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M van Hage-Hamsten

Publications and source records attributed to M van Hage-Hamsten.

At least 19 recordsLinked to original sources

Skin prick test and serological analysis with recombinant group 2 allergens of the dust mites L. destructor and T. putrescentiae.

BACKGROUND: The dust mites Lepidoglyphus destructor and Tyrophagus putrescentiae are important sources of allergen in farming environments. The major allergens of the dust mites L. destructor and T. putrescentiae have been cloned and expressed as recombinant proteins. OBJECTIVE: To evaluate the use of recombinant group 2 allergens of L. destructor (rLep d 2) and T. putrescentiae (rTyr p 2) in skin prick test (SPT), and serological analysis in sensitized and non-sensitized farmers chronically exposed to dust mites. METHODS: Skin prick test with rLep d 2, rTyr p 2 and the corresponding commercial extracts was performed in 44 farmers sensitized to L. destructor and/or T. putrescentiae, and 38 control farmers. IgE and IgG subclass antibodies to the recombinant allergens were analysed by RAST and ELISA, respectively. RESULTS: Out of the 44 subjects positive in SPT to L. destructor and/or T. putrescentiae extract, 26 (59%) displayed a positive SPT to one or the other of the recombinant allergens, whereas 21 (48%) were positive to both. Significant correlations were registered between the sizes of the weals induced by rLep d 2 and rTyr p 2 and the corresponding RAST values (P < 0.001). A majority of subjects positive in SPT to the recombinant allergens had detectable IgG4 antibodies, and the levels were significantly higher in the dust mite sensitized group than in the controls (P < 0.05). No such differences were found in the IgG1 values (P > 0.05). The results obtained with rLep d 2 and rTyr p 2 correlated relatively well with each other with respect to SPT, RAST and IgG4, suggesting that the allergens have similar or shared IgE epitopes. All the control subjects had a negative SPT and RAST to rLep d 2 and rTyr p 2. CONCLUSION: Recombinant group 2 allergens from the dust mite L. destructor and T. putrescentiae represent useful tools for diagnosis of dust mite allergy.

Adult↗

Skin test evaluation of genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1: results obtained with a mix of two recombinant Bet v 1 fragments and recombinant Bet v 1 trimer in a Swedish population before the birch pollen season.

BACKGROUND: More than 95% of birch pollen-allergic subjects react with the major birch pollen allergen, Bet v 1, and almost 60% of them are sensitized exclusively to this allergen. OBJECTIVE: The aim of this study was to compare the in vivo biologic activity of genetically engineered hypoallergenic derivatives of Bet v 1 (an equimolar mixture of 2 recombinant [r] Bet v 1 fragments and of rBet v 1 trimer) with that of rBet v 1 wild-type by skin prick and intradermal testing. METHODS: Birch pollen-allergic patients who had not received immunotherapy (n = 23), a group of allergic patients without birch pollen allergy (n = 12), and nonatopic persons (n = 8) from northern Europe (Sweden) underwent skin prick and intradermal testing with different concentrations of the recombinant allergens and commercial birch pollen extract before the birch pollen season. Immediate and late-phase reactions were recorded and allergen-specific IgE and IgG subclass responses were determined by CAP radioallergosorbent test and ELISA, respectively. RESULTS: Atopic persons without birch pollen allergy and nonatopic individuals did not have skin reactions to rBet v 1 wild-type and genetically engineered hypoallergenic derivatives. By intradermal testing, 8 of 23 and 13 of 23 birch pollen-allergic patients did not react with the highest concentration (1 microg/mL) of the rBet v 1 fragment mix and rBet v 1 trimer, respectively, compared with 1 with rBet v 1 wild type. Likewise, the highest concentration (100 microg/mL) of fragment mix or trimer failed to elicit a positive skin prick test in 18 of 23 and 15 of 23 patients in comparison with 0/23 with the monomer. No late reactions were observed. CONCLUSION: The recombinant hypoallergenic birch pollen allergens can probably be used for patient-tailored immunotherapy with a reduced risk to induce anaphylactic reactions.

Adolescent↗

Influence of interaction of environmental risk factors and sensitization in young asthmatic children.

BACKGROUND: The increasing prevalence of asthma and allergy in many countries demands evaluation of potential risk factors to improve the possibility of prevention. OBJECTIVE: We studied the association between exposure to cat and dog allergen and allergic sensitization in young children with asthma and interactions with potential environmental risk factors. METHODS: One hundred eighty-nine young children with asthma were evaluated. IgE antibodies to cat and dog were analyzed. Questionnaires were filled in focusing on exposure to cats and dogs, environmental tobacco smoke (ETS), and signs of home dampness as indicated by window pane condensation (WPC) during the first years of life. House dust was analyzed for content of cat (Fel d 1) and dog (Can f 1) allergen. RESULTS: There was a strong association between the degree of reported exposure to cat and dog and the concentration of the respective allergens in floor dust. A dose-response relationship was found between cat exposure, measured as either reported degree of cat exposure or cat allergen levels in dust, and sensitization both to cat and dog. No such relationship was found between exposure and sensitization to dog. WPC increased the risk for sensitization to cat (odds ratio = 2.6, 95% confidence interval 1.2-5.8), whereas ETS strongly tended to do so both to cat and dog. Interaction was found between exposure to ETS, WPC, and high levels of cat allergen (>8 microg/g dust). The presence of all 3 risk factors revealed a multiplicative interaction with a high risk of sensitization to cat (odds ratio = 42.0, 95% confidence interval 3.7-472.8). CONCLUSIONS: Keeping cats indoors may be a health hazard for infants and young children at risk for development of asthma, particularly when they live in a damp house and their parents smoke.

Allergens↗

Sensitization to allergens of house-dust mite in adults with atopic dermatitis in a cold temperature region.

BACKGROUND: An IgE-mediated contact reaction to airborne allergens has been suggested as one important pathogenetic mechanism in atopic dermatitis (AD). The house-dust mite (HDM) might be a common allergen involved. In Scandinavia, sensitization to HDM has been rare, probably because of the cold, dry climate. However, recent studies indicate high levels of domestic mites and HDM allergen in 15-20% of homes in central and northern Sweden. METHODS: To evaluate the importance of the HDM in patients with AD in the Stockholm region, we screened 81 adult Stockholm residents with AD, for the prevalence and degree of sensitization to the HDM, according to specific IgE (RAST), skin prick test (SPT), and atopy patch test (APT). We also assessed the HDM exposure in their homes and correlated the results with clinical history, severity of the dermatitis, and type of residence during childhood and today. RESULTS: The sensitization rate to HDM was high (56% according to RAST, 24% according to SPT, and 47% according to APT), and 20% of the patients were exposed to HDM allergens in their beds. Mite exposure seemed to aggravate the dermatitis in highly sensitized patients. CONCLUSIONS: The results indicate that we have to take the HDM into account when discussing aggravating factors in adult patients with AD in the Stockholm region.

Adolescent↗

Risk factors associated with asthma and rhinoconjunctivitis among Swedish farmers.

BACKGROUND: Earlier studies have shown a high prevalence of respiratory symptoms in farming communities and that storage mites constitute important allergens. We examined risk factors associated with asthma and rhinoconjunctivitis among Swedish farmers. METHODS: A population of 1015 small-scale dairy farmers was part of an epidemiologic survey. After selection based on symptom reports in a questionnaire, 461 of the farmers attended a medical examination, which comprised SPT, RAST analyses, and lung-function measurements. Risk factors for sensitization to different allergens, and development of asthma and rhinoconjunctivitis were assessed by multiple logistic regression. RESULTS: The prevalence of atopy was 26.7% among the farmers. For both asthma and rhinoconjunctivitis, sensitization to mites (OR = 5.8 vs. OR = 3.8) and pollens (OR = 10.3 vs. OR=5.8) was a significant risk factor. There was a significant relationship between sensitization to mites and working time (OR = 5.2). Environmental tobacco smoke and exposure to different animal species at the farm did not appear to affect the risk of allergen sensitization or respiratory symptoms. Farmers smoked less than the general population, but they more frequently had reduced FEV1. CONCLUSIONS: Allergen sensitization, especially to mites and pollens, was significantly associated with asthma and rhinoconjunctivitis in a farming community. The results point to allergen avoidance as a major goal for the prevention of occupational respiratory diseases among the farming population.

Adolescent↗

Exposure to an abundance of cat (Fel d 1) and dog (Can f 1) allergens in Swedish farming households.

BACKGROUND: Earlier studies have shown that farmers are to a low degree sensitized to animal allergens. We have measured the amount of cat (Fel d 1) and dog (Can f 1) in farm households and examined the relationship between exposure and sensitization to cat and dog allergens. METHODS: Dust samples from the homes of 403 farmers who had participated in an epidemiologic follow-up study on respiratory symptoms were analyzed for allergen content by two-site ELISA methods. RESULTS: Fel d 1 was detected in 99.5% of the farmers' households ranging from 0.055 to 1455 microg/g dust in mattresses (GM 13.2) and to 3775 microg/g dust in living-room carpets (GM 17.1). Can f 1 was detected in 90.6% of the households from 0.2 to 116 microg/g dust in mattresses (GM 2.0) and to 504 microg/g dust in carpets (GM 4.3). Homes with pets present had the highest levels of the allergens (P<0.001). A total of 8.4% and 7.4% of the farmers were sensitized to cat and dog, respectively. A significant correlation was noted between exposure to the allergens and specific IgE to cat and dog, respectively (P<0.001). Sensitization to cat (OR = 4.9) and dog (OR = 17.8) was significantly associated with asthma. CONCLUSIONS: In spite of the abundance of Fel d 1 and Can f 1, farmers are only to a low degree sensitized to cats and dogs.

Agricultural Workers' Diseases↗

Markers of inflammation and bronchial reactivity in children with asthma, exposed to animal dander in school dust.

Several studies have confirmed the presence of animal dander allergens in school dust but the effect of this indirect animal exposure on health has not been evaluated. In this study we investigated bronchial reactivity and markers of eosinophil activity and inflammation during two separate weeks of school in 10 children with mild asthma and a positive skin prick test to cat and dog. At the beginning and the end of the first week the children underwent bronchial challenges with methacholine, and at the beginning and the end of the second week they underwent nasal lavages (NAL) and induced sputum samplings. Blood and urine samples for analysis of inflammatory markers were obtained before and after both school weeks. Peak expiratory flow (PEF) and symptoms of asthma and allergy were recorded daily, and spirometry was performed on each visit. The exposure to animal dander allergens was estimated from dust samples obtained in the subjects' schools and homes. Bronchial sensitivity to methacholine increased in the week when this was measured. The proportion of eosinophils in peripheral blood, and urinary eosinophil protein X (EPX), decreased in both weeks. There was a trend towards an increase of eosinophil peroxidase (EPO) and myeloperoxidase (MPO) in sputum in the week when these proteins were measured. The concentrations of cat (Fel d1) and dog (Can f1) allergens were higher in dust collected in schools than in homes. Our results show that in children with mild asthma and animal dander allergy, there is a significantly increased bronchial sensitivity to methacholine after one school week. There is also a significant decrease in the number of circulating eosinophils and a trend towards an increase of sputum EPO, which could correlate with the early phase of eosinophil recruitment to the lungs. These effects may be related to the continuous exposure to animal allergens in school dust.

Adolescent↗

Vernal keratoconjunctivitis in a Stockholm ophthalmic centre--epidemiological, functional, and immunologic investigations.

PURPOSE: To classify a cohort of 62 patients with vernal keratoconjunctivitis (VKC) in immunologic, functional, and epidemiological terms. METHODS: A retrospective chart review was conducted to establish the patients' ethnic origin and to ascertain the results of standard in vitro and in vivo testing for atopic allergy. The latter data were compared with tear Phadiatop, an allergy screening test, in 31 subjects. Further subgroup analyses included methacholine bronchial provocations, serum screening for chlamydial antibodies and epidemiological calculations of the observed prevalence of VKC in the Stockholm area in 1994. RESULTS: Thirty-seven subjects (59.7%) were sensitised to common allergens. No additional allergic subjects were diagnosed with the tear Phadiatop test. The serology for ocular chlamydial disease was negative. Only 6 out of 17 subjects displayed bronchial reactivity to methacholine of whom 4 had a history of asthma. VKC was clearly more common in individuals with an Asian and African origin. CONCLUSIONS: Sensitivity to allergens is a strong determinant for the disease but in a large proportion of the subjects this immunologic abnormality is absent. The varying prevalence of the condition in different ethnic groups indicates a genetic predisposing factor.

Adolescent↗

Increasing prevalence of asthma over 12 years among dairy farmers on Gotland, Sweden: storage mites remain dominant allergens.

BACKGROUND: Earlier studies from several countries have shown that IgE-mediated allergy in rural populations is of considerable importance and that storage mites are dominant allergens. OBJECTIVE: In an epidemiological follow-up study among farmers on the island of Gotland, Sweden in 1996 we wished to investigate the prevalence of respiratory allergy and to find out whether storage mites are still important allergens in a farming environment. METHODS: A questionnaire concerning airway symptoms, social and working conditions and smoking habits was distributed to all Gotland farmers aged 15-65 years and was completed by 1577 (86.7%), of whom 1015 were dairy farmers. Based on the answers, 500 dairy farmers were invited to undergo a medical examination which included a skin-prick test (SPT) and blood sampling for RAST analyses. Prevalence figures (symptoms, RAST and SPT) given for the whole population (n = 1015) were based on the investigation of the 461 farmers who took part in the examination. RESULTS: Immediate onset hypersensitivity was present in 41.7% of the 1015 farmers studied, which is almost the same figure as in 1984 (40.0%). The prevalence of asthma had increased significantly during the previous 12 years (5.3% vs 9.8%), as had asthma in combination with rhinoconjunctivitis (3.7% vs 7.0%). Rhinoconjunctivitis, on the other hand, had not changed significantly (36.5% vs 33.1%) and remained one of the most common symptoms. The prevalence of storage mite allergy in the farming population in 1996 was 6.5% and constituted an important cause of allergic symptoms. CONCLUSION: Over 12 years, Gotland dairy farmers have developed significantly more respiratory symptoms from the lower airways, although the proportion with atopy is unchanged. Storage mites are still dominant allergens for developing allergic disease.

Adolescent↗

Characterization of eosinophils and detection of eotaxin in skin chamber fluid after challenge with relevant allergen in patients with mild asthma.

BACKGROUND: A selective recruitment of eosinophils to sites of allergic inflammation is suggested to be controlled by regulation of cytokines, chemokines and adhesion molecules. OBJECTIVE: The aim of this study was to examine whether allergen challenge in skin chambers, applied on patients with allergic rhinitis and mild asthma, results in a selective influx of activated eosinophils and detectable levels of cytokines/chemokines related to eosinophil recruitment, such as interleukin (IL)-5 and eotaxin. METHODS: A skin blister was induced on the volar aspect of each forearm; one contained PBS-heparin buffer (control) and the other was challenged with relevant allergen. Peripheral blood was drawn before the allergen was applied to the skin chamber, and the expression of CD9, CD11b and EG2-epitope on intracellular eosinophil cationic protein (ECP) was analysed in eosinophils. Chamber fluid was collected 8 h after allergen application and analysed for differential cell counts, expression of eosinophil activity markers, the presence of ECP, eotaxin, and IL-5. RESULTS: The number of recruited leucocytes was equal in the allergen-challenged chambers and in controls. However, the number of eosinophils was significantly increased in the allergen-challenged chambers, and elevated levels of released ECP were measured. Moreover, the eosinophils recruited were activated, as shown by increased expression of EG2 and CD11b, and decreased expression of CD9, in comparison with blood eosinophils. In the skin chamber fluids, higher levels of eotaxin were detected in the allergen-challenged chambers than in controls, but there were no detectable levels of IL-5. CONCLUSION: We have demonstrated a selective recruitment of eosinophils, and higher levels of released ECP and eotaxin, in skin chambers stimulated with allergen, as compared with control chambers. Allergen challenge in skin chambers is a useful tool for studies of eosinophil recruitment, their state of activation, and their involvement in the allergic inflammatory response.

Adult↗

Identification and characterisation of two allergens from the dust mite Acarus siro, homologous with fatty acid-binding proteins.

BACKGROUND: Dust mites are a major cause of allergic disease worldwide. The dust mite Acarus siro is an inducer of occupational allergy among farmers, but sensitisation has also been found in non-farming populations. METHODS: A degenerate primer was designed to the N-terminal amino acid sequence of a 15-kD IgE-binding protein in A. siro extract. The cDNA sequence was obtained by using reverse transcriptase polymerase chain reaction, standard cloning and sequencing techniques. The protein was expressed in Escherichia coli with a 6-histidine tag at its C-terminus. Immunoblotting of the recombinant protein and whole extract was performed using patient sera. RESULTS AND CONCLUSION: 15 and 17-kD allergens were identified in a fraction of A. siro extract. The cDNA of the 15-kD allergen was isolated, cloned and sequenced and the allergen was expressed as a recombinant protein. The calculated molecular weight of the cDNA-encoded protein is 14.2 kD. The predicted amino acid sequence has one potential N-glycosylation site at position 4-6 and a cytosolic fatty acid-binding protein signature at position 5-22. The protein has 64% sequence identity with Blo t 13, an allergen from the dust mite Blomia tropicalis, as well as homology with several other fatty acid-binding proteins (FABPs) from different organisms. The allergen was named Aca s 13 and was recognised strongly by 3 of 13 (23%) of the subjects investigated. The amino acid sequence of the 17-kD protein was partly determined and it also showed high sequence homology with Blo t 13 and FABPs.

Allergens↗

Evaluation of specific IgE to the recombinant group 2 mite allergens Lep d 2 and Tyr p 2 in the Pharmacia CAP system.

BACKGROUND: Several recombinant allergens have been shown to be potentially useful for diagnosis of IgE-mediated allergy, but only a few recombinant allergens are at present commercially available in serological assays for detection of specific IgE. The aim of this study was to evaluate the IgE binding to the recombinant major dust mite allergens rLep d 2 and rTyr p 2 and compare it with the IgE binding to the commercial mite extracts Lepidoglyphus destructor and Tyrophagus putrescentiae in the Pharmacia RAST CAP System. METHODS: The recombinant allergens rLep d 2 and rTyr p 2 were immobilised on ImmunoCAPs, and sera from 461 Swedish farmers who are frequently exposed to mites were analysed for specific IgE antibodies. Immunoblotting was performed to evaluate discrepancies between the results obtained with the recombinant and the commercial CAP assays. RESULTS: The IgE values of each recombinant assay significantly correlated with the IgE values of the corresponding commercial CAP assay. The sensitivity of the rLep d 2 assay was 73.3% and that of the rTyr p 2 assay, 60.5% of that provided by the commercial L. destructor and T. putrescentiae assays. Two subjects out of 416, who tested negative in the commercial L. destructor assay, were positive to rLep d 2. The corresponding figures for rTyr p 2 and the T. putrescentiae extract were 5/418. The possibility that these subjects were sensitised to L. destructor and T. putrescentiae could not be excluded. CONCLUSIONS: The data suggest that it may be possible to use rLep d 2 and rTyr p 2 on ImmunoCAPs to detect and quantify IgE antibodies to these, the major allergens of L. destructor and T. putrescentiae. It appears likely that the addition of just a few more recombinant L. destructor and T. putrescentiae allergens in the CAP assay will be sufficient for in vitro diagnosis of IgE mediated allergy to L. destructor and T. putrescentiae.

Allergens↗

Allergen-induced accumulation of eosinophils and lymphocytes in skin chambers is associated with increased levels of interleukin-4 and sVCAM-1.

BACKGROUND: The aim of the study was to characterize the kinetic accumulation of various inflammatory mediators in allergen-challenged skin chambers applied on patients with pollen-related allergic rhinitis/mild asthma. METHODS: Skin blisters were induced on the forearms and challenged with allergen or phosphate-buffered saline (PBS). Peripheral blood was drawn before and 8 h after challenge for analysis of differential cell counts, sVCAM-1, and alpha2-macroglobulin. Chamber fluids, collected at 1, 4, and 8 h after allergen application, were analyzed for differential cell counts, histamine, interleukin (IL)-4, sVCAM-1, and alpha2-macroglobulin. RESULTS: The number of recruited leukocytes was equal in allergen and PBS chambers; however, the numbers of eosinophils and lymphocytes were significantly (P< or =0.05) elevated in allergen-challenged chambers at 8 h. Compared to PBS chambers, allergen chambers contained significantly (P<0.01-0.05) higher levels of histamine (at 1 and 4 h), IL-4 (at 4 and 8 h), alpha2-macroglobulin (at 1 and 8 h), and sVCAM-1 (at 1 and 8 h). In contrast to alpha2-macroglobulin, levels of sVCAM-1 in peripheral blood were significantly (P<0.05) increased at 8 h. CONCLUSIONS: Increased levels of sVCAM-1 and IL-4 in allergen-challenged chambers, in parallel with increased recruitment of eosinophils and lymphocytes, points to the participation of IL-4 and VCAM-1 in the development of the late-phase reaction. Increased levels of sVCAM-1 in allergen-challenged chambers probably reflects a combination of leakage and local production.

Adult↗

beta-Tryptase measurements post-mortem in anaphylactic deaths and in controls.

The reliability of measuring mast cell tryptase in post-mortem blood to diagnose anaphylactic deaths has been questioned because moderate elevation of tryptase can be seen also in control cases. Very high tryptase concentrations have been recorded even in a few control cases with known cause of death such as myocardial infarction or trauma. Aiming to compare findings we measured tryptase in 193 cases: 176 with known cause of death, 10 unexplained deaths and seven anaphylactic or anaphylactoid deaths (AADs). Using binary logistic regression we calculated the sensitivity and specificity of the tryptase test at different cut-off values and found 10 micrograms/l to be optimal, the sensitivity being 86% and the specificity 88%. Traumatic deaths (n = 23), sudden infant death syndrome (n = 40) or deaths after heroin-injection (n = 22) showed elevated tryptase values in 35%, 35% and 32%, respectively, and in 40% of the unexplained deaths (n = 10), which was higher than expected (12%). Heart blood tryptase level was elevated in 22% of the controls and femoral blood tryptase in 10%. No correlations were seen with age or post-mortem delay. It is concluded that tryptase measurements are useful in confirming death from AAD, and that blood should be sampled from the femoral vessels. In unexplained deaths tryptase measurement is a useful indicator, but the diagnosis is not to be based on the test alone.

Adult↗

Cloning and characterisation of a group II allergen from the dust mite Tyrophagus putrescentiae.

The complete cDNA encoding a major allergen from the dust mite Tyrophagus putrescentiae, Tyr p 2, has been sequenced and expressed. A degenerate primer was designed to the N-terminal amino acid sequence of the 16-kDa protein. The complete cDNA sequence was achieved by using reverse transcriptase PCR, PCR+1, standard cloning and sequencing techniques. The cDNA of Tyr p 2 is 552 nucleotides in length from the start codon including 126 nucleotides after the stop codon up to the beginning of the poly(A) tail. The leader sequence consists of 15 amino acids. Regarding the predicted amino acid sequence, there are no potential N-glycosylation sites (N-X-S/T). The sequence showed similarity to group II allergens from other mite species, and some regions are completely conserved. To show that the cloned cDNA sequence was coding for an allergen, Tyr p 2 was expressed in Escherichia coli and shown to react with a T. putrescentiae-positive serum pool.

Allergens↗

Contribution of disulphide bonds to antigenicity of Lep d 2, the major allergen of the dust mite Lepidoglyphus destructor.

To study the contribution of the 3 disulphide bonds in the major allergen Lep d 2 to the antigenic structure, site-directed mutagenesis was performed. Mutants with one or more cysteine residues altered were constructed with a histidine residue tag for purification purposes and expressed as recombinant proteins in E. coli. Seven mutants were analysed: 3 single mutants (Cys 8, Cys 21 and Cys 72), 3 double mutants (Cys 8-117, Cys 21-16 and Cys 72 77) and one mutant with all 6 cysteines altered (6 Cys). The evaluation of IgE reactivity in 10 allergic patients showed that the disulphide bond formed by cysteine 72 and 77 was the single most contributing bond to IgE binding. Mutants with disruption of the Cys 8-117 bond had a lesser reduction in IgE binding, even though this alteration seemed to influence the compact nature of Lep d 2. However, to abolish the IgE reactivity almost completely, all 6 cysteines had to be altered. A monoclonal antibody previously raised against Lepidoglyphus destructor showed a similar binding as human IgE with no reactivity to the Cys 72 77 or the 6 Cys mutant. Using skin prick test we found no reaction to the 6 Cys mutant at the concentrations tested (1-100 microg/ml) in an Lepidoglyphus destructor allergic patient, while the T-cell reactivity was preserved. The 6 Cys mutant of Lep d 2 may, after further evaluation, be a candidate molecule for improved immunotherapy of Lepidoglyphus destructor allergy.

Allergens↗