W R Thomas

University of Western Australia, Perth City, Western Australia, Australia

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Publications (167)687.28 Total impact

  • Susanne Vrtala, Hans Huber, Wayne R. Thomas
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    ABSTRACT: House dust mites (HDM) are a globally important source of allergen responsible for the sensitization of more than 50% of allergic patients. Specific immunotherapy with HDM extracts is effective but allergen extracts cannot be fully standardized and severe side-effects can occur during the protracted course of treatment. The introduction of molecular biological techniques into allergy research allowed the indentification of more than 20 groups of HDM allergens. Recombinant HDM allergens can be produced in defined concentrations and consistent quality and allow the development of vaccines for HDM allergy with reduced allergenic activity and retained immunogenicity. The immunotherapy trials in pollen allergic patients with recombinant pollen allergens/hypoallergenic allergen derivatives have shown that this treatment is effective and indicated that recombinant HDM vaccines might improve immunotherapy of HDM allergic patients. Here we report the steps for the development of vaccines for HDM allergy. After selection of the most prevalent HDM species, the panel of allergens to be included into a therapeutic vaccine for HDM allergy needs to be determined. HDM allergens with high IgE-binding frequency and clinical relevance will be modified into hypoallergenic variants and evaluated for their allergenic activity and immunogenicity. Derivatives with reduced allergenic activity but with retained immunogenicity would be good candidates for a HDM vaccine for safe and efficient immunotherapy.
    Methods 01/2014; 66(1):67–74. · 3.64 Impact Factor
  • Sarah B See, Wayne R Thomas
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    ABSTRACT: The ability of recombinant outer membrane proteins of Pasteurella pneumotropica to vaccinate against the infections of mice was studied. The proteins examined were the homologues of the P4, P6, P26, and D15 proteins of Haemophilus influenzae. Intranasal vaccination with P4 and P6 produced protection against pneumonia. P6 vaccination, which was most studied, reduced the peak bacteria load in lungs by 50-fold and caused a rapid resolution of an infection that lasted for at least 5 days in unvaccinated animals. Protection could be partially transferred with CD4(+) T cells and pulmonary challenge with the P6 antigen induced interferon-γ and the Th17 cytokine IL-21. This is the first demonstration of the ability of a recombinant P6 to mediate protective immunity to a pathogen in its natural host and it is proposed that it would not only have utility for mouse breeding but also for investigating how to improve the efficacy of vaccination with homologous proteins for related species.
    Microbes and Infection 04/2013; · 2.92 Impact Factor
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    ABSTRACT: The house dust mite (HDM) Dermatophagoides pteronyssinus is one of most important allergen sources and a major elicitor of allergic asthma. We screened a D. pteronyssinus expression cDNA library with IgE Abs from HDM allergic patients. A cDNA coding for a new major allergen was isolated, which showed sequence homology to peritrophins, which contain chitin-binding domains and are part of the peritrophic matrix lining the gut of arthropods. The mature Der p 23 allergen was expressed in Escherichia coli as an 8-kDa protein without its hydrophobic leader sequence and purified to homogeneity. It reacted with IgE Abs from 74% of D. pteronyssinus allergic patients (n = 347) at levels comparable to the two major HDM allergens, Der p 1 and Der p 2. Thus, Der p 23 represents a new major D. pteronyssinus allergen. Furthermore, rDer p 23 exhibited high allergenic activity as demonstrated by upregulation of CD203c expression on basophils from D. pteronyssinus allergic patients. Immunogold electron microscopy localized the allergen in the peritrophic matrix lining the midgut of D. pteronyssinus as well as on the surface of the fecal pellets. Thus, we identified a new major D. pteronyssinus allergen as peritrophin-like protein. The high allergenic activity of Der p 23 and its frequent recognition as respiratory allergen may be explained by the fact that it becomes airborne and respirable through its association with mite feces. Der p 23 may be an essential component for diagnosis and specific immunotherapy of HDM allergy.
    The Journal of Immunology 03/2013; · 5.52 Impact Factor
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    ABSTRACT: Background Cat allergy affects approximately 15% of the population and is a major risk factor for asthma. The relative importance of cat allergens other than Fel d 1 is not known. Objective To compare IgE and IgG antibody binding and T-cell recognition of the major cat allergen Fel d 1 with other cat proteins with known IgE binding properties. Methods IgE, IgG1, and IgG4 antibody to Fel d 1, 2, 3, 4, 7, 8, and the undesignated IgE binding proteins haptoglobin and S100A12 were measured in the plasma of 96 individuals with cat allergy and 78 individuals without cat allergy. Cytokines were measured from T cells stimulated with the cat allergens. Results An allergen other than Fel d 1 had the highest IgE binding specificity for 35% of individuals with cat allergy, and it bound more than 50% of their IgE antibody in 70% of these sera. Fel d 4, 7, and 8 were identified as the main contributors to the non–Fel d 1 IgE binding response and elicited inflammatory Th2 cytokines to a similar degree as Fel d 1. As expected, the average percentage of IgE binding to Fel d 1 for individuals was 55%. IgG4 binding to Fel d 1 was detected in both subjects with allergy (30%) and subjects without allergy (19%). IgG4 binding to the other allergens was less prevalent but was found for both groups. IgG1 antibody was not detected to any of the newly described cat proteins. Conclusion Fel d 4, 7, and 8 are allergens that should be included in the diagnosis and investigation of cat allergy.
    The Journal of Allergy and Clinical Immunology: In Practice. 01/2013; 1(6):656–665.e5.
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    ABSTRACT: Human rhinoviruses (HRV) are associated with upper and lower respiratory illnesses, including severe infections causing hospitalization in both children and adults. Although the clinical significance of HRV infections is now well established, no detailed investigation of the immune response against HRV has been performed. The purpose of this study was to assess the IgG1 antibody response to the three known HRV species, HRV-A, -B and -C in healthy subjects. Recombinant polypeptides of viral capsid protein 1 (VP1) from two genotypes of HRV-A, -B and -C were expressed as glutathione S-transferase (GST) fusion proteins and purified by affinity and then size exclusion chromatography. The presence of secondary structures similar to the natural antigens was verified by circular dichroism analysis. Total and species-specific IgG1 measurements were quantitated by immunoassays and immunoabsorption using sera from 63 healthy adults. Most adult sera reacted with the HRV VP1 antigens, at high titres. As expected, strong cross-reactivity between HRV genotypes of the same species was found. A high degree of cross-reactivity between different HRV species was also evident, particularly between HRV-A and HRV-C. Immunoabsorption studies revealed HRV-C specific titres were markedly and significantly lower than the HRV-A and HRV-B specific titres (P<0.0001). A truncated construct of HRV-C VP1 showed greater specificity in detecting anti-HRV-C antibodies. High titres of IgG1 antibody were bound by the VP1 capsid proteins of HRV-A, -B and -C, but for the majority of people, a large proportion of the antibody to HRV-C was cross-reactive, especially to HRV-A. The improved specificity found for the truncated HRV-C VP1 indicates species-specific and cross-reactive regions could be defined.
    PLoS ONE 01/2013; 8(8):e70552. · 3.73 Impact Factor
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    ABSTRACT: Background: The prevalence of IgE binding to the group 15 and 18 house dust mite (HDM) allergens of the Dermatophagoides species is reported to be >50% and they are the major allergens of HDM-sensitised dogs. The objective was to quantitate the IgE titres to Der p 15 and Der p 18 and evaluate their importance in human HDM sensitisation compared to the known major and mid-tier allergens. Methods: Der p 15 and Der p 18 were produced in Pichia pastoris, and their structure validated by circular dichroism. IgE binding was measured in 37 Australian HDM-allergic adults using a quantitative DELFIA™ assay. Results: The prevalence of IgE titres to Der p 15 and Der p 18 >0.1 ng/ml was low (38%) and only one subject had a titre >10 ng/ml to either allergen. The mean anti-Der p 15 and Der p 18 titres were 1.2 and 2.6 ng/ml, respectively, i.e. approximately 10- to 20-fold lower than the response to the major Der p 1 and Der p 2 allergens (p < 0.001). The IgE responses to Der p 15 and Der p 18 were lower than the mid-tier allergens Der p 5 and Der p 7 and although they correlated with each other, they did not correlate with titres to either the major or mid-tier allergens. Conclusions: Sensitisation to Der p 15 and Der p 18 makes a minor contribution to anti-HDM IgE titres, and the titres do not correlate with the size of the response to the major allergens.
    International Archives of Allergy and Immunology 10/2012; 160(3):233-240. · 2.25 Impact Factor
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    Wayne R Thomas
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    ABSTRACT: HDM allergy is associated with asthma, allergic rhinitis and atopic dermatitis. In many countries childhood asthma is predominantly found in HDM-allergic children with their probability of developing disease being proportional to their IgE antibody titers and the early development of Th2 responses. While the pathogenesis is complex and increasingly linked to infection the immunologically-based allergen immunotherapy and anti-IgE antibody therapy are highly beneficial. Immunotherapy could be a short-term treatment providing lifelong relief but the current regimens depend on repeated administration of allergen over years. Immunological investigations point to a contribution of responses outside the Th2 pathway and multiple potential but unproven control mechanisms. Over half of the IgE antibodies are directed to the group 1 and 2 allergens with most of remainder to the group 4, 5, 7 and 21 allergens. This hierarchy found in high and low responders provides a platform for introducing defined allergens into immunotherapy and defined reagents for investigation.
    Human vaccines & immunotherapeutics. 10/2012; 8(10).
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    ABSTRACT: BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are often linked to respiratory infections. However, it is unknown if COPD patients who experience frequent exacerbations have impaired humoral immunity. The aim of this study was to determine if antibodies specific for common respiratory pathogens are associated with AECOPD. METHODS: Plasma was obtained from COPD patients when clinically stable. AECOPD requiring hospitalisation were recorded. IgG1 antibodies to H. Influenzae outer membrane protein 6 (P6), pneumococcal surface protein C (PspC) and the VP1 viral capsid protein of rhinovirus were measured. RESULTS: COPD patients who had an AECOPD (n = 32) had significantly lower anti-VP1 IgG1 antibody levels when stable compared to COPD patients who did not have an AECOPD (n = 28, p = 0.024). Furthermore, the number of hospitalisations was inversely proportional to anti-VP1 antibody levels (r = 0.331, p = 0.011). In contrast, antibodies specific for P6 and PspC were present at similar concentrations between groups. Plasma IL-21, a cytokine important for B-cell development and antibody synthesis, was also lower in COPD patients who had an AECOPD, than in stable COPD patients (p = 0.046). CONCLUSION: Deficient humoral immunity specific for rhinoviruses is associated with AECOPD requiring hospitalisation, and may partly explain why some COPD patients have an increased exacerbation risk following respiratory viral infections.
    BMC Pulmonary Medicine 07/2012; 12(1):37. · 2.76 Impact Factor
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    ABSTRACT: More than 50% of allergic patients have house dust mite (HDM) allergy. Group 1 and 2 allergens are the major HDM allergens. We sought to produce and perform preclinical characterization of a recombinant hypoallergenic combination vaccine for specific immunotherapy of HDM allergy. Synthetic genes coding for 2 hybrid proteins consisting of reassembled Der p 1 and Der p 2 fragments with (recombinant Der p 2 [rDer p 2]/1C) and without (rDer p 2/1S) cysteines were expressed in Escherichia coli and purified to homogeneity by means of affinity chromatography. Protein fold was determined by using circular dichroism analysis, allergenic activity was determined by testing IgE reactivity and using basophil activation assays, and the presence of T-cell epitopes was determined based on lymphoproliferation in allergic patients. Mice and rabbits were immunized to study the molecules' ability to induce an allergic response and whether they induce allergen-specific IgG capable of inhibiting allergic patients' IgE binding to the allergens, respectively. rDer p 2/1C and rDer p 2/1S were expressed in large amounts in E coli as soluble and folded proteins. Because of the lack of disulfide bonds, rDer p 2/1S did not form aggregates and was obtained as a monomeric protein, whereas rDer p 2/1C did form aggregates. Both hypoallergens lacked relevant IgE reactivity and had reduced ability to induce allergic inflammation and allergic responses but induced similar T-cell proliferation as the wild-type allergens. Immunization with the hypoallergens (rDer p 2/1S > rDer p 2/1C) induced IgG antibodies in rabbits that inhibited the IgE reactivity of patients with HDM allergy to Der p 1 and Der p 2. The preclinical characterization indicates that particularly rDer p 2/1S can be used as a safe hypoallergenic molecule for both tolerance and vaccination approaches to treat HDM allergy.
    The Journal of allergy and clinical immunology 07/2012; 130(2):435-43.e4. · 12.05 Impact Factor
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    ABSTRACT: Background: Diagnosis and immunotherapy of house-dust mite (HDM) allergy is still based on natural allergen extracts. The aim of this study was to analyze commercially available Dermatophagoides pteronyssinus extracts from different manufacturers regarding allergen composition and content and whether variations may affect their allergenic activity. Methods: Antibodies specific for several D. pteronyssinus allergens (Der p 1, 2, 5, 7, 10 and 21) were used to analyze extracts from 10 different manufacturers by immunoblotting. Sandwich ELISAs were used to quantify Der p 1 and Der p 2 in the extracts. Mite-allergic patients (n = 45) were skin-tested with the extracts and tested for immunoglobulin E (IgE) reactivity to a panel of 10 mite allergens (Der p 1, 2, 4, 5, 7, 8, 10, 14, 20 and 21) by dot blot. Results: Only Der p 1 and Der p 2 were detected in all extracts but their concentrations and ratios showed high variability (Der p 1: 6.0-40.8 µg ml(-1); Der p 2: 1.7-45.0 µg ml(-1)). At least 1 out of 4 allergens (i.e. Der p 5, 7, 10 and 21) was not detected in 8 of the studied extracts. Mite-allergic subjects showed different IgE reactivity profiles to the individual mite allergens, the extracts showed different allergenic activity in skin-prick tests and false-negative results. Conclusions: Commercially available D. pteronyssinus extracts lack important allergens, show great variability regarding allergen composition and content and some gave false-negative diagnostic test results in certain patients.
    International Archives of Allergy and Immunology 06/2012; 159(3):253-62. · 2.25 Impact Factor
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    ABSTRACT: Innate properties that enhance immune responses might increase the propensity of certain allergens to induce allergic sensitization. Either a direct adjuvant effect or the increased immune response to the allergen could then increase allergic responses to bystander antigens. Here, we report on a model that does not use Th2-skewing adjuvants and yet achieves sensitization solely via the nasal mucosa. Animals were sensitized with either enzymatically active, inactive or non-activated cysteine proteases via the nasal mucosa. Following two sensitization phases, mice were challenged with a higher dose of allergen. For bystander sensitization, mice received recombinant Der p 2 at sensitization in conjunction with the cysteine protease and were challenged with rDer p 2 alone. Sensitization was determined by measuring allergen-specific antibody responses and cytokine and cellular infiltrates into the lungs following challenge. Sensitization for Th2-type lung hypersensitivity for both the cysteine protease and bystander antigens was readily achieved and both were dependent on the proteolytic activity of the allergen. Bystander adjuvant activity was demonstrated for mice that were low IgE responders to the cysteine protease, showing a response independent from the immune response to the enhancing cysteine protease. Airway hyperreactivity was induced in the susceptible NOD strain of mouse, and mice subjected to prolonged administration of papain maintained the ability to produce lung hypersensitivity and Th2-type responses. These experiments demonstrate that cysteine protease activity at low doses can be an adjuvant for respiratory Th2 responses for themselves and bystander antigens in the absence of another adjuvant.
    International Archives of Allergy and Immunology 04/2012; 158(4):347-58. · 2.25 Impact Factor
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    ABSTRACT: BACKGROUND: Vaccines including conserved antigens from Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) have the potential to reduce the burden of acute otitis media. Little is known about the antibody response to such antigens in young children with recurrent acute otitis media, however, it has been suggested antibody production may be impaired in these children. METHODS: We measured serum IgG levels against 4 pneumococcal (PspA1, PspA 2, CbpA and Ply) and 3 NTHi (P4, P6 and PD) proteins in a cross-sectional study of 172 children under 3 years of age with a history of recurrent acute otitis media (median 7 episodes, requiring ventilation tube insertion) and 63 healthy age-matched controls, using a newly developed multiplex bead assay. RESULTS: Children with a history of recurrent acute otitis media had significantly higher geometric mean serum IgG levels against NTHi proteins P4, P6 and PD compared with healthy controls, whereas there was no difference in antibody levels against pneumococcal protein antigens. In both children with and without a history of acute otitis media, antibody levels increased with age and were significantly higher in children colonised with S. pneumoniae or NTHi compared with children that were not colonised. CONCLUSIONS: Proteins from S. pneumoniae and NTHi induce serum IgG in children with a history of acute otitis media. The mechanisms in which proteins induce immunity and potential protection requires further investigation but the dogma of impaired antibody responses in children with recurrent acute otitis media should be reconsidered.
    PLoS ONE 01/2012; 7(11):e49061. · 3.73 Impact Factor
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    ABSTRACT: Infants who develop house dust mite (HDM) allergy and HDM-sensitised children with severe persistent asthma have low antibody responses to the P6 antigen of Haemophilus influenzae. To measure the development of antibody to two ubiquitous bacteria of the respiratory mucosa in a prospective birth cohort at high risk of allergic disease and to assess which responses are associated with asthma and atopy. IgG1 and IgG4 antibody to H influenzae (P4 and P6) and Streptoccocus pneumoniae (PspA and PspC) surface antigens was measured in yearly blood samples of children aged 1-5 years. IgE to the P6 antigen was examined for the 5-year group. The children were stratified based on HDM sensitisation and asthma at 5 years of age. HDM-sensitised children had lower IgG1 antibody titres to the bacterial antigens, and early responses (<3 years and before the development of HDM sensitisation and asthma) corrected for multiple antigens were significantly reduced for P4, P6 and PspC (p=0.008, p=0.004 and p=0.028, respectively). Similar associations with asthma were also found (p=0.008, p=0.004 and p=0.032 for P4, P6 and PspC, respectively). The IgG4 antibody titre and prevalence were similar in both HDM-sensitised and non-sensitised groups, but sensitised children had a slower downregulation of the IgG4 response. Children with asthma (27/145 at 5 years) had lower anti-P6 IgE responses (p<0.05). HDM-sensitised children have early defective antibody responses to bacteria that are associated with asthma. Surprisingly, antibacterial IgE was associated with a reduced risk for asthma.
    Thorax 11/2011; 67(4):321-7. · 8.38 Impact Factor
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    ABSTRACT: Tropomyosins represent clinically relevant seafood allergens but the role of mite tropomyosin, Der p 10, in house dust mite (HDM) allergy has not been studied in detail. To express and purify a recombinant Der p 10 with equivalent IgE reactivity as natural Der p 10 and to evaluate its IgE reactivity and allergenic activity in HDM-allergic patients. rDer p 10 was expressed in Escherichia coli, purified and characterized by mass spectrometry and circular dichroism. It was tested for IgE reactivity in 1322 HDM-allergic patients. Detailed IgE-reactivity profiles to six HDM allergens (Der p 1, 2, 5, 7, 10, 21) were established for subgroups of Der p 10-positive and -negative patients. The allergenic activity of rDer p 10 was evaluated in basophil degranulation experiments. rDer p 10 is an α-helical protein sharing IgE epitopes with nDer p 10. It is recognized by 15.2% of HDM-allergic patients. Der p 10-negative patients were primarily sensitized to Der p 1 and/or Der p 2, whereas Der p 10-positive patients reacted to several other HDM allergens besides the major allergens (Der p 1, Der p 2) or showed a rather selective Der p 10 reactivity. The allergenic activity of Der p 10 was generally low but patients could be identified who suffered from clinically relevant HDM allergy due to Der p 10 sensitization. Der p 10 may be a diagnostic marker for HDM-allergic patients with additional sensitization to allergens other than Der p 1 and Der p 2. Such patients may require attention when allergen-specific immunotherapy is considered.
    Clinical & Experimental Allergy 06/2011; 41(10):1468-77. · 4.79 Impact Factor
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    ABSTRACT: Characterization of the complete IgE binding spectrum of cat allergens is important for the development of improved diagnosis and effective immunotherapeutics. While Fel d 1 remains unchallenged as the major cat allergen, we now report the isolation of two new allergens capable of binding similar concentrations of IgE in the allergic sera of some individuals. Cat tongue and submandibular salivary gland cDNA libraries were screened by DNA hybridisation and IgE immunoassay. The isolated DNA fragments were sub-cloned into an E. coli expression system and the IgE reactivity was examined with human cat-allergic sera using a DELFIA IgE quantitation assay. Fel d 7, an 18 kDa von Ebner gland protein Can f 1 homologue, was isolated from the tongue library. Fel d 8, a 24-kDa latherin-like protein with homology to Equ c 5, was isolated from the submandibular library. The frequency of IgE binding of cat-allergic sera to recombinant Fel d 1, 7 and 8 was 60.5, 37.6 and 19.3%, respectively. Inhibition studies indicated some IgE binding cross-reactivity between Fel d 7 and dog dander extracts. The study reports the isolation and characterization of two new cat allergens. The isolation of these allergens provides the opportunity to determine the role that IgE binding proteins other than Fel d 1 play in cat-allergic disease. For cat-allergic individuals with moderate to mild rhinoconjunctivitis these allergens may play a more important role in the manifestation of their allergic disease.
    International Archives of Allergy and Immunology 05/2011; 156(2):159-70. · 2.25 Impact Factor
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    William A Sewell, Wayne R Thomas
    Immunology and Cell Biology 03/2011; 89(7):749-50. · 3.93 Impact Factor
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    ABSTRACT: The group 7 allergens are important allergenic specificities for mite-sensitive patients and may need to be incorporated into new diagnostic and therapeutic strategies. However, little is known about their biological and structural features. Position-specific iterative BLAST showed that they had strong ancestral homology to two related families of lipid-binding proteins, namely, the bactericidal permeability-increasing (BPI) proteins and the odorant-binding protein. A three-dimensional model of Der f 7 made with the Phyre and SWISS-MODEL homology-modeling servers showed a close match with the human BPI coordinates used for its construction. The binding of the monoclonal antibody HD12 known to block IgE binding could be blocked by the linear sequence (46GILDF50) with a critical role for L48 or F50. These hydrophobic residues were located on a surface loop of the model. The properties of Der f 7 that can be deduced from the model provide avenues for further characterizing these allergens, their IgE binding structures and biological properties that can enhance allergenicity.
    Immunology and Cell Biology 02/2011; 89(2):225-30. · 3.93 Impact Factor
  • Wayne R Thomas
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    ABSTRACT: When the allergen nomenclature system was adopted in 1986, allergens were identified by their behavior on electrophoresis and chromatography and by reactivity to shared antisera. Not only was this unsatisfactory for standardization, but the processes of allergic sensitization and immunotherapy could not be studied in the framework of antigen processing and B- and T-cell epitopes. Recombinant technologies developed in the 1980s for cloning cDNA from low-abundance mRNA permitted the cloning of allergens, beginning with the major house dust mite allergen Der p 1 and hornet allergen Dol m 5. After this, a wave of cloning with IgE immunoscreening resulted in the cloning of Der p 2, Der p 5, Bet v 1, Bet v 2, and Dac g 2 along with Fel d 1 cloned after amino acid sequencing. Recombinant allergens have now been used to define the important allergens for a wide range of allergies and to develop new types of immunotherapy, some of which have shown efficacy in human trials. The clonally pure allergens have been used to solve the tertiary structures of allergens and from this how allergens might activate innate immunity. Proprietary recombinant allergens are now being used in improved diagnostic tests.
    The Journal of allergy and clinical immunology 01/2011; 127(4):855-9. · 12.05 Impact Factor
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    Wayne R Thomas
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    ABSTRACT: To consider how the different distribution of house dust mites and their species in different geographical locations affects the allergens in the environment and their use. Data were obtained from Medline, Genbank and library and web searches. A comprehensive description of the genetic variations of allergens is given. The distribution of house dust mites is illustrated with publications that either make pertinent observations or would be useful for a broad appreciation of their geographical distribution. The review identifies regions where glycyphagid house dust mites have been found and the distribution of the pyroglyphid Dermatophagoides spp. The antigenic differences the allergens of D. pteronyssinus and D. farinae are outlined and how this should affect optimal allergen usage in different regions. The allelic variations within the major allergens of Dermatophagoides sp. are similarly presented. While there is a broad knowledge of the distribution of different species of house dust mites, regions that require further examination have been identified and there are examples of incorrect use of allergens for different regions. The extension of allergy research and practice into new regions will benefit from allergen formulations designed for regional use. Specific knowledge of the allergens in the environments will be required to optimally implement some of the new molecularly-defined medicaments currently being developed for effective allergy vaccination and immunotherapy.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 12/2010; 28(4):211-24. · 0.79 Impact Factor
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    ABSTRACT: Bacterial colonisation of the airways is associated with increased risk of childhood asthma. Immunoglobulin (Ig)E against bacterial antigens has been reported in some asthmatics, suggesting a role for bacterial-specific type-2 immunity in disease pathogenesis. We aimed to investigate relationships between bacterial-specific IgE amongst teenagers and asthma susceptibility. We measured titres of IgE against Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus in 1,380 teenagers, and related these to asthma symptomatology and immunophenotypes. IgE titres against S. aureus-derived enterotoxins were highest amongst atopics and were associated with asthma risk. Surprisingly, IgE titres against H. influenzae and S. pneumoniae surface antigens were higher, not stratified by atopy and independently associated with decreased asthma risk. The positive association between type-2 immunity to S. aureus and asthma phenotypes probably reflects IgE-mediated effector cell activation via enterotoxin super antigens which are secreted in soluble form. The contrasting benign nature of type-2 immunity to H. influenzae and S. pneumoniae antigens may reflect their lower availability in soluble forms that can crosslink IgE receptors. We theorise that instead they may be processed by antigen presenting cells and presented to type-2 memory cells leading to mucosal secretion of interleukin (IL)-4/IL-13, a mechanism widely recognised in other tissues to attenuate T-helper-1 associated bacterial-induced inflammation.
    European Respiratory Journal 09/2010; 36(3):509-16. · 6.36 Impact Factor

Publication Stats

5k Citations
870 Downloads
687.28 Total Impact Points

Institutions

  • 1993–2014
    • University of Western Australia
      • • Centre for Health Services Research
      • • Molecular Biotechnology Team
      • • Telethon Institute for Child Health Research (ICHR)
      Perth City, Western Australia, Australia
    • University of Cambridge
      Cambridge, England, United Kingdom
    • Flinders University
      • Department of Paediatrics and Child Health
      Adelaide, South Australia, Australia
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 1997–2013
    • Medical University of Vienna
      • • Institut für Pathophysiologie und Allergieforschung
      • • Zentrum für Pathophysiologie, Infektiologie und Immunologie
      Vienna, Vienna, Austria
    • National Yang Ming University
      T’ai-pei, Taipei, Taiwan
  • 2011
    • Garvan Institute of Medical Research
      Darlinghurst, New South Wales, Australia
  • 1995–2011
    • Taipei Veterans General Hospital
      • Department of Medical Research and Education
      Taipei, Taipei, Taiwan
  • 2006
    • Phylogica
      Perth City, Western Australia, Australia
    • Mahidol University
      • Institute of Molecular Biosciences
      Bangkok, Bangkok, Thailand
    • University of Oxford
      Oxford, England, United Kingdom
  • 2004
    • Moredun Research Institute
      • Department of Parasitology
      Penicuik, Scotland, United Kingdom
  • 2001
    • University of Virginia
      • Asthma and Allergic Diseases Center
      Charlottesville, VA, United States
  • 1999–2000
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
  • 1994–1999
    • University of Melbourne
      • Department of Medicine
      Melbourne, Victoria, Australia
  • 1997–1998
    • Central University of Venezuela
      • Instituto de Biomedicina
      Caracas, Distrito Capital, Venezuela
  • 1994–1996
    • Imperial College London
      • • Section of Infectious Diseases and Immunity
      • • Section of Immunology
      London, ENG, United Kingdom
  • 1992–1996
    • Western Australia Health
      Perth City, Western Australia, Australia
  • 1988–1993
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada