S100A8/A9, a DAMP - mediated inflammation in atopic dermatitis

S100A8/A9 (Calprotectin) is a member of 2 EF-hand Ca2+ binding family protein. It is called “damage-associated molecular pattern (DAMP)” molecule because of its pro-inflammatory role in acute and chronic inflammation. Previously we used proteomics methods and found that S100A8/A9 was significantly down regulated after house dust mite specific immunotherapy in AD patients. Forty-five patients with mild to severe AD and twenty non-atopic individuals were recruited to analyze serum levels of S100A8/A9.

Comparison of the long-term efficacy of 3- and 5-year house dust mite allergen immunotherapy

BackgroundThe recommended duration of specific immunotherapy (SIT) treatment relies on empiric data and is not well documented. ObjectiveTo detect possible differences in the long-term effectiveness between 3 and 5 years of house dust mite (HDM) SIT in asthmatic children. MethodsWe performed a 3-year natural history study of 90 asthmatic children who were sensitive only to HDM. Three groups were recruited: 30 who had completed 3 years of HDM SIT (SIT3), 30 who had completed 5 years of HDM SIT (SIT5), and 30 who had an indication for HDM SIT but whose parents refused HDM SIT. Patients attended an enrollment visit in 2007, after SIT discontinuation, and 3 annual follow-up visits at the clinic. The long-term effectiveness of HDM SIT was primarily assessed via analysis of the reduction in required inhaled corticosteroid dose, forced expiratory volume in 1 second, and asthma remission. ResultsA total of 84 children completed the study. Both SIT durations produced excellent results; asthma remission in both SIT3 (50%) and SIT5 (54%) groups was significantly higher when compared with control (3.3%). The minimal controlling inhaled corticosteroid dose reduction in SIT5 group (median, 75%) was significantly higher compared with the SIT3 group (median, 50%) after immunotherapy discontinuation; after 3 years without SIT, no differences were found between the SIT5 and SIT3 groups (median, 100% and 94%, respectively). We observed a slightly higher increase in forced expiratory volume in 1 second in the SIT5 group compared with the SIT3 group. ConclusionThree years of SIT is an adequate duration for the treatment of childhood asthma associated with HDM allergy because 2 further years of SIT added no clinical benefit.

House Dust Mite-Specific Immunotherapy Alters the Basal Expression of T Regulatory and FcεRI Pathway Genes

Background: Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Methods: Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG₄, nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Results: Decreased wheal sizes and VAS scores, negative challenges and increased sIgG₄ levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Conclusions: Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal expression of FOXP3.

Subcutaneous Immunotherapy with a Depigmented Polymerized Birch Pollen Extract – A New Therapeutic Option for Patients with Atopic Dermatitis

Background: Birch pollen is an important outdoor allergen able to aggravate symptoms in atopic dermatitis (AD). Specific immunotherapy (SIT), an established procedure for allergic airway diseases, might also represent an attractive therapeutic option for the causal treatment of allergen-triggered cutaneous symptoms in these patients. Studies with house dust mite SIT have already shown beneficial effects in AD patients, whereas the safety and efficacy of SIT with birch pollen extract in AD patients have not been studied so far. The aim of this study was to evaluate for the first time the safety and efficacy of SIT with a depigmented polymerized birch pollen extract in AD patients. Methods: Fifty-five adult patients with moderate-to-severe AD and clinically relevant sensitization to birch pollen received SIT for 12 weeks. SIT was continued during birch pollen season. The assessment of safety, the total SCORAD value, and the Dermatology Life Quality Index (DLQI) were evaluated. Results: The median total SCORAD value was reduced by 34% (p < 0.001) during the course of treatment and the mean DLQI improved by 49% (p < 0.001) despite strong simultaneous birch pollen exposure. Eight patients (14.5%) developed systemic reactions and 19 patients (34.5%) developed local reactions which were of mild intensity in most cases. No patient discontinued the study prematurely due to adverse drug reactions. Coseasonal treatment was well tolerated. Conclusion: SIT with a depigmented polymerized birch pollen extract leads to significant improvement of the SCORAD value and the DLQI in patients suffering from moderate-to-severe AD sensitized to birch pollen.

Clinical Efficacy of House Dust Mite-specific Immunotherapy in Asthmatic Children

Immunotherapy has been widely used in the treatment of allergic diseases. We evaluated the clinical efficacy of specific immunotherapy with extracts of Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df) in children with asthma. All 40 children had moderate-to-severe asthma and positive allergen tests for Dp and Df. All required daily medication. They were randomly assigned to two groups: Half of them received immunotherapy with subcutaneous injections of Dp and Df extracts, while the other half were not given immunotherapy. Participants were followed up for more than 6 months. Children in both groups had apparent improvements in medication use and symptoms after 6 months. The mean medication scores declined from 3.6 +/- 1.14 to 1.7 +/- 0.66 in the immunotherapy group (p < 0.01) and from 3.35 +/- 0.87 to 2.4 +/- 1.09 in the control group (p < 0.01). There was a significant difference between the two groups (mean difference 0.95; p < 0.01). The symptom score improved in the immunotherapy group from 2.65 +/- 0.98 to 1.20 +/- 1.00 (p < 0.01) and in the control group from 2.55 +/- 0.99 to 1.40 +/- 0.88 (p < 0.01), with a significant difference between the two groups (mean difference 0.3; p < 0.01). The number of office visits in the immunotherapy group was greater than that of the controls, but the frequencies of emergency room visits and hospitalization decreased. Our study showed that specific immunotherapy with Dp and Df was beneficial for asthmatic children.

Changes in the Levels of D. farinae Specific IgE, IgG 4 and Their Immunoblotting Patterns After the Long-term House Dust Mite Specific Immunotherapy

Changes in the Levels of D. farinae Specific IgE, IgG 4 and Their Immunoblotting Patterns After the Long-term House Dust Mite Specific Immunotherapy

Lack of de novo Sensitization to Tropomyosin in a Group of Mite-Allergic Patients Treated by House Dust Mite-Specific Immunotherapy

Background: There is some evidence that specific immunotherapy may induce de novo sensitization to proteins contained in the allergen extract. This raises the possibility that the novel sensitization to cross-reacting allergens may cause food allergies. Objective: The aim of this study was to assess whether injection of mite-specific immunotherapy (SIT) may induce sensitization to shrimp tropomyosin. Methods: Seventy mite-allergic subjects who did not show any shrimp sensitization at baseline were followed up for at least 3 years. Thirty-one of them underwent a 3-year SIT course, 39 served as controls. At the follow-up visit, SPTs with both fresh shrimp and commercial extract were performed, and patients underwent an open oral challenge with shrimp. Results: Neither patient nor control had become sensitized to shrimp allergens at the end of the study period. Both patients and controls reported the regular intake of crustaceans and/or molluscs. Conclusion: Injection SIT with house dust mite extracts does not seem to induce de novo tropomyosin sensitization in mite-allergic patients.

Inmunoterapia con un extracto de ácaros en niños menores de cinco años

Specific immunotherapy with allergens is the only treatment capacite of modifying the natural course of allergic diseases. Although its effectiveness is higher when started in early stages, WHO guidelines still consider age under 5 years as relative contraindication.A review of a group of 22 children starting immunotherapy before the age of 5 years in a pediatric allergy unit was attempted to assess the effectiveness and safety of this treatment. Clinical charts of 22 children with house dust mite asthma starting conventional immunotherapy before the age of 5 years were reviewed. In all cases, biologically standardized extracts and conventional subcutaneous schedules have been used and administration was performed in a hospital setting. Effectiveness and safety were evaluated by clinical scores. The average treatment period was 16.95 ( 10.12) months. Systemic reactions (moderate) were observed in 7 children and local reactions in 5. Children treated for more than 1 year (15 patients) showed a decrease in the number of yearly acute exacerbations (from 5.13 to 2.57) and in hospital admissions (from 5 to 2 children). In 10 patients, drug requirements for bronchial asthma were reduced. The clinical data if this study suggest that house dust mite specific immunotherapy under hospital control can be begun in young children with good tolerance and clinical improvement.