Detection of Environmental Influences and Allergens Bergmann K-C, Ring J (eds): History of Allergy. Chem Immunol Allergy. Basel, Karger, 2014, vol 100, pp 234–242 DOI: 10.1159/000358860
Mites and Allergy Enrique Fernández-Caldas a, b · Leonardo Puerta c · Luis Caraballo c a Inmunotek SL, Madrid, Spain; b Division of Allergy and Immunology, College of Medicine, University of South Florida, Tampa, Fla., USA; c Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
Allergic diseases triggered by mite allergens include allergic rhinoconjunctivitis, asthma, atopic dermatitis and other skin diseases. Since the early discovery of the allergenic role of mites of the genus Dermatophagoides in the mid 1960s, numerous species have been described as the source of allergens capable of sensitizing and inducing allergic symptoms in sensitized and genetically predisposed individuals. The main sources of allergens in house dust worldwide are the fecal pellets of the mite species D. pteronyssinus, D. farinae, Euroglyphus maynei and the storage mites Blomia tropicalis, Lepidoglyphus destructor and Tyropahgus putrescentiae. Group 1 and 2 allergens are major house dust mite allergens. The main allergens in storage mites include fatty acid-binding proteins, tropomyosin and paramyosin homologues, apolipophorin-like proteins, α-tubulins and others, such as group 2, 5 and 7 allergens. Cross-reactivity is an important and common immunological feature among mites. Currently, purified native or recombinant allergens, epitope mapping, proteomic approaches and T cell proliferation techniques are be-
ing used to assess cross-reactivity. Mites contain potent enzymes capable of degrading a wide range of substrates. Most mite allergens are enzymes. Advances in genomics and molecular biology will improve our ability to understand the genetics of specific IgE responses to mites. Mite allergen avoidance and immunotherapy are the only two allergen-specific ways to treat miteinduced respiratory and cutaneous diseases. © 2014 S. Karger AG, Basel
In 1922, Giocomo R. Ancona (1886–1976) studied 21 mill workers suffering from asthma and realized that the disease was induced by the grain mite, Pediculoides ventricosus [1]. It was novel to establish mites as a possible trigger of asthma and identified a potentially important new source of allergens. Later on, the scientist and physician Willem Storm van Leeuwen (1882–1933; fig. 1) became interested in ‘house-dust asthma’, inspired by publications in the USA. Cooke [2] suggested in 1922 that a specific allergen could be responsible for the allergenicity of house dust. One of the main problems associated Downloaded by: UCONN Storrs 198.143.38.1 - 7/6/2015 8:07:26 PM
Abstract
Fig. 2. Reindert Voorhorst.
with house dust was that skin tests with other allergen extracts often remained negative, but provocations with the dust induced asthma attacks. Storm van Leeuwen indicated that ‘intradermal skin reactions may serve to diagnose the allergic state, but not to make a specific diagnosis. … Doubtless cases of allergy exist which give negative skin tests … with an extract of the allergen which causes the attacks’ [3]. In 1923, Storm van Leeuwen conducted a very special experiment. He went with three asthmatic individuals from the Netherlands to the high mountain area near St. Moritz in Switzerland. Within a few
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Fig. 1. Willem Storm van Leeuwen.
days the asthmatic patients were free of asthma symptoms. However, when the patients inhaled house dust contained in a box and sampled from their flats, they also had exacerbations of their asthma in St. Moritz [4]. It had already been known for many years that asthmatic patients had fewer symptoms in high mountain areas, but now an explanation for the reason had been provided. In 1931, Peipers [5] suggested the presence of numerous allergens in house dust. However, it was not until 1964 that the Dutch group comprised of R. Voorhorst (fig. 2) and the married couple F.T. Spieksma and M.I. Spieksma-Boezeman (fig. 3) demonstrated the presence of house dust mites in dust samples collected in flats in Juliana Street in Leiden, the Netherlands (fig. 4). Mrs. Spieksma-Boezeman was able to demonstrate that mites are the main allergen source in house dust [6]. She also established that there were clearly more mites in the dust from a damp house and that the allergen content was also higher. One of the first appreciations of the new idea of mites as the origin of the house dust allergen came from Jack Pepys [7], as well as from other groups that published confirmative reports [8]. Simultaneously, the Japanese biologist Shiro Oshima, trying to identify parasites causing skin afflictions in schoolchildren in Yokohama, reported the finding of Dermatophagoides species in ‘tatami’ floor coverings [9]. Contact with Japanese colleagues resulted in the first confirming report from countries outside of Europe [10]. Many other scientists and physicians collaborated in the discovery and establishment of house dust mites as one of the most important sources of allergens in house dust worldwide, and we extend our most sincere recognition to them all. Since the early demonstration that dust mites were the origin of the allergenicity of house dust, numerous mite species have been described as the source of allergens capable of sensitizing and inducing allergic symptoms in sensitized and genetically predisposed individuals [11]. The overall treatment of these miteallergic patients focuses primarily on education, the reduction of allergen exposure, pharmacotherapy to reduce allergic inflammation and bronchoconstriction, and immunotherapy. Patients who are exposed to large quantities of mite allergens may experience a
Fig. 3. Family Spieksma: Frits T.M. Spieksma and Marise Spieksma-Boezeman.
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Fig. 4. Bottle with a dust sample collected in 1964 in which mites were detected by Spieksma-Boezeman and Spieksma. The content of the little bottle is a small portion from a mixture of two 5-gram samples of floor dust collected with a vacuum cleaner from the ground floor of a small house in Leiden on October 13, 1964. It was part of a sampling series from three houses with different grades of dampness. The address was Julianastraat 48 and it was the dampest of the three. Samples were taken every 3 weeks. The house does not exist anymore – it was demolished because of poor quality. From the two original 5-gram samples, mites were isolated and counted as described in two published articles [50, 51] and in a personal communication from Frits Spieksma to K.C. Bergmann. Approximately 1,600 mites of the genus Dermatophagoides, almost exclusively D. pteronyssinus, were identified in the sample.
progressive deterioration in PD20FEV1. This fact is consistent with a chronic inflammatory and remodeling process of the lungs, as has been suggested for several animal models, including rhesus monkeys, sheep and mice [12]. There is ample evidence that continuous exposure to mites is an important risk factor for the development of sensitization, allergic respiratory diseases and chronic inflammation of the lungs. Sensitization to house dust mites is a major independent risk factor for asthma in all areas where the climate is conducive to mite population growth. It has been demonstrated that there is a significant dose-response relationship between exposure to mite allergens and subsequent sensitization. Exposure to house dust mite antigen can induce airway epithelial shedding even in subjects with low eosinophil airway infiltration, thus supporting the idea that epithelial damage in asthmatics sensitized to Dermatophagoides may be due to the proteolytic activity of the mite allergens [13]. The most studied species belong to the family Pyroglyphidae, especially D. pteronyssinus, D. farinae and Euroglyphus maynei, and are called house dust mites. House dust mites are commonly present in human dwellings and are especially abundant in mattresses, sofas, carpets and blankets. Numerous mite allergens have been purified, sequenced and cloned. An important group of mites, referred to as
Allergens from House Dust Mites Mite allergens are present in mite bodies, secretion and excretion. Fecal particles contain the greatest proportion of mite allergen [18]. Mite allergens can be detected in many areas of the home, including beds, carpets, upholstered furniture and clothing. Leather-covered couches, wooden furniture and bare floors contain fewer. Beds are the perfect habitat for mites since they provide the ideal temperature, food and moisture for their proliferation, and the allergens they produce accumulate deep inside mattresses and pillows, especially when they are old. Information on the distribution of house dust mites provides valuable information with which to design environmental control strategies. They can also be detected in the air; studies using volumetric samples equipped with sizing devices have shown that mite allergens remain airborne for a short period of time. Allergenic activity has been detected in particles
Mites and Allergy
smaller than 1 μm and in particles larger than 10 μm. It has been suggested that mite fecal pellets may occasionally enter the lung and cause inflammation and bronchoconstriction [19]. Most of the isolated allergens have been placed in groups based on their chronological characterization and/or homology with previously purified allergens. Purified allergens are named according to the first three letters of the genus, the first letter of the species and a number indicating the group in which they are placed. Thus, the first identified allergen of D. pteronyssinus was named Der p 1 and belongs to group 1. When several isoforms exist they have to be reflected in the denomination, e.g. Der p 1.0101 and Der p 1.0201. The best-studied groups are group 1 (Der p 1 and Der f 1) and group 2 (Der p 2 and Der f 2). They are considered major allergens based on the frequency of patients sensitized and the amount of specific IgE. In Europe, more than 95% of mite-allergic patients are sensitized to Der p 1 and Der p 2. Der p 1 is a glycoprotein with sequence homology and thiol protease functions similar to the enzymes papain, actinidin, bromelain and cathepsins B and H [20]. Der p 1 may upregulate the IgE synthesis by cleaving the low-affinity IgE receptor (CD23) from the surface of human B cell lymphocytes [21]. Der p 1 may also cleave the α-subunit of the interleukin (IL)-2 receptor (IL2R or CD25) from the surface of human peripheral blood T cells and, as a result, these cells show markedly diminished proliferation and interferon-γ secretion, which consequently bias the immune response towards Th2 cells. It has been shown that the cysteine protease activity of Der p 1 seems to selectively enhance the IgE response and that the proteolytic activity of Der p 1 conditions T cells to produce more IL-4 and less interferon-γ [22, 23]. The enzymatic activity for Der p 1 and other mite allergens may also contribute to their immunogenicity by increasing mucosal permeability. Der p 1 and Der f 1 also cleave SP-A and SP-D lung collectins which have protective roles in allergy. The cleavage and consequent inactivation of SP-A and SP-D may be a novel mechanism to account for the potent allergenicity of Der p 1 and Der f 1 [24]. Due to its high prevalence in house dust and worldwide distribution, the group 1 allergen is used as a standard to
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‘storage mites’, mainly comprises members of the Acaridae and Glycyphagidae families that live in stored food and grains. All mite species present in the home environment and capable of inducing immunoglobulin (Ig) E-mediated sensitization are called ‘domestic mites’ [14]. Approximately 150 storage mite species are known [15], and approximately 20 can be considered to be important from an economic and sanitary perspective [16]. The most studied species are Blomia tropicalis, due to its abundance in tropical and subtropical regions of the world [17], and Lepidoglyphus destructor, because of its frequent presence in barns. Storage mite species can be present in kitchen floor dust, cupboards and pantries. In humid homes, storage mites can also be found in mattress dust. They can be an important plague with economical consequences and cause occupational respiratory allergies in farmers and other occupationally exposed individuals. The most important genera are Lepidoglyphus (family Glycyphagidae), Glycyphagus (family Glycyphagidae), Acarus (family Acaridae), Tyrophagus (family Acaridae), Aleuroglyphus (family Acaridae), Suidasia (family Suidasidae), Chortoglyphus (family Chortoglyphidae) and Cheyletus (family Cheyletidae).
Table 1. Biological function, molecular weight (MW) and prevalence of specific IgE binding of several mite allergens [adapted from 50]
Group Biological function
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
MW, kDa
Cysteine protease 25 Niemann-pick type C2 protein 14 Recognition and binding of lipids; similar to MD-2 Trypsin 28 – 30 α-Amylase 57 Unknown 15 Chymotrypsin 25 Lipid-binding protein; similar to pro- 22 – 31 teins in the TLR pathway Glutathione-S-transferase 26 Collagenolytic serine protease 30 Tropomyosin 33 – 37 Paramyosin 92 – 110 Unknown 14 Fatty acid-binding proteins 14 – 15 Lipid-binding apolipophorin 177 Chitinase 98 – 109 Gelsolin-like protein/villin 53 EF-hand calcium-binding protein 53 60-kDa chitinase 60 Antimicrobial peptide 7.2 Arginine kinase 40 Unknown 13.2 Unknown 14 Homology to peritrophin-A domain 14 Troponin C 18
Mite species
IgE binding, %
Dp, Df, Dm, Ds, Em, Bt, As, Ao, Sm, Tp Dp, Df, Dm, Ds, Em, Ld, Gd, Bt, As, Ao, Sm, Tp
70 – 100 80 – 100
Dp, Df, Dm, Ds, Em, Gd, Bt, As, Ao, Sm, Tp Dp, Df, Em, Bt, As, Sm, Tp Dp, Df, Ds, Ld, Gd, Bt, Ao, Sm, Tp Dp, Df, Ds, Bt, Ao, Sm Dp, Df, Ld, Gd, Bt, As, Ao, Sm, Tp
16 – 100 25 – 46 50 – 70 40 50
Dp, Df, Ld, Gd, Bt, As, Ao, Sm Dp, Df, Dm, Bt, Ao, Sm Dp, Df, Ld, Gd, Bt, As, Ao, Sm, Tp, Ca Dp, Df, Dm, Bt Bt Dp, Df, Ld, Gd, Bt, As, Ao, Sm, Tp Dp, Df, Dm, Em, Bt Dp, Df, Dm, Bt Df Df Dp, Df Bt Dp, Df, Ao Dp, Bt Dp, Df, Ao, As, Tp Dp Tp
40 90 50 – 95 80 50 10 – 23 90 70 35 35 50 – 60 10 ? ? ? 74 10.6
Ao = A. ovatus; As = A. siro; Bt = B. tropicalis; Ca = C. arcuatus; Df = D. farinae; Dm = D. microceras; Dp = D. pteronyssinus; Em = E. mayne; Gd = G. domesticus; Ld = L. destructor; Tp = T. putrescentiae; Sm = S. medanensis.
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might be enhanced by a similar interaction. It has been demonstrated that rDer p 2 could act directly on airway smooth muscle cells activating the TLR2 signaling pathway, but not on TLR4. A list containing the most relevant and characterized mite allergens is shown in table 1.
Allergens from Storage Mites Several storage mite allergens have been purified, cloned and sequenced [30]. Some of these allergens can be considered as pan allergens and are present in B. tropicalis, L. destructor, G. domesticus, T. putres-
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estimate environmental exposure to Dermatophagoides spp. in the indoor environment. Der p 2 and Der f 2 are heat- and pH-stable proteins of 14 kDa [25, 26]. These allergens have 88% sequence similarity. In their native stage and expressed as a fusion protein, both have an 83% frequency of specific IgE recognition [27]. Crystallographic studies suggest that Der p 2 is a lipid-binding protein [28]. Der f 2 binds lipopolysaccharide (LPS) in a manner similar to the binding by MD-2. The hydrophobic LPS-binding residues are similar in all of the group 2 allergen sequences [29]. Considering that MD-2 loads LPS onto Toll-like receptor (TLR) 4, it has been suggested that group 2 allergenicity
Family
Species
Glycyphagidae
Glycyphagus domesticus Glycyphagus privatus Gohieria fusca Lepidoglyphus destructor Blomia tropicalis Blomia kulagini Blomia tjibodas Chortoglyphus arcuatus Suidasia medanensis Tyrophagus putrescentiae Tyrophagus longior Acarus siro Acarus farris Thyreophagus entomophagus Aleuroglyphus ovatus Cheyletus eruditus Cheyletus tenuipilis Cheyletus malaccensis
Echimyopodidae Chortoglyphidae Ebertiidae Acaridae
Cheyletidae
centiae, A. siro, A. ovatus, S. medanensis and Thyreophagus entomophagus. Table 2 shows a list of the main families and species of storage mites that have been described as allergenic [31]. Some of these allergens have shown sequence homology and biological function similar to those previously described in Dermatophagoides spp. (see table 1). The main allergens described in storage mites include fatty acidbinding proteins, tropomyosin and paramyosin homologues, apolipophorin-like proteins, α-tubulins and others, such as group 2, 5 and 7 allergens. A list of other mite families and species of allergenic mites, excluding house dust and storage mites, is shown in table 3.
Cross-Reactivity of Mite Allergens Cross-reactivity is a common feature among mite allergens, especially in those from taxonomically related species. Cross-reactivity may also be the cause of mite polysensitization, which is observed in some mite-allergic individuals. Cross-reactivity among group 2 allergens from storage mites, L. destructor, T. putrescentiae and G. domesticus is high, whereas
Mites and Allergy
Table 3. Other mite families and species of allergenic mites, excluding house dust and storage mites
Family Parasites of plants Predator
Parasites of animals
Species
Tetranychidae
Tetranychus urticae Panonychus ulmi Panonychus citri Tydeidae Pronematus davisi Phytoseiidae Amblyseius cucumeris Phytoseiulus persimilis Hypoaspidae Hypoaspis miles Hemisarcoptidae Hemisarcoptes cooremani Varroaidae Varroa spp. Sarcoptidae Sarcoptes scabiei Analgidae Diplaegidia columbae Ixodidae Ixodes pacificus Ixodes holociclus Ixodes ricinus Riphicephalus spp. Argas reflexus Argasidae
there is only limited cross-inhibition between Der p 2 and the non-pyroglyphid mite allergens. This lack of cross-reactivity between Der p 2 and the group 2 of storage mites is a result of the multiple amino acid substitutions across the surface [32]. Other studies have shown limited cross-reactivity between D. pteronyssinus, L. destructor and T. putrescentiae [33, 34], but others have reported a greater cross-reactivity between Dermatophagoides and T. putresentiae [35]. A low degree of cross-reactivity between D. pteronyssinus, A. siro and T. putrescentiae was described in one study, whereas cross-reactivity between L. destructor and A. siro was high [36]. Individuals allergic to the Dermatophagoides spp. may experience allergic symptoms after eating crustaceans and mollusks. Der f 10 and Der p 10, proteins with homology to tropomyosin from various animals, are involved in the cross-reactivity among Dermatophagoides spp., mollusks and crustaceans. The 36-kDa crossreactive tropomyosin present in mites, various insects (chironomids, mosquitoes and cockroaches) and shrimp [37] is responsible for cross-reactivity among different arthropods [38]. Immunochemical studies have demonstrated that allergens from snails, crustaceans, cockroaches and chironomids cross-re-
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Table 2. Main families and species of storage mites that have been described as allergenic
Effect of Parasitic Infections on Mite Allergy The association of allergy with helminthiases was perceived before the discovery of IgE. However, being able to detect blood levels of this antibody allowed the discovery of the first shared phenotype between ascariasis and asthma: high total IgE levels. This raised the idea that the allergic and anti-parasitic immune responses were similar and, in addition, helminth infections could increase the symptoms of allergy. However, later studies have shown a low prevalence of both allergy and positivity of skin tests (including mites) in areas of great endemicity of helminth infections, suggesting that chronic and high-parasite-load infections induce immunosuppression, an aspect that has been widely documented in recent years although the mechanisms are not fully elucidated [41, 42]. Similarly, in regions with low endemicity where helminth infections are mild-tomoderate and deworming programs are permanent, it has been shown that allergic diseases such as asthma are more common. This is an important historical point since it involves the manifestations of allergy in almost half of the world’s population, among which hygiene conditions are improving progressively, the severity of parasitic infections is diminishing and the prevalence of allergies is increasing, es-
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pecially in urban settings [43]. An important advancement has been made with the description of cross-reactivity between mites and Ascaris allergens [39]. Several scenarios should be considered to explain the immunological interaction between mites and parasites. First, there are many chances of early life exposure to allergens from mites and antigens and A. lumbricoides. This has been observed in children from tropical regions [44, 45]. Second, parasitized preschool and school-aged children in underdeveloped tropical countries receive regular antihelminth drug therapy during mass deworming programs. Since the fundamental socio-economic causes of the infections are not eliminated, children become re-infected several times and this sort of modified secondary immune response may be boosters of the IgE reactivity against cross-reactive allergens from other sources (e.g. mites). Third, mite allergen exposure is perennial and very intense in the tropics; therefore, in the Ascaris-infected population (current or past) susceptible to asthma, this may be another cause of the increasing IgE responses to cross-reactive allergens. To better study the effects of the immune responses to Ascaris on allergy, it is important to identify the molecules that induce allergy symptoms, those that generate a protective IgE immune response and those that promote both effects. A systematic approach to identify the antigens and allergens of A. lumbricoides, inducing immune responses in humans, is needed.
Environmental Control The methods recommended for reducing exposure to house dust mite allergens have not changed much over the last 30 years. The implementation of these methods has provided inconsistent clinical benefit [46], especially in longitudinal prevention studies. However, studies using very strict measures have produced positive results. Evidence that mite allergy is more common in certain countries suggests that there are critical environmental factors which influence the prevalence, incidence and severity of mite-allergic asthma. The main question remains of whether we are able to control or influence these conditions. It is well established that ambient
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act with house dust mite allergens. However, house dust mites are usually the primary source of sensitizing allergens. Tropomyosin is also involved in the cross-reactivity between mites and parasites. A high degree of cross-reactivity between extracts of house dust mites and Ascaris has been demonstrated. Several allergens are implicated, such as tropomyosin and glutathione-S-tranferases [39]. A. lumbricoides tropomyosin (Asc l 3) is an allergen cross-reactive with mite tropomyosins. IgE reactivity to this allergen is very frequent in both asthmatic and normal subjects sensitized to Ascaris [40]. Filarial and mite tropomyosins are similar, with a 72% identity at the amino acid level and overlapping predicted 3D structures. Filarial infection induces strong cross-reactive antitropomyosin antibody responses that may affect sensitization and regulation of allergic reactivity.
humidity and temperature are important factors for the development of mite allergy. Other factors, such as exposure to irritants, adjuvants or substances interacting directly with the innate immune system, remain less clear. The role of allergen exposure in the etiology of allergic sensitization and asthma is very complex [47]. Allergen avoidance is a successful treatment for occupational asthma in many settings and, as such, it should be considered for other occupational or environmental diseases. Although many strategies may reduce allergen levels, its effect in reducing inflammation is not so obvious. Removal of carpets, changing old mite-infested mattresses, pillows and sofas, and improving ventilation are all changes that make sense, but in some cases are not enough to produce a clinical benefit. It is also evident that a successful strategy would be attacking the mite reservoirs with a combination of methods – just one action alone is not enough. Controlling exposure to mite aeroallergens and adjuvant factors seems mandatory.
Mite Immunotherapy Sensitivity and exposure to high levels of mite allergens is an important risk factor for developing and maintaining bronchial hyperreactivity [48]. However, in light of publications that have shown pessimistic results using environmental control measures, immunotherapy with mite extracts has emerged as a solid treatment of mite-induced allergic respiratory diseases. Numerous studies have shown the efficacy of mite sublingual and subcutaneous immunotherapy [12]. The future treatment of mite-induced allergies will not be changed much, although it will be based on a more accurate diagnosis and better immunotherapy treatments. The need to improve the quality of current allergen extracts for diagnosis and treatment is clear [49].
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23 Ghaemmaghami AM, Robins A, Gough L, Sewell HF, Shakib F: Human T cell subset commitment determined by the intrinsic property of antigen: the proteolytic activity of the major mite allergen Der p 1 conditions T cells to produce more IL-4 and less IFN-γ. Eur J Immunol 2001;31:1211–1216. 24 Deb R, Shakib F, Reid K, Clark H: Major house dust mite allergens Der p 1 and Der f 1 degrade and inactivate lung surfactant proteins-A and -D. J Biol Chem 2007; 282: 36808–36819. 25 Ovsyannikova IG, Vailes LD, Li Y, Heymann PW, Chapman MD: Monoclonal antibodies to group II Dermatophagoides spp allergens: murine immune response, epitope analysis, and development of a twosite ELISA. J Allergy Clin Immunol 1994;94: 537–546. 26 Lombardero M, Heymann PW, Platts-Mills TA, Fox JW, Chapman MD: Conformational stability of B cell epitopes on group I and group II Dermatophagoides spp allergens: effect of thermal and chemical denaturation on the binding of murine IgG and human IgE antibodies. J Immunol 1990;144:1353– 1360. 27 Chua KY, Doyle CR, Simpson RJ, Turner KJ, Stewart GA, Thomas WR: Isolation of cDNA coding for the major mite allergen Der p 2 by IgE plaque immunoassay. Int Arch Allergy Appl Immunol 1990; 91: 118– 123. 28 Derewenda U, Li J, Derewenda Z, Dauter Z, Mueller GA, Rule GS, Benjamin DC: The crystal structure of a major dust mite allergen Der p 2, and its biological implications. J Mol Biol 2002;318:189–197. 29 Ichikawa S, Takai T, Yashiki T, Takahashi S, Okumura K, Ogawa H, Kohda D, Hatanaka H: Lipopolysaccharide binding of the mite allergen Der f 2. Genes Cells 2009;14:1055– 1065. 30 Fernández-Caldas E, Iraola V, Carnés J: Molecular and biochemical properties of storage mites (except Blomia species). Protein Pept Lett 2007;14:954–959. 31 Fernández-Caldas E, Iraola Calvo V: Mite allergens. Curr Allergy Asthma Rep 2005;5: 402–410.
32 Smith AM, Benjamin DC, Hozic N, Derewenda U, Smith WA, Thomas WR, Gafvelin G, van Hage-Hamsten M, Chapman MD: The molecular basis of antigenic cross-reactivity between the group 2 mite allergens. J Allergy Clin Immunol 2001;107: 977–984. 33 Luczynska CM, Griffin P, Davies RJ, Topping MD: Prevalence of specific IgE to storage mites (A. siro, L. destructor and T. longior) in an urban population and crossreactivity with the house dust mite (D. pteronyssinus). Clin Exp Allergy 1990; 20: 403–406. 34 van Hage-Hamsten M, Johansson SG, Johansson E, Wiren A: Lack of allergenic cross-reactivity between storage mites and Dermatophagoides pteronyssinus. Clin Allergy 1987;17:23–31. 35 Park JW, Ko SH, Yong TS, Ree HI, Jeoung BJ, Hong CS: Cross-reactivity of Tyrphagus putrescentiae with Dermatophagoides farinae and Dermatophagoides pteronyssinus in urban areas. Ann Allergy Asthma Immunol 1999;83:533–539. 36 Johansson E, Johansson SG, Van HageHamsten M: Allergenic characterization of Acarus siro and Tyrophagus putrescentiae and their crossreactivity with Lepidoglyphus destructor and Dermatophagoides pteronyssinus. Clin Exp Allergy 1994; 24: 743–751. 37 Witteman AM, Akkerdaas JH, van Leeuwen J, van der Zee JS, Aalberse RC: Identification of a cross-reactive allergen (presumably tropomyosin) in shrimp, mite and insects. Int Arch Allergy Immunol 1994;105:56–61. 38 van Ree R, Antonicelli L, Akkerdaas JH, Pajno GB, Barberio G, Corbetta L, Ferro G, Zambito M, Garritani MS, Aalberse RC, Bonifazi F: Asthma after consumption of snails in house-dust-mite-allergic patients: a case of IgE cross-reactivity. Allergy 1996; 51:387–393. 39 Acevedo N, Sánchez J, Erler A, Mercado D, Briza P, Kennedy M, Fernandez A, Gutierrez M, Chua KY, Cheong N, Jiménez S, Puerta L, Caraballo L: IgE cross-reactivity between Ascaris and domestic mite allergens: the role of tropomyosin and the nematode polyprotein ABA-1. Allergy 2009; 64: 1635–1643. 40 Acevedo N, Erler A, Briza P, Puccio F, Ferreira F, Caraballo L: Allergenicity of Ascaris lumbricoides tropomyosin and IgE sensitization among asthmatic patients in a tropical environment. Int Arch Allergy Immunol 2011;154:195–206.
41 Cooper PJ: Interactions between helminth parasites and allergy. Curr Opin Allergy Clin Immunol 2009;9:29–37. 42 Maizels RM: Parasite immunomodulation and polymorphisms of the immune system. J Biol 2009;8:62. 43 Caraballo L, Acevedo N: New allergens of relevance in tropical regions: the impact of Ascaris lumbricoides infections. WAO J 2011;4:77–84. 44 Hagel I, Cabrera M, Hurtado MA, Sanchez P, Puccio F, Di Prisco MC, Palenque M: Infection by Ascaris lumbricoides and bronchial hyper reactivity: an outstanding association in Venezuelan school children from endemic areas. Acta Trop 2007; 103: 231– 241. 45 López N, de Barros-Mazon S, Vilela MM, Condino Neto A, Ribeiro JD: Are immunoglobulin E levels associated with early wheezing? A prospective study in Brazilian infants. Eur Respir J 2002;20:640–645. 46 Tovey E, Ferro A: Time for new methods for avoidance of house dust mite and other allergens. Curr Allergy Asthma Rep 2012;12: 465–477. 47 Tovey ER, Marks GB: It’s time to rethink mite allergen avoidance. J Allergy Clin Immunol 2011;128:723–727. 48 Sears MR, Greene JM, Willan AR, et al: A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med 2003; 349: 1414– 1422. 49 Chen KW, Blatt K, Thomas WR, Swoboda I, Valent P, Valenta R, Vrtala S: Hypoallergenic Der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy. J Allergy Clin Immunol 2012;130:435–443. 50 Spieksma FTM, Spieksma-Boezeman MIA: The mite fauna of house dust with particular reference to the house-dust mite Dermatophagoides pteronyssinus (Trouessart, 1897). Acarologia 1967;9:226–241. 51 Voorhorst R, Spieksma FTM, Varekamp H, Leupen MJ, Lyklema A W: The house-dust mite (Dermatophagoides pteronyssinus) and the allergens it produces: identity with the house-dust allergen. J Allergy 1967; 39: 325–339.
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Dr. Enrique Fernández-Caldas Inmunotek SL Calle Punto Mobi, 5 ES–28805 Alcalá de Henares, Madrid (Spain) E-Mail efcaldas @ inmunotek.com
Mites and Allergy Enrique Fernández-Caldas a, b · Leonardo Puerta c · Luis Caraballo c a Inmunotek SL, Madrid, Spain; b Division of Allergy and Immunology, College of Medicine, University of South Florida, Tampa, Fla., USA; c Institute for Immunological Research, University of Cartagena, Cartagena, Colombia
Allergic diseases triggered by mite allergens include allergic rhinoconjunctivitis, asthma, atopic dermatitis and other skin diseases. Since the early discovery of the allergenic role of mites of the genus Dermatophagoides in the mid 1960s, numerous species have been described as the source of allergens capable of sensitizing and inducing allergic symptoms in sensitized and genetically predisposed individuals. The main sources of allergens in house dust worldwide are the fecal pellets of the mite species D. pteronyssinus, D. farinae, Euroglyphus maynei and the storage mites Blomia tropicalis, Lepidoglyphus destructor and Tyropahgus putrescentiae. Group 1 and 2 allergens are major house dust mite allergens. The main allergens in storage mites include fatty acid-binding proteins, tropomyosin and paramyosin homologues, apolipophorin-like proteins, α-tubulins and others, such as group 2, 5 and 7 allergens. Cross-reactivity is an important and common immunological feature among mites. Currently, purified native or recombinant allergens, epitope mapping, proteomic approaches and T cell proliferation techniques are be-
ing used to assess cross-reactivity. Mites contain potent enzymes capable of degrading a wide range of substrates. Most mite allergens are enzymes. Advances in genomics and molecular biology will improve our ability to understand the genetics of specific IgE responses to mites. Mite allergen avoidance and immunotherapy are the only two allergen-specific ways to treat miteinduced respiratory and cutaneous diseases. © 2014 S. Karger AG, Basel
In 1922, Giocomo R. Ancona (1886–1976) studied 21 mill workers suffering from asthma and realized that the disease was induced by the grain mite, Pediculoides ventricosus [1]. It was novel to establish mites as a possible trigger of asthma and identified a potentially important new source of allergens. Later on, the scientist and physician Willem Storm van Leeuwen (1882–1933; fig. 1) became interested in ‘house-dust asthma’, inspired by publications in the USA. Cooke [2] suggested in 1922 that a specific allergen could be responsible for the allergenicity of house dust. One of the main problems associated Downloaded by: UCONN Storrs 198.143.38.1 - 7/6/2015 8:07:26 PM
Abstract
Fig. 2. Reindert Voorhorst.
with house dust was that skin tests with other allergen extracts often remained negative, but provocations with the dust induced asthma attacks. Storm van Leeuwen indicated that ‘intradermal skin reactions may serve to diagnose the allergic state, but not to make a specific diagnosis. … Doubtless cases of allergy exist which give negative skin tests … with an extract of the allergen which causes the attacks’ [3]. In 1923, Storm van Leeuwen conducted a very special experiment. He went with three asthmatic individuals from the Netherlands to the high mountain area near St. Moritz in Switzerland. Within a few
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Fig. 1. Willem Storm van Leeuwen.
days the asthmatic patients were free of asthma symptoms. However, when the patients inhaled house dust contained in a box and sampled from their flats, they also had exacerbations of their asthma in St. Moritz [4]. It had already been known for many years that asthmatic patients had fewer symptoms in high mountain areas, but now an explanation for the reason had been provided. In 1931, Peipers [5] suggested the presence of numerous allergens in house dust. However, it was not until 1964 that the Dutch group comprised of R. Voorhorst (fig. 2) and the married couple F.T. Spieksma and M.I. Spieksma-Boezeman (fig. 3) demonstrated the presence of house dust mites in dust samples collected in flats in Juliana Street in Leiden, the Netherlands (fig. 4). Mrs. Spieksma-Boezeman was able to demonstrate that mites are the main allergen source in house dust [6]. She also established that there were clearly more mites in the dust from a damp house and that the allergen content was also higher. One of the first appreciations of the new idea of mites as the origin of the house dust allergen came from Jack Pepys [7], as well as from other groups that published confirmative reports [8]. Simultaneously, the Japanese biologist Shiro Oshima, trying to identify parasites causing skin afflictions in schoolchildren in Yokohama, reported the finding of Dermatophagoides species in ‘tatami’ floor coverings [9]. Contact with Japanese colleagues resulted in the first confirming report from countries outside of Europe [10]. Many other scientists and physicians collaborated in the discovery and establishment of house dust mites as one of the most important sources of allergens in house dust worldwide, and we extend our most sincere recognition to them all. Since the early demonstration that dust mites were the origin of the allergenicity of house dust, numerous mite species have been described as the source of allergens capable of sensitizing and inducing allergic symptoms in sensitized and genetically predisposed individuals [11]. The overall treatment of these miteallergic patients focuses primarily on education, the reduction of allergen exposure, pharmacotherapy to reduce allergic inflammation and bronchoconstriction, and immunotherapy. Patients who are exposed to large quantities of mite allergens may experience a
Fig. 3. Family Spieksma: Frits T.M. Spieksma and Marise Spieksma-Boezeman.
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Fig. 4. Bottle with a dust sample collected in 1964 in which mites were detected by Spieksma-Boezeman and Spieksma. The content of the little bottle is a small portion from a mixture of two 5-gram samples of floor dust collected with a vacuum cleaner from the ground floor of a small house in Leiden on October 13, 1964. It was part of a sampling series from three houses with different grades of dampness. The address was Julianastraat 48 and it was the dampest of the three. Samples were taken every 3 weeks. The house does not exist anymore – it was demolished because of poor quality. From the two original 5-gram samples, mites were isolated and counted as described in two published articles [50, 51] and in a personal communication from Frits Spieksma to K.C. Bergmann. Approximately 1,600 mites of the genus Dermatophagoides, almost exclusively D. pteronyssinus, were identified in the sample.
progressive deterioration in PD20FEV1. This fact is consistent with a chronic inflammatory and remodeling process of the lungs, as has been suggested for several animal models, including rhesus monkeys, sheep and mice [12]. There is ample evidence that continuous exposure to mites is an important risk factor for the development of sensitization, allergic respiratory diseases and chronic inflammation of the lungs. Sensitization to house dust mites is a major independent risk factor for asthma in all areas where the climate is conducive to mite population growth. It has been demonstrated that there is a significant dose-response relationship between exposure to mite allergens and subsequent sensitization. Exposure to house dust mite antigen can induce airway epithelial shedding even in subjects with low eosinophil airway infiltration, thus supporting the idea that epithelial damage in asthmatics sensitized to Dermatophagoides may be due to the proteolytic activity of the mite allergens [13]. The most studied species belong to the family Pyroglyphidae, especially D. pteronyssinus, D. farinae and Euroglyphus maynei, and are called house dust mites. House dust mites are commonly present in human dwellings and are especially abundant in mattresses, sofas, carpets and blankets. Numerous mite allergens have been purified, sequenced and cloned. An important group of mites, referred to as
Allergens from House Dust Mites Mite allergens are present in mite bodies, secretion and excretion. Fecal particles contain the greatest proportion of mite allergen [18]. Mite allergens can be detected in many areas of the home, including beds, carpets, upholstered furniture and clothing. Leather-covered couches, wooden furniture and bare floors contain fewer. Beds are the perfect habitat for mites since they provide the ideal temperature, food and moisture for their proliferation, and the allergens they produce accumulate deep inside mattresses and pillows, especially when they are old. Information on the distribution of house dust mites provides valuable information with which to design environmental control strategies. They can also be detected in the air; studies using volumetric samples equipped with sizing devices have shown that mite allergens remain airborne for a short period of time. Allergenic activity has been detected in particles
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smaller than 1 μm and in particles larger than 10 μm. It has been suggested that mite fecal pellets may occasionally enter the lung and cause inflammation and bronchoconstriction [19]. Most of the isolated allergens have been placed in groups based on their chronological characterization and/or homology with previously purified allergens. Purified allergens are named according to the first three letters of the genus, the first letter of the species and a number indicating the group in which they are placed. Thus, the first identified allergen of D. pteronyssinus was named Der p 1 and belongs to group 1. When several isoforms exist they have to be reflected in the denomination, e.g. Der p 1.0101 and Der p 1.0201. The best-studied groups are group 1 (Der p 1 and Der f 1) and group 2 (Der p 2 and Der f 2). They are considered major allergens based on the frequency of patients sensitized and the amount of specific IgE. In Europe, more than 95% of mite-allergic patients are sensitized to Der p 1 and Der p 2. Der p 1 is a glycoprotein with sequence homology and thiol protease functions similar to the enzymes papain, actinidin, bromelain and cathepsins B and H [20]. Der p 1 may upregulate the IgE synthesis by cleaving the low-affinity IgE receptor (CD23) from the surface of human B cell lymphocytes [21]. Der p 1 may also cleave the α-subunit of the interleukin (IL)-2 receptor (IL2R or CD25) from the surface of human peripheral blood T cells and, as a result, these cells show markedly diminished proliferation and interferon-γ secretion, which consequently bias the immune response towards Th2 cells. It has been shown that the cysteine protease activity of Der p 1 seems to selectively enhance the IgE response and that the proteolytic activity of Der p 1 conditions T cells to produce more IL-4 and less interferon-γ [22, 23]. The enzymatic activity for Der p 1 and other mite allergens may also contribute to their immunogenicity by increasing mucosal permeability. Der p 1 and Der f 1 also cleave SP-A and SP-D lung collectins which have protective roles in allergy. The cleavage and consequent inactivation of SP-A and SP-D may be a novel mechanism to account for the potent allergenicity of Der p 1 and Der f 1 [24]. Due to its high prevalence in house dust and worldwide distribution, the group 1 allergen is used as a standard to
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‘storage mites’, mainly comprises members of the Acaridae and Glycyphagidae families that live in stored food and grains. All mite species present in the home environment and capable of inducing immunoglobulin (Ig) E-mediated sensitization are called ‘domestic mites’ [14]. Approximately 150 storage mite species are known [15], and approximately 20 can be considered to be important from an economic and sanitary perspective [16]. The most studied species are Blomia tropicalis, due to its abundance in tropical and subtropical regions of the world [17], and Lepidoglyphus destructor, because of its frequent presence in barns. Storage mite species can be present in kitchen floor dust, cupboards and pantries. In humid homes, storage mites can also be found in mattress dust. They can be an important plague with economical consequences and cause occupational respiratory allergies in farmers and other occupationally exposed individuals. The most important genera are Lepidoglyphus (family Glycyphagidae), Glycyphagus (family Glycyphagidae), Acarus (family Acaridae), Tyrophagus (family Acaridae), Aleuroglyphus (family Acaridae), Suidasia (family Suidasidae), Chortoglyphus (family Chortoglyphidae) and Cheyletus (family Cheyletidae).
Table 1. Biological function, molecular weight (MW) and prevalence of specific IgE binding of several mite allergens [adapted from 50]
Group Biological function
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
MW, kDa
Cysteine protease 25 Niemann-pick type C2 protein 14 Recognition and binding of lipids; similar to MD-2 Trypsin 28 – 30 α-Amylase 57 Unknown 15 Chymotrypsin 25 Lipid-binding protein; similar to pro- 22 – 31 teins in the TLR pathway Glutathione-S-transferase 26 Collagenolytic serine protease 30 Tropomyosin 33 – 37 Paramyosin 92 – 110 Unknown 14 Fatty acid-binding proteins 14 – 15 Lipid-binding apolipophorin 177 Chitinase 98 – 109 Gelsolin-like protein/villin 53 EF-hand calcium-binding protein 53 60-kDa chitinase 60 Antimicrobial peptide 7.2 Arginine kinase 40 Unknown 13.2 Unknown 14 Homology to peritrophin-A domain 14 Troponin C 18
Mite species
IgE binding, %
Dp, Df, Dm, Ds, Em, Bt, As, Ao, Sm, Tp Dp, Df, Dm, Ds, Em, Ld, Gd, Bt, As, Ao, Sm, Tp
70 – 100 80 – 100
Dp, Df, Dm, Ds, Em, Gd, Bt, As, Ao, Sm, Tp Dp, Df, Em, Bt, As, Sm, Tp Dp, Df, Ds, Ld, Gd, Bt, Ao, Sm, Tp Dp, Df, Ds, Bt, Ao, Sm Dp, Df, Ld, Gd, Bt, As, Ao, Sm, Tp
16 – 100 25 – 46 50 – 70 40 50
Dp, Df, Ld, Gd, Bt, As, Ao, Sm Dp, Df, Dm, Bt, Ao, Sm Dp, Df, Ld, Gd, Bt, As, Ao, Sm, Tp, Ca Dp, Df, Dm, Bt Bt Dp, Df, Ld, Gd, Bt, As, Ao, Sm, Tp Dp, Df, Dm, Em, Bt Dp, Df, Dm, Bt Df Df Dp, Df Bt Dp, Df, Ao Dp, Bt Dp, Df, Ao, As, Tp Dp Tp
40 90 50 – 95 80 50 10 – 23 90 70 35 35 50 – 60 10 ? ? ? 74 10.6
Ao = A. ovatus; As = A. siro; Bt = B. tropicalis; Ca = C. arcuatus; Df = D. farinae; Dm = D. microceras; Dp = D. pteronyssinus; Em = E. mayne; Gd = G. domesticus; Ld = L. destructor; Tp = T. putrescentiae; Sm = S. medanensis.
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might be enhanced by a similar interaction. It has been demonstrated that rDer p 2 could act directly on airway smooth muscle cells activating the TLR2 signaling pathway, but not on TLR4. A list containing the most relevant and characterized mite allergens is shown in table 1.
Allergens from Storage Mites Several storage mite allergens have been purified, cloned and sequenced [30]. Some of these allergens can be considered as pan allergens and are present in B. tropicalis, L. destructor, G. domesticus, T. putres-
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estimate environmental exposure to Dermatophagoides spp. in the indoor environment. Der p 2 and Der f 2 are heat- and pH-stable proteins of 14 kDa [25, 26]. These allergens have 88% sequence similarity. In their native stage and expressed as a fusion protein, both have an 83% frequency of specific IgE recognition [27]. Crystallographic studies suggest that Der p 2 is a lipid-binding protein [28]. Der f 2 binds lipopolysaccharide (LPS) in a manner similar to the binding by MD-2. The hydrophobic LPS-binding residues are similar in all of the group 2 allergen sequences [29]. Considering that MD-2 loads LPS onto Toll-like receptor (TLR) 4, it has been suggested that group 2 allergenicity
Family
Species
Glycyphagidae
Glycyphagus domesticus Glycyphagus privatus Gohieria fusca Lepidoglyphus destructor Blomia tropicalis Blomia kulagini Blomia tjibodas Chortoglyphus arcuatus Suidasia medanensis Tyrophagus putrescentiae Tyrophagus longior Acarus siro Acarus farris Thyreophagus entomophagus Aleuroglyphus ovatus Cheyletus eruditus Cheyletus tenuipilis Cheyletus malaccensis
Echimyopodidae Chortoglyphidae Ebertiidae Acaridae
Cheyletidae
centiae, A. siro, A. ovatus, S. medanensis and Thyreophagus entomophagus. Table 2 shows a list of the main families and species of storage mites that have been described as allergenic [31]. Some of these allergens have shown sequence homology and biological function similar to those previously described in Dermatophagoides spp. (see table 1). The main allergens described in storage mites include fatty acidbinding proteins, tropomyosin and paramyosin homologues, apolipophorin-like proteins, α-tubulins and others, such as group 2, 5 and 7 allergens. A list of other mite families and species of allergenic mites, excluding house dust and storage mites, is shown in table 3.
Cross-Reactivity of Mite Allergens Cross-reactivity is a common feature among mite allergens, especially in those from taxonomically related species. Cross-reactivity may also be the cause of mite polysensitization, which is observed in some mite-allergic individuals. Cross-reactivity among group 2 allergens from storage mites, L. destructor, T. putrescentiae and G. domesticus is high, whereas
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Table 3. Other mite families and species of allergenic mites, excluding house dust and storage mites
Family Parasites of plants Predator
Parasites of animals
Species
Tetranychidae
Tetranychus urticae Panonychus ulmi Panonychus citri Tydeidae Pronematus davisi Phytoseiidae Amblyseius cucumeris Phytoseiulus persimilis Hypoaspidae Hypoaspis miles Hemisarcoptidae Hemisarcoptes cooremani Varroaidae Varroa spp. Sarcoptidae Sarcoptes scabiei Analgidae Diplaegidia columbae Ixodidae Ixodes pacificus Ixodes holociclus Ixodes ricinus Riphicephalus spp. Argas reflexus Argasidae
there is only limited cross-inhibition between Der p 2 and the non-pyroglyphid mite allergens. This lack of cross-reactivity between Der p 2 and the group 2 of storage mites is a result of the multiple amino acid substitutions across the surface [32]. Other studies have shown limited cross-reactivity between D. pteronyssinus, L. destructor and T. putrescentiae [33, 34], but others have reported a greater cross-reactivity between Dermatophagoides and T. putresentiae [35]. A low degree of cross-reactivity between D. pteronyssinus, A. siro and T. putrescentiae was described in one study, whereas cross-reactivity between L. destructor and A. siro was high [36]. Individuals allergic to the Dermatophagoides spp. may experience allergic symptoms after eating crustaceans and mollusks. Der f 10 and Der p 10, proteins with homology to tropomyosin from various animals, are involved in the cross-reactivity among Dermatophagoides spp., mollusks and crustaceans. The 36-kDa crossreactive tropomyosin present in mites, various insects (chironomids, mosquitoes and cockroaches) and shrimp [37] is responsible for cross-reactivity among different arthropods [38]. Immunochemical studies have demonstrated that allergens from snails, crustaceans, cockroaches and chironomids cross-re-
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Table 2. Main families and species of storage mites that have been described as allergenic
Effect of Parasitic Infections on Mite Allergy The association of allergy with helminthiases was perceived before the discovery of IgE. However, being able to detect blood levels of this antibody allowed the discovery of the first shared phenotype between ascariasis and asthma: high total IgE levels. This raised the idea that the allergic and anti-parasitic immune responses were similar and, in addition, helminth infections could increase the symptoms of allergy. However, later studies have shown a low prevalence of both allergy and positivity of skin tests (including mites) in areas of great endemicity of helminth infections, suggesting that chronic and high-parasite-load infections induce immunosuppression, an aspect that has been widely documented in recent years although the mechanisms are not fully elucidated [41, 42]. Similarly, in regions with low endemicity where helminth infections are mild-tomoderate and deworming programs are permanent, it has been shown that allergic diseases such as asthma are more common. This is an important historical point since it involves the manifestations of allergy in almost half of the world’s population, among which hygiene conditions are improving progressively, the severity of parasitic infections is diminishing and the prevalence of allergies is increasing, es-
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pecially in urban settings [43]. An important advancement has been made with the description of cross-reactivity between mites and Ascaris allergens [39]. Several scenarios should be considered to explain the immunological interaction between mites and parasites. First, there are many chances of early life exposure to allergens from mites and antigens and A. lumbricoides. This has been observed in children from tropical regions [44, 45]. Second, parasitized preschool and school-aged children in underdeveloped tropical countries receive regular antihelminth drug therapy during mass deworming programs. Since the fundamental socio-economic causes of the infections are not eliminated, children become re-infected several times and this sort of modified secondary immune response may be boosters of the IgE reactivity against cross-reactive allergens from other sources (e.g. mites). Third, mite allergen exposure is perennial and very intense in the tropics; therefore, in the Ascaris-infected population (current or past) susceptible to asthma, this may be another cause of the increasing IgE responses to cross-reactive allergens. To better study the effects of the immune responses to Ascaris on allergy, it is important to identify the molecules that induce allergy symptoms, those that generate a protective IgE immune response and those that promote both effects. A systematic approach to identify the antigens and allergens of A. lumbricoides, inducing immune responses in humans, is needed.
Environmental Control The methods recommended for reducing exposure to house dust mite allergens have not changed much over the last 30 years. The implementation of these methods has provided inconsistent clinical benefit [46], especially in longitudinal prevention studies. However, studies using very strict measures have produced positive results. Evidence that mite allergy is more common in certain countries suggests that there are critical environmental factors which influence the prevalence, incidence and severity of mite-allergic asthma. The main question remains of whether we are able to control or influence these conditions. It is well established that ambient
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act with house dust mite allergens. However, house dust mites are usually the primary source of sensitizing allergens. Tropomyosin is also involved in the cross-reactivity between mites and parasites. A high degree of cross-reactivity between extracts of house dust mites and Ascaris has been demonstrated. Several allergens are implicated, such as tropomyosin and glutathione-S-tranferases [39]. A. lumbricoides tropomyosin (Asc l 3) is an allergen cross-reactive with mite tropomyosins. IgE reactivity to this allergen is very frequent in both asthmatic and normal subjects sensitized to Ascaris [40]. Filarial and mite tropomyosins are similar, with a 72% identity at the amino acid level and overlapping predicted 3D structures. Filarial infection induces strong cross-reactive antitropomyosin antibody responses that may affect sensitization and regulation of allergic reactivity.
humidity and temperature are important factors for the development of mite allergy. Other factors, such as exposure to irritants, adjuvants or substances interacting directly with the innate immune system, remain less clear. The role of allergen exposure in the etiology of allergic sensitization and asthma is very complex [47]. Allergen avoidance is a successful treatment for occupational asthma in many settings and, as such, it should be considered for other occupational or environmental diseases. Although many strategies may reduce allergen levels, its effect in reducing inflammation is not so obvious. Removal of carpets, changing old mite-infested mattresses, pillows and sofas, and improving ventilation are all changes that make sense, but in some cases are not enough to produce a clinical benefit. It is also evident that a successful strategy would be attacking the mite reservoirs with a combination of methods – just one action alone is not enough. Controlling exposure to mite aeroallergens and adjuvant factors seems mandatory.
Mite Immunotherapy Sensitivity and exposure to high levels of mite allergens is an important risk factor for developing and maintaining bronchial hyperreactivity [48]. However, in light of publications that have shown pessimistic results using environmental control measures, immunotherapy with mite extracts has emerged as a solid treatment of mite-induced allergic respiratory diseases. Numerous studies have shown the efficacy of mite sublingual and subcutaneous immunotherapy [12]. The future treatment of mite-induced allergies will not be changed much, although it will be based on a more accurate diagnosis and better immunotherapy treatments. The need to improve the quality of current allergen extracts for diagnosis and treatment is clear [49].
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Mites and Allergy
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Fernández-Caldas · Puerta · Caraballo
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Dr. Enrique Fernández-Caldas Inmunotek SL Calle Punto Mobi, 5 ES–28805 Alcalá de Henares, Madrid (Spain) E-Mail efcaldas @ inmunotek.com
