Cross-sectional study on sensitization to mite and cockroach allergen components in allergy patients in the Central European region

Cross-sectional study on sensitization to mite and cockroach allergen components in allergy... Background: The major sources of allergens in the indoor air include house dust mites, dander derived from domes- tic animals and rodents, cockroach, and several fungi. Mites are the main cause of allergies in some countries with a warmer climate, but the epidemiological significance of mite and cockroach allergens in Central Europe has not been established yet. Methods: We assessed sensitization profiles of allergy patients in a Central European region in regard to sensitization to mites and cockroach. We used molecular diagnosis by means of the microarray ISAC, and we investigated 1766 patients with clinical suspicion to an allergic disorder. 1255 of them were positive to at least one allergen component, and this group was subjected to statistical analysis. Results: The sensitization to at least one mite-specific molecule (Der p 1, 2, Der f 1, 2) was observed relatively fre - quently in 32.7% of patients. Specific IgE to mite group 2 molecules is almost fully cross-reactive. Group 1 allergens are also cross-reactive, but in some patients, a species-specific response was observed. Relatively high rate of sensitization both to group 1 and 2 allergens in our patients indicates the greater role of co-sensitizations. Isolated sensitizations to molecules derived from glyciphagid mites Lep d 2 and/or Blo t 5 without sensitization to other mite-derived mol- ecules were observed only exceptionally (in 0.6% of cases). True sensitization to at least one cockroach-specific mol- ecule (Bla g 1, 2, 5) was very rare (in 0.6% of cases), and nearly all of them were co-sensitizations with other noncock- roach-derived molecules. Sensitization to an inhaled tropomyosin was observed rarely in 2.2% of patients (Der p 10 in 1.9% and Bla g 7 in 1.5%). Co-sensitization of inhaled tropomyosins with the respective mite- or cockroach-specific molecules was observed only in the minority of patients suggesting the different route of sensitization being more frequent. Conclusions: The majority of patients are co-sensitized to several molecules of the respective allergen source. The knowledge of this molecular spectrum of sensitization is important for optimal diagnosis and treatment in respect to allergen content in mite extracts used for diagnostic and therapeutic purposes. In regard to the sensitization patterns of Central European patients, it is necessary to point out the importance of quantifying at least three major mite com- ponents Der f 1, Der p 1 and Der f 2 (or Der p 2). *Correspondence: panzner@fnplzen.cz Department of Immunology and Allergology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Panzner et al. Clin Transl Allergy (2018) 8:19 Page 2 of 9 in the screening of serum IgE-reactivity, and they allow Background the definition of sensitization profiles. Identification of Immediate hypersensitivity to indoor allergens is a risk sensitizations and co-sensitizations to species-specific factor for asthma, and allergic rhinitis and sensitization and cross-reacting allergen components may be espe- to these allergens may play a role in atopic dermatitis cially important in decisions concerning allergen-specific as well. The major sources of allergens in the indoor air immunotherapy. include house dust mite (HDM), dander derived from This study aimed to assess the usefulness of molecu - domestic animals and rodents, cockroach, and several lar diagnosis using a microarray in the description of fungi. Given that most persons in Western societies sensitization profiles in subjects showing a sensitization spend more than 90% of their lives in indoor environ- to HDM and cockroach living in the Central European ments, it is not surprising that indoor allergens play an region, with a special focus on discriminating between important role in allergic sensitization and symptoms. cross-reactivities and multiple sensitizations to differ - Sensitization to distinct molecules may represent higher ent allergens. Although not much data on the diagnostic risk for asthma, or atopic dermatitis [1, 2] and several accuracy of the microarray ImmunoCAP ISAC in HDM studies suggest that sensitization to multiple molecules and cockroach allergy is available, we decided to use this (“molecular spreading”) is associated with a higher prob- approach because of the possibility it provides to analyze ability of more severe symptoms of allergy [2–4]. a wide spectrum of component sensitizations. Further- HDM is the main cause of allergies in some countries more, some studies have shown similar performances for with a warmer climate [5]; in Central Europe, the sensi- component-based microarray ISAC and whole-allergen tization rates to mites, some animals (especially cats and CAP system detection [12, 13]. Nonetheless, it is neces- dogs) and molds (especially Alternaria) immediately fol- sary to bear in mind the possible different sensitivities to low the sensitization rates to pollens [6, 7]. Cockroach individual molecules in the used assay. allergy is an important cause of asthma in several regions of America and Asia [8], its significance in Central Methods Europe has not been established yet. This cross-sectional observational study was conducted While the diagnosis of immunoglobulin E (IgE)-medi- according to the STROBE recommendations [14] to the ated inhalant allergy is primarily based on clinical his- extent which may apply to this study design. We retro- tory and sensitization, that is demonstrated via skin prick spectively analyzed data from 1766 patients who had testing and measurement of serum allergen-specific IgE; been examined in the years 2011–2014 based on suspi- this methodology has its limitations. In vitro and in vivo cion of allergy at the outpatient service of the Depart- allergy testing are often based on, the insufficiency of ment of Immunology and Allergology of the University standardized allergen extracts owing to the natural varia- Hospital in Pilsen; the patients came from the western bility of the allergen source, or manufacturing procedure, part of the Czech Republic. One thousand two hundred can differ regarding their allergenic content. This issue fifty-five patients positive to at least one allergen com - was already confirmed also for HDM allergens [9–11]. An ponent were subjected to further detailed analysis. This even more important disadvantage of allergenic extracts test group of 1255 sensitized patients had at least one of is that they are incapable of differentiating between pri - the following diagnoses: chronic rhinitis (73%), bronchial mary sensitization and immunological cross-reactivity asthma (41%), atopic dermatitis (34%), urticaria or edema in multiple sensitizations which are observed in many (19%), and/or anaphylaxis (11%). Patient ages ranged patients. Nonetheless, natural allergenic extracts were from 1 to 68 years, with a mean age of 29 years. The sex the cornerstone of inhalant allergy diagnosis until several ratio was 45.3% men to 54.7% women. years ago, when the molecular diagnosis was made pos- The detection of specific IgE to multiple allergen com - sible by advances in molecular biology which lead to the ponents was performed using the 112 component Immu- development of a large spectrum of purified natural and noCAP ISAC allergen microarray immunoassay (Thermo recombinant allergenic molecules. Such presently rou- Fisher Scientific, Uppsala, Sweden). Briefly, microarray tinely available reagents enable the use of the diagnostic reaction sites were incubated with 20 μl undiluted patient approach commonly known as a component-resolved serum for 2 h to capture allergen-specific IgE antibodies diagnosis of allergy, and now allow the systematic study by their corresponding allergen. Subsequently, the micro- of the principal allergens and cross-reactivity processes array slides were rinsed and washed to remove unbound involved in allergic sensitization. sIgE. After drying, complexes of allergen-bound sIgE The introduction of microarrays with a much larger were stained with a secondary, fluorescence-labeled anti- number of purified or recombinant molecules consti - human IgE for 1  h at room temperature while protected tuted a further development in the diagnosis of allergic from light. After a second rinsing and washing procedure, diseases. Such microarrays now represent powerful tools Panzner et al. Clin Transl Allergy (2018) 8:19 Page 3 of 9 the obtained fluorescence signals were scanned using In patients sensitized to Der p 10 and not to Bla g 7 a laser scanner (LuxScan 10K; CapitalBio, Beijing, (0.6%) no sensitization to other tropomyosins (Pen m 1, China). Analysis of the corresponding digitized micro- Ani s 3) was observed in nearly all of the cases (0.5%), array images was performed using ImmunoCAP ISAC and sensitization to other mite-derived molecules was software, and image information was transformed into observed only in 0.2% of cases. In patients sensitized numerical data according to a reference serum of known both to Der p 10 and Bla g 7 (1.3%), sensitization to other IgE content. Results were expressed as ISAC standard- tropomyosins was observed in all cases, and sensitization ized units (ISU), and values greater than or equal to 0,3 to other mite-derived molecules was observed in 0.5% of ISU/l were taken as positive. cases. Monosensitization (in the frame of tropomyosins) The analysis was focused on inhalant mite- and cock - to Bla g 7 was only exceptional. roach-derived specific allergen components and poten - The frequency of sensitization to individual mite- tially cross-reactive components which are included derived molecules, and their co-sensitizations is shown in the ISAC system. Specific allergy markers are repre - in Figs.  1 and 2. Sensitizations and co-sensitizations in sented by the group 1 (nDer p 1, nDer f 1), group 2 (rDer the frame of tropomyosins and mites are shown in Fig. 3. p 2, rDer f 2, rLep d 2) and group 5/21 (rBlo t 5) allergens The sensitization to mite-specific molecules in the con - for mites, and molecule rBla g 1, aspartic protease rBla text of sensitizations to molecules specific for other g 2 and glutathione-S-transferase rBla g 5 for cockroach. inhalant allergens is shown in Fig. 4. Finally, panallergens like mite- and cockroach-derived tropomyosins (rDer p 10 and nBla g 7) were also included Discussion in the analysis and related to sensitizations to other tro- The observed sensitization rate to perennial inhalant- pomyosins (nPen m 1 and rAni s 3). derived molecules in our group of patients is lower than the sensitization rate to pollen-derived components [6]. Results However, the relatively high sensitization rate to mites The results of the analysis describing the HDM and cock - underlines their clinical importance in the Central Euro- roach sensitization patterns in the group of 1255 patients pean region. It needs to be emphasized that in this paper sensitized to at least one allergen component in our we focus only on sensitization rates and not their clinical region are listed below. All percentages were calculated relevance; carrying out the latter analysis without using using the whole group of 1255 patients. specific provocation tests might become rather compli - cated and is not realistic in such large cohorts. Mites The sensitization to at least one mite-specific molecule Cockroach (Der p 1, 2, Der f 1, 2) was observed in 32.7% of patients. It has been suggested that a cocktail of five allergens Bla Isolated sensitizations to molecules derived from glyci- g 1 and/or Per a 1, Bla g 2, Bla g 4, Bla g 5, and Bla g 7 phagid mites Lep d 2 and/or Blo t 5 without sensitization and/or Per a 7 would be expected to diagnose 50–64% to other mite-derived molecules were observed only in of cockroach-allergic patients [15, 16]. The degree of 0.6% of cases. homology between the lipocalin Bla g 4 and the mamma- lian lipocalins is low, and only small cross-reactivity with Cockroach these mammalian allergens would be expected [8]. We True sensitization to at least one cockroach-specific mol - did not analyze this cross-reactivity because of the very ecule (Bla g 1, 2, 5) was very rare (in 0.6% of cases), and low rate of sensitization to Bla g 4 in our patients. The nearly all of them were co-sensitizations with other non- low rate of sensitization to cockroach-derived molecules cockroach-derived molecules, including mite-derived was caused probably rather by the low presence of cock- molecules in half of the patients (4 cases). roaches in our climate than by missing molecules in the used assay. Tropomyosins Sensitization to an inhaled mite- and cockroach-derived Mites tropomyosin was observed in 2.2% of patients (Der p 10 According to several studies, HDM sensitization and in 1.9% and Bla g 7 in 1.5%). allergy are considered to be the most frequent among Co-sensitization of Der p 10 with other mite-derived inhalant allergies [5, 17, 18]. In our conditions, it holds molecules was observed in 0.7% of patients. Co-sensiti- the fourth position behind grass pollen (sensitization fre- zation of Bla g 7 with other cockroach-specific molecules quency for Phl p 1 is 60.8%), birch pollen (sensitization was exceptional (in 0.1%), without co-sensitization to Der frequency for Bet v 1 is 47.3%), and cat allergens (sensi- p 10 in all cases. tization frequency for Fel d 1 is 31.5%) [6], what differs Panzner et al. Clin Transl Allergy (2018) 8:19 Page 4 of 9 25.7% 25.1% 23.5% 23.5% IgE levels 0.3-0.9.ISU 1.0-14.9 ISU 19.0% 18.7% ≥ 15.0 ISU 17.2% 17.1% 10.8% 10.0% 6.1% 5.0% 5.0% 3.6% 3.3% 1.9% 2.7% 1.5% 0.7% 0.5% 0.1% Der p 1Der p 2Der f 1Der f 2Lep d 2Blo t 5Der p 10 Fig. 1 Sensitization rates to mite-derived molecules Fig. 2 Venn diagram depicting mono- and co-sensitizations to mite-derived molecules. Mono- and co-sensitizations with a frequency of less than 0.6% are not shown Panzner et al. Clin Transl Allergy (2018) 8:19 Page 5 of 9 Fig. 3 Venn diagram depicting mono- and co-sensitizations to tropomyosins in relation to sensitization to mites (= sensitization to at least one mite-specific molecule). Mono- and co-sensitizations with a frequency of less than 0.2% are not shown from data coming from other regions [17, 19, 20]. This group 1 allergens in the onset of sensitization, perhaps discrepancy may be caused by geographical differences or mediated by their proteolytic activity and direct epi- may be due to the selected population, mainly consisting thelial damage [27]. The more frequent sensitization to of adults with predominant respiratory allergy. Higher group 2 allergens in the adult population suggested a sensitization rate to grass pollen in adolescents was also later sensitization to group 1 allergens what was docu- shown in a study from northern Italy while the leading mented by observation of a birth cohort [26]. The abil - position of mites was pronounced clearly in smaller chil- ity of group 2 allergens to bind directly to TLR4 might dren [19]. be an explanation for this observation. These facts may It is known that patients sensitized to mites are not also explain that in the case of mites the higher the always sensitized to the molecules used in our study, exposure, the more severe the clinical allergic condi- other molecules may also play a role, but the number tion, in contrast to cat allergens where overexposure of patients sensitized only to these other molecules is seems to lead to tolerance [28]. generally very low [21–25]. Moreover, cysteine pro- Dermatophagoides pteronyssinus is the most wide- tease (Der p 1, Der f 1) signaling has been described spread mite all over the world; it predominates especially to have a strong TH2 up-regulation effect, and group in humid regions where the climate is more influenced 2 allergens have been shown to bind TLR4 via binding by the ocean. Dermatophagoides farinae is supposed LPS, thus having a stronger immunogenic potential fur- to occur more in the continental regions of Europe and ther enhancing the complexity of mite allergy. Hence, the Mediterranean area, but most countries have mixed these molecules may play a leading role in the atopic populations [22, 29]. In our patients, sensitization to D. march, and a differential sensitization rate in children pteronyssinus and D. farinae was almost equal in contrast compared to adults may be present [26]. Sensitization to Spain where the IgE-prevalence to D. pteronyssinus to group 1 allergens was shown to be more frequent allergens was found to be slightly higher than to D. fari- in children [18], thereby suggesting a possible role of nae allergens [18]. Panzner et al. Clin Transl Allergy (2018) 8:19 Page 6 of 9 Fig. 4 Venn diagram depicting mono- and co-sensitizations to different groups of molecules—mites and other inhalant allergens. Sensitization to a group is defined as sensitization to at least one of the respective species-specific component: mites (Der p 1, Der p 2, Der f 1, Der f 2), cat (Fel d 1, Fel d 4), dog (Can f 1, Can f 2, Can f 5), horse (Equ c 1), Alternaria (Alt a 1, Alt a 6), pollens (Phl p 1, Phl p 2, Phl p 4, Phl p 5, Phl p 6, Phl p 11, Cyn d 1, Bet v 1, Aln g 1, Cor a 1, Cup a 1, Cry j 1, Ole e 1, Ole e 9, Pla a 2, Pla l 1, Art v 1, Che a 1). Mono- and co-sensitizations with a frequency of less than 1.0% are not shown Although the pyroglyphid HDM D. pteronyssinus and levels of sensitization to Blo t 5 in our group. The results D. farinae seem to predominate, glyciphagid mites may of another study suggested that allergens different from also be important in some regions [18, 21, 29]. those belonging to group 5 may also be responsible for Blomia tropicalis is the most important house dust the partial cross-reactivity among different mite species mite from the family glycyphagidae. It is most abun- [30]. dant in tropical regions [4, 29]. The major allergen Blo Lepidoglyphus destructor, a glycyphagid storage mite, t 5 shows 40% sequence homology with Der p 5, but it may also become a HDM [29]. Sensitization from domes- was reported not to cross-react with each other [29]. tic exposure was reported from Sweden and France. It is As B. tropicalis does not form part of the acarofauna in not possible to decide whether positivity to Lep d 2 in our Central Europe, the not negligible sensitization rate in patients was due to true sensitization or cross-reactivity our patients seems to be attributable rather to potential within mite group 2 molecules. The absence of mono- cross-reactivity among allergens produced by different sensitizations to Lep d 2 (in the frame of mite-derived mite species (mite group 5/21 molecules) than to true molecules) in our patients testifies rather for Lep d 2 sensitization. This assumption is also supported by low sensitization due to cross-reactivity with other group 2 Panzner et al. Clin Transl Allergy (2018) 8:19 Page 7 of 9 allergens, what is in contradiction to the data suggesting allergens in our patients indicates the greater role of that no such cross-reactivity exists [18]. co-sensitizations. Mite sensitized patients in our group were usually co- sensitized to several mite-specific components; mono - Conclusions sensitization was markedly less frequent (Fig.  2). Der f The vast majority of mite-sensitized patients in our 1 and Der p 1 (cysteine proteases) and Der f 2 and Der group showed polysensitization to two or more com- p 2 (lipid binding proteins) are assumed to be the spe- ponents derived from both major HDM, i.e., D. pteron- cific components most commonly involved in mite yssinus and D. farinae. On the contrary, only a minority allergy. The predominant sensitization, both regard - was sensitized to mite-derived tropomyosin, and these ing prevalence and intensity, to mite group 2 molecules sensitizations were not frequently connected to sensitiza- was already described [17, 18, 25] and confirmed by our tion to other mite-derived molecules, suggesting domi- results. In a French study, predominant sensitization to nating different route of sensitization via food-derived Der p 1 (93%) was detected [31], and we may speculate tropomyosins. that this difference might be due to the different popu - It is necessary to stress the importance of the knowl- lation studied. The same French study also detected a edge of allergen content in mite extracts used for higher frequency of sensitization to Der p 10 (28%) sign- diagnostic and therapeutic purposes as a practical impli- aling the primary sensitizing agent possibly being shrimp cation from this study. Several studies have focused on which is much more consumed in the Mediterranean this issue and analyzed the composition of several com- area than in Central Europe. mercially available preparations concerning their quali- Tropomyosins are molecules responsible for cross- tative and quantitative allergen composition. There are reactivity among mites, shrimp, and cockroach [32]. IgE evident considerable differences in the allergen con - binding to the mite group 10 allergens is rare in Europe tent among the commercially available extracts [9–11]. [21] and Australia [33] and, from one study, in US sub- Although some authors question the necessity of tailor- jects allergic to both HDM and cockroach [34]. Similarly, ing of allergen immunotherapy to the sensitizing species in this study’s population group, sensitization to indi- [22], we consider this to be important for the optimal vidual tropomyosins was considerably less frequent than efficacy of this treatment. Group 2 allergens are highly sensitization to more tropomyosin molecules together cross-reactive, but as group 1 sensitization could be spe- suggesting present cross-reactivity in the frame of this cies specific in some patients and its prevalence is higher group of molecules (Fig. 3). in children, an adequate balance of major mite species Sensitization to the tropomyosin Der p 10 was not and major allergens must be considered in the design of observed frequently (in 1.9%) in our patients, and co- mite allergy vaccines. Regarding the sensitization pat- sensitizations with other mite-specific molecules were terns of patients within the Central European region, not regular (in 0.8%) suggesting the possible different it is necessary to point out the importance of quantify- route of sensitization in a considerable proportion of ing at least three major mite components Der f 1, Der p the patients. Tropomyosins represent clinically relevant 1 and Der f 2 (or Der p 2). Such information is crucial seafood allergens, but the role of mite tropomyosin, Der for effective diagnosis and treatment. Besides these mol - p 10, in house dust mite allergy has not been studied in ecules, Der p 23, a new major house dust mite allergen, detail. A hypothesis that tropomyosin sensitization may should be considered to be an important component for indicate a true food allergy independent of mite respira- allergen-specific immunotherapy as well [26, 36, 37]. The tory disease has been proposed [18]. Another hypothesis importance of eventual further allergens (so-called “mid- pretends that Der p 10 may be a diagnostic marker for tier” allergens—e.g., Der p 5) in this context has yet to be mite-allergic patients with additional sensitization to elucidated. There is an urgent need for rigorous, long- allergens other than Der p 1 and Der p 2. Such patients term clinical trials with an efficacy criterion to find the may require attention when allergen-specific immuno - consensus on the dose of individual molecules in HDM- therapy is considered [35]. allergen-specific immunotherapy [37, 38]. The high rate of simultaneous sensitizations to differ - ent mite components (Fig.  2) may be explained either by co-sensitizations or by cross-reactivities. Specific IgE Abbreviations HDM: house dust mite; IgE: immunoglobulin E; ISAC: immuno solid-phase to Der p 2/Der f 2 is almost fully cross-reactive, but no allergen chip; STROBE: strengthening the reporting of observational studies in cross-reactivity was described with Lep d 2 [18]. Group epidemiology; LPS: lipopolysaccharide. 1 allergens are also cross-reactive, but in some patients, Authors’ contributions a species-specific response was observed [18]. Rela - PP participated in study design, data analysis, and manuscript writing. tively high rate of sensitization both to group 1 and 2 MV participated in study design, data analysis, and manuscript writing. TV Panzner et al. Clin Transl Allergy (2018) 8:19 Page 8 of 9 participated in laboratory analyses, anonymization of the data, and critical 7. Stemeseder T, Klinglmayr E, Moser S, Lueftenegger L, Lang R, Himly M, revision of the manuscript. PV participated in data analysis and critical revision et al. Cross-sectional study on allergic sensitization of Austrian adoles- of the manuscript. PB participated in data analysis and critical revision of the cents using molecule-based IgE profiling. Allergy. 2017;72(5):754–63. manuscript. MM participated in data analysis, statistical calculations, and 8. Pomes A, Arruda LK. Investigating cockroach allergens: aiming to critical revision of the manuscript. All authors read and approved the final improve diagnosis and treatment of cockroach allergic patients. Meth- manuscript. ods. 2014;66(1):75–85. 9. Casset A, Mari A, Purohit A, Resch Y, Weghofer M, Ferrara R, et al. Varying Author details allergen composition and content affects the in vivo allergenic activity of Department of Immunology and Allergology, Faculty of Medicine in Pilsen, commercial Dermatophagoides pteronyssinus extracts. Int Arch Allergy Charles University, Pilsen, Czech Republic. Department of Immunology Immunol. 2012;159(3):253–62. and Allergology, Faculty Hospital in Pilsen, Pilsen, Czech Republic. Depart- 10. Takai T, Okamoto Y, Okubo K, Nagata M, Sakaguchi M, Fukutomi Y, et al. ment of Dermatovenerology, Faculty Hospital in Pilsen, Pilsen, Czech Republic. Japanese Society of Allergology task force report on standardization of The National Institute of Public Health, Prague, Czech Republic. house dust mite allergen vaccines—secondary publication. Allergol Int. 2015;64(2):181–6. Acknowledgements 11. Brunetto B, Tinghino R, Braschi MC, Antonicelli L, Pini C, Iacovacci P. Support to this article has been provided by the EAACI National Society Com- Characterization and comparison of commercially available mite extracts mittee Support Initiative. The authors wish to thank the EAACI NASC for that. for in vivo diagnosis. Allergy. 2010;65(2):184–90. 12. Melioli G, Bonifazi F, Bonini S, Maggi E, Mussap M, Passalacqua G, et al. Competing interests The ImmunoCAP ISAC molecular allergology approach in adult multi- The authors declare that they have no competing interests. sensitized Italian patients with respiratory symptoms. Clin Biochem. 2011;44(12):1005–11. Availability of data and materials 13. Huss-Marp J, Gutermuth J, Schaffner I, Darsow U, Pfab F, Brockow K, et al. Anonymized source data used for the statistical analysis are available at the Comparison of molecular and extract-based allergy diagnostics with Department of Immunology and Allergology of the Faculty of Medicine in multiplex and singleplex analysis. Allergo J Int. 2015;24:46–53. Pilsen. These data are available from the corresponding author on reasonable 14. Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, request. Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med. Consent for publication 2007;4(10):e297. Not applicable. 15. Barbosa MC, Santos AB, Ferriani VP, Pomes A, Chapman MD, Arruda LK. Efficacy of recombinant allergens for diagnosis of cockroach allergy Ethics approval and consent to participate in patients with asthma and/or rhinitis. Int Arch Allergy Immunol. The study was approved by the Ethics Committee of the Faculty Hospital in 2013;161(3):213–9. Pilsen on 6th October 2016 with reference number 404/2016. Data have been 16. Arruda LK, Barbosa MC, Santos AB, Moreno AS, Chapman MD, Pomes A. anonymized before the analysis. Recombinant allergens for diagnosis of cockroach allergy. Curr Allergy Asthma Rep. 2014;14(4):428. Funding 17. Scala E, Alessandri C, Bernardi ML, Ferrara R, Palazzo P, Pomponi D, et al. The study was funded from internal sources of Faculty of Medicine in Pilsen Cross-sectional survey on immunoglobulin E reactivity in 23,077 subjects and Faculty Hospital in Pilsen. No funding was received from any external using an allergenic molecule-based microarray detection system. Clin sources. Exp Allergy. 2010;40(6):911–21. 18. Barber D, Arias J, Boquete M, Cardona V, Carrillo T, Gala G, et al. Analysis of mite allergic patients in a diverse territory by improved diagnostic tools. Publisher’s Note Clin Exp Allergy. 2012;42(7):1129–38. Springer Nature remains neutral with regard to jurisdictional claims in pub- 19. Melioli G, Marcomini L, Agazzi A, Bazurro G, Tosca M, Rossi GA, et al. The lished maps and institutional affiliations. IgE repertoire in children and adolescents resolved at component level: a cross-sectional study. Pediatr Allergy Immunol. 2012;23(5):433–40. Received: 6 December 2017 Accepted: 23 April 2018 20. Westritschnig K, Sibanda E, Thomas W, Auer H, Aspock H, Pittner G, et al. Analysis of the sensitization profile towards allergens in central Africa. Clin Exp Allergy. 2003;33(1):22–7. 21. Pittner G, Vrtala S, Thomas WR, Weghofer M, Kundi M, Horak F, et al. Com- ponent-resolved diagnosis of house-dust mite allergy with purified natu- References ral and recombinant mite allergens. Clin Exp Allergy. 2004;34(4):597–603. 1. Banerjee S, Resch Y, Chen KW, Swoboda I, Focke-Tejkl M, Blatt K, et al. Der 22. Thomas WR. House dust allergy and immunotherapy. Hum Vaccin Immu- p 11 is a major allergen for house dust mite-allergic patients suffering nother. 2012;8(10):1469–78. from atopic dermatitis. J Invest Dermatol. 2015;135(1):102–9. 23. Hales BJ, Elliot CE, Chai LY, Pearce LJ, Tipayanon T, Hazell L, et al. Quantita- 2. Resch Y, Michel S, Kabesch M, Lupinek C, Valenta R, Vrtala S. Different IgE tion of IgE binding to the chitinase and chitinase-like house dust mite recognition of mite allergen components in asthmatic and nonasthmatic allergens Der p 15 and Der p 18 compared to the major and mid-range children. J Allergy Clin Immunol. 2015;136(4):1083–91. allergens. Int Arch Allergy Immunol. 2013;160(3):233–40. 3. Custovic A, Sonntag HJ, Buchan IE, Belgrave D, Simpson A, Prosperi MC. 24. Weghofer M, Grote M, Resch Y, Casset A, Kneidinger M, Kopec J, et al. Evolution pathways of IgE responses to grass and mite allergens through- Identification of Der p 23, a peritrophin-like protein, as a new major Der - out childhood. J Allergy Clin Immunol. 2015;136(6):1645–52. matophagoides pteronyssinus allergen associated with the peritrophic 4. Kidon MI, Chiang WC, Liew WK, Ong TC, Tiong YS, Wong KN, et al. matrix of mite fecal pellets. J Immunol. 2013;190(7):3059–67. Mite component-specific IgE repertoire and phenotypes of allergic 25. Thomas WR. Hierarchy and molecular properties of house dust mite disease in childhood: the tropical perspective. Pediatr Allergy Immunol. allergens. Allergol Int. 2015;64(4):304–11. 2011;22(2):202–10. 26. Posa D, Perna S, Resch Y, Lupinek C, Panetta V, Hofmaier S, et al. Evolution 5. Bousquet PJ, Chinn S, Janson C, Kogevinas M, Burney P, Jarvis D, et al. and predictive value of IgE responses toward a comprehensive panel of Geographical variation in the prevalence of positive skin tests to envi- house dust mite allergens during the first 2 decades of life. J Allergy Clin ronmental aeroallergens in the European Community Respiratory Health Immunol. 2017;139(2):541–9. Survey I. Allergy. 2007;62(3):301–9. 27. Takai T, Ikeda S. Barrier dysfunction caused by environmental proteases in 6. Panzner P, Vachova M, Vitovcova P, Brodska P, Vlas T. A comprehensive the pathogenesis of allergic diseases. Allergol Int. 2011;60(1):25–35. analysis of middle-European molecular sensitization profiles to pollen 28. Renand A, Archila LD, McGinty J, Wambre E, Robinson D, Hales BJ, allergens. Int Arch Allergy Immunol. 2014;164(1):74–82. et al. Chronic cat allergen exposure induces a TH2 cell-dependent Panzner et al. Clin Transl Allergy (2018) 8:19 Page 9 of 9 IgG4 response related to low sensitization. J Allergy Clin Immunol. 34. Satinover SM, Reefer AJ, Pomes A, Chapman MD, Platts-Mills TAE, Wood- 2015;136(6):1627–35. folk JA. Specific IgE and IgG antibody-binding patterns to recombinant 29. Thomas WR. Geography of house dust mite allergens. Asian Pac J Allergy cockroach allergens. J Allergy Clin Immunol. 2005;115(4):803–9. Immunol. 2010;28(4):211–24. 35. Resch Y, Weghofer M, Seiberler S, Horak F, Scheiblhofer S, Linhart B, 30. Simpson A, Green R, Custovic A, Woodcock A, Arruda LK, Chapman MD. et al. Molecular characterization of Der p 10: a diagnostic marker Skin test reactivity to natural and recombinant Blomia and Dermatopha- for broad sensitization in house dust mite allergy. Clin Exp Allergy. goides spp. allergens among mite allergic patients in the UK. Allergy. 2011;41(10):1468–77. 2003;58(1):53–6. 36. Mueller GA, Randall TA, Glesner J, Pedersen LC, Perera L, Edwards LL, et al. 31. Bronnert M, Mancini J, Birnbaum J, Agabriel C, Liabeuf V, Porri F, et al. Serological, genomic and structural analyses of the major mite allergen Component-resolved diagnosis with commercially available D. pteronys- Der p 23. Clin Exp Allergy. 2016;46(2):365–76. sinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite 37. Batard T, Baron-Bodo V, Martelet A, Le Mignon M, Lemoine P, Jain K, et al. allergy. Clin Exp Allergy. 2012;42(9):1406–15. Patterns of IgE sensitization in house dust mite-allergic patients: implica- 32. Ayuso R, Reese G, Leong-Kee S, Plante M, Lehrer SB. Molecular basis of tions for allergen immunotherapy. Allergy. 2016;71(2):220–9. arthropod cross-reactivity: IgE-binding cross-reactive epitopes of shrimp, 38. Calderon M, Casale T, Nelson H, Demoly P. An evidence-based analysis of house dust mite and cockroach tropomyosins. Int Arch Allergy Immunol. house dust mite allergen immunotherapy: a call for more rigorous clinical 2002;129(1):38–48. studies. J Allergy Clin Immunol. 2013;132(6):1322–36. 33. Hales BJ, Martin AC, Pearce LJ, Laing IA, Hayden CM, Goldblatt J, et al. IgE and IgG anti-house dust mite specificities in allergic disease. J Allergy Clin Immunol. 2006;118(2):361–7. Ready to submit your research ? 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Cross-sectional study on sensitization to mite and cockroach allergen components in allergy patients in the Central European region

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Medicine & Public Health; Allergology; Immunology; Pneumology/Respiratory System
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Abstract

Background: The major sources of allergens in the indoor air include house dust mites, dander derived from domes- tic animals and rodents, cockroach, and several fungi. Mites are the main cause of allergies in some countries with a warmer climate, but the epidemiological significance of mite and cockroach allergens in Central Europe has not been established yet. Methods: We assessed sensitization profiles of allergy patients in a Central European region in regard to sensitization to mites and cockroach. We used molecular diagnosis by means of the microarray ISAC, and we investigated 1766 patients with clinical suspicion to an allergic disorder. 1255 of them were positive to at least one allergen component, and this group was subjected to statistical analysis. Results: The sensitization to at least one mite-specific molecule (Der p 1, 2, Der f 1, 2) was observed relatively fre - quently in 32.7% of patients. Specific IgE to mite group 2 molecules is almost fully cross-reactive. Group 1 allergens are also cross-reactive, but in some patients, a species-specific response was observed. Relatively high rate of sensitization both to group 1 and 2 allergens in our patients indicates the greater role of co-sensitizations. Isolated sensitizations to molecules derived from glyciphagid mites Lep d 2 and/or Blo t 5 without sensitization to other mite-derived mol- ecules were observed only exceptionally (in 0.6% of cases). True sensitization to at least one cockroach-specific mol- ecule (Bla g 1, 2, 5) was very rare (in 0.6% of cases), and nearly all of them were co-sensitizations with other noncock- roach-derived molecules. Sensitization to an inhaled tropomyosin was observed rarely in 2.2% of patients (Der p 10 in 1.9% and Bla g 7 in 1.5%). Co-sensitization of inhaled tropomyosins with the respective mite- or cockroach-specific molecules was observed only in the minority of patients suggesting the different route of sensitization being more frequent. Conclusions: The majority of patients are co-sensitized to several molecules of the respective allergen source. The knowledge of this molecular spectrum of sensitization is important for optimal diagnosis and treatment in respect to allergen content in mite extracts used for diagnostic and therapeutic purposes. In regard to the sensitization patterns of Central European patients, it is necessary to point out the importance of quantifying at least three major mite com- ponents Der f 1, Der p 1 and Der f 2 (or Der p 2). *Correspondence: panzner@fnplzen.cz Department of Immunology and Allergology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Panzner et al. Clin Transl Allergy (2018) 8:19 Page 2 of 9 in the screening of serum IgE-reactivity, and they allow Background the definition of sensitization profiles. Identification of Immediate hypersensitivity to indoor allergens is a risk sensitizations and co-sensitizations to species-specific factor for asthma, and allergic rhinitis and sensitization and cross-reacting allergen components may be espe- to these allergens may play a role in atopic dermatitis cially important in decisions concerning allergen-specific as well. The major sources of allergens in the indoor air immunotherapy. include house dust mite (HDM), dander derived from This study aimed to assess the usefulness of molecu - domestic animals and rodents, cockroach, and several lar diagnosis using a microarray in the description of fungi. Given that most persons in Western societies sensitization profiles in subjects showing a sensitization spend more than 90% of their lives in indoor environ- to HDM and cockroach living in the Central European ments, it is not surprising that indoor allergens play an region, with a special focus on discriminating between important role in allergic sensitization and symptoms. cross-reactivities and multiple sensitizations to differ - Sensitization to distinct molecules may represent higher ent allergens. Although not much data on the diagnostic risk for asthma, or atopic dermatitis [1, 2] and several accuracy of the microarray ImmunoCAP ISAC in HDM studies suggest that sensitization to multiple molecules and cockroach allergy is available, we decided to use this (“molecular spreading”) is associated with a higher prob- approach because of the possibility it provides to analyze ability of more severe symptoms of allergy [2–4]. a wide spectrum of component sensitizations. Further- HDM is the main cause of allergies in some countries more, some studies have shown similar performances for with a warmer climate [5]; in Central Europe, the sensi- component-based microarray ISAC and whole-allergen tization rates to mites, some animals (especially cats and CAP system detection [12, 13]. Nonetheless, it is neces- dogs) and molds (especially Alternaria) immediately fol- sary to bear in mind the possible different sensitivities to low the sensitization rates to pollens [6, 7]. Cockroach individual molecules in the used assay. allergy is an important cause of asthma in several regions of America and Asia [8], its significance in Central Methods Europe has not been established yet. This cross-sectional observational study was conducted While the diagnosis of immunoglobulin E (IgE)-medi- according to the STROBE recommendations [14] to the ated inhalant allergy is primarily based on clinical his- extent which may apply to this study design. We retro- tory and sensitization, that is demonstrated via skin prick spectively analyzed data from 1766 patients who had testing and measurement of serum allergen-specific IgE; been examined in the years 2011–2014 based on suspi- this methodology has its limitations. In vitro and in vivo cion of allergy at the outpatient service of the Depart- allergy testing are often based on, the insufficiency of ment of Immunology and Allergology of the University standardized allergen extracts owing to the natural varia- Hospital in Pilsen; the patients came from the western bility of the allergen source, or manufacturing procedure, part of the Czech Republic. One thousand two hundred can differ regarding their allergenic content. This issue fifty-five patients positive to at least one allergen com - was already confirmed also for HDM allergens [9–11]. An ponent were subjected to further detailed analysis. This even more important disadvantage of allergenic extracts test group of 1255 sensitized patients had at least one of is that they are incapable of differentiating between pri - the following diagnoses: chronic rhinitis (73%), bronchial mary sensitization and immunological cross-reactivity asthma (41%), atopic dermatitis (34%), urticaria or edema in multiple sensitizations which are observed in many (19%), and/or anaphylaxis (11%). Patient ages ranged patients. Nonetheless, natural allergenic extracts were from 1 to 68 years, with a mean age of 29 years. The sex the cornerstone of inhalant allergy diagnosis until several ratio was 45.3% men to 54.7% women. years ago, when the molecular diagnosis was made pos- The detection of specific IgE to multiple allergen com - sible by advances in molecular biology which lead to the ponents was performed using the 112 component Immu- development of a large spectrum of purified natural and noCAP ISAC allergen microarray immunoassay (Thermo recombinant allergenic molecules. Such presently rou- Fisher Scientific, Uppsala, Sweden). Briefly, microarray tinely available reagents enable the use of the diagnostic reaction sites were incubated with 20 μl undiluted patient approach commonly known as a component-resolved serum for 2 h to capture allergen-specific IgE antibodies diagnosis of allergy, and now allow the systematic study by their corresponding allergen. Subsequently, the micro- of the principal allergens and cross-reactivity processes array slides were rinsed and washed to remove unbound involved in allergic sensitization. sIgE. After drying, complexes of allergen-bound sIgE The introduction of microarrays with a much larger were stained with a secondary, fluorescence-labeled anti- number of purified or recombinant molecules consti - human IgE for 1  h at room temperature while protected tuted a further development in the diagnosis of allergic from light. After a second rinsing and washing procedure, diseases. Such microarrays now represent powerful tools Panzner et al. Clin Transl Allergy (2018) 8:19 Page 3 of 9 the obtained fluorescence signals were scanned using In patients sensitized to Der p 10 and not to Bla g 7 a laser scanner (LuxScan 10K; CapitalBio, Beijing, (0.6%) no sensitization to other tropomyosins (Pen m 1, China). Analysis of the corresponding digitized micro- Ani s 3) was observed in nearly all of the cases (0.5%), array images was performed using ImmunoCAP ISAC and sensitization to other mite-derived molecules was software, and image information was transformed into observed only in 0.2% of cases. In patients sensitized numerical data according to a reference serum of known both to Der p 10 and Bla g 7 (1.3%), sensitization to other IgE content. Results were expressed as ISAC standard- tropomyosins was observed in all cases, and sensitization ized units (ISU), and values greater than or equal to 0,3 to other mite-derived molecules was observed in 0.5% of ISU/l were taken as positive. cases. Monosensitization (in the frame of tropomyosins) The analysis was focused on inhalant mite- and cock - to Bla g 7 was only exceptional. roach-derived specific allergen components and poten - The frequency of sensitization to individual mite- tially cross-reactive components which are included derived molecules, and their co-sensitizations is shown in the ISAC system. Specific allergy markers are repre - in Figs.  1 and 2. Sensitizations and co-sensitizations in sented by the group 1 (nDer p 1, nDer f 1), group 2 (rDer the frame of tropomyosins and mites are shown in Fig. 3. p 2, rDer f 2, rLep d 2) and group 5/21 (rBlo t 5) allergens The sensitization to mite-specific molecules in the con - for mites, and molecule rBla g 1, aspartic protease rBla text of sensitizations to molecules specific for other g 2 and glutathione-S-transferase rBla g 5 for cockroach. inhalant allergens is shown in Fig. 4. Finally, panallergens like mite- and cockroach-derived tropomyosins (rDer p 10 and nBla g 7) were also included Discussion in the analysis and related to sensitizations to other tro- The observed sensitization rate to perennial inhalant- pomyosins (nPen m 1 and rAni s 3). derived molecules in our group of patients is lower than the sensitization rate to pollen-derived components [6]. Results However, the relatively high sensitization rate to mites The results of the analysis describing the HDM and cock - underlines their clinical importance in the Central Euro- roach sensitization patterns in the group of 1255 patients pean region. It needs to be emphasized that in this paper sensitized to at least one allergen component in our we focus only on sensitization rates and not their clinical region are listed below. All percentages were calculated relevance; carrying out the latter analysis without using using the whole group of 1255 patients. specific provocation tests might become rather compli - cated and is not realistic in such large cohorts. Mites The sensitization to at least one mite-specific molecule Cockroach (Der p 1, 2, Der f 1, 2) was observed in 32.7% of patients. It has been suggested that a cocktail of five allergens Bla Isolated sensitizations to molecules derived from glyci- g 1 and/or Per a 1, Bla g 2, Bla g 4, Bla g 5, and Bla g 7 phagid mites Lep d 2 and/or Blo t 5 without sensitization and/or Per a 7 would be expected to diagnose 50–64% to other mite-derived molecules were observed only in of cockroach-allergic patients [15, 16]. The degree of 0.6% of cases. homology between the lipocalin Bla g 4 and the mamma- lian lipocalins is low, and only small cross-reactivity with Cockroach these mammalian allergens would be expected [8]. We True sensitization to at least one cockroach-specific mol - did not analyze this cross-reactivity because of the very ecule (Bla g 1, 2, 5) was very rare (in 0.6% of cases), and low rate of sensitization to Bla g 4 in our patients. The nearly all of them were co-sensitizations with other non- low rate of sensitization to cockroach-derived molecules cockroach-derived molecules, including mite-derived was caused probably rather by the low presence of cock- molecules in half of the patients (4 cases). roaches in our climate than by missing molecules in the used assay. Tropomyosins Sensitization to an inhaled mite- and cockroach-derived Mites tropomyosin was observed in 2.2% of patients (Der p 10 According to several studies, HDM sensitization and in 1.9% and Bla g 7 in 1.5%). allergy are considered to be the most frequent among Co-sensitization of Der p 10 with other mite-derived inhalant allergies [5, 17, 18]. In our conditions, it holds molecules was observed in 0.7% of patients. Co-sensiti- the fourth position behind grass pollen (sensitization fre- zation of Bla g 7 with other cockroach-specific molecules quency for Phl p 1 is 60.8%), birch pollen (sensitization was exceptional (in 0.1%), without co-sensitization to Der frequency for Bet v 1 is 47.3%), and cat allergens (sensi- p 10 in all cases. tization frequency for Fel d 1 is 31.5%) [6], what differs Panzner et al. Clin Transl Allergy (2018) 8:19 Page 4 of 9 25.7% 25.1% 23.5% 23.5% IgE levels 0.3-0.9.ISU 1.0-14.9 ISU 19.0% 18.7% ≥ 15.0 ISU 17.2% 17.1% 10.8% 10.0% 6.1% 5.0% 5.0% 3.6% 3.3% 1.9% 2.7% 1.5% 0.7% 0.5% 0.1% Der p 1Der p 2Der f 1Der f 2Lep d 2Blo t 5Der p 10 Fig. 1 Sensitization rates to mite-derived molecules Fig. 2 Venn diagram depicting mono- and co-sensitizations to mite-derived molecules. Mono- and co-sensitizations with a frequency of less than 0.6% are not shown Panzner et al. Clin Transl Allergy (2018) 8:19 Page 5 of 9 Fig. 3 Venn diagram depicting mono- and co-sensitizations to tropomyosins in relation to sensitization to mites (= sensitization to at least one mite-specific molecule). Mono- and co-sensitizations with a frequency of less than 0.2% are not shown from data coming from other regions [17, 19, 20]. This group 1 allergens in the onset of sensitization, perhaps discrepancy may be caused by geographical differences or mediated by their proteolytic activity and direct epi- may be due to the selected population, mainly consisting thelial damage [27]. The more frequent sensitization to of adults with predominant respiratory allergy. Higher group 2 allergens in the adult population suggested a sensitization rate to grass pollen in adolescents was also later sensitization to group 1 allergens what was docu- shown in a study from northern Italy while the leading mented by observation of a birth cohort [26]. The abil - position of mites was pronounced clearly in smaller chil- ity of group 2 allergens to bind directly to TLR4 might dren [19]. be an explanation for this observation. These facts may It is known that patients sensitized to mites are not also explain that in the case of mites the higher the always sensitized to the molecules used in our study, exposure, the more severe the clinical allergic condi- other molecules may also play a role, but the number tion, in contrast to cat allergens where overexposure of patients sensitized only to these other molecules is seems to lead to tolerance [28]. generally very low [21–25]. Moreover, cysteine pro- Dermatophagoides pteronyssinus is the most wide- tease (Der p 1, Der f 1) signaling has been described spread mite all over the world; it predominates especially to have a strong TH2 up-regulation effect, and group in humid regions where the climate is more influenced 2 allergens have been shown to bind TLR4 via binding by the ocean. Dermatophagoides farinae is supposed LPS, thus having a stronger immunogenic potential fur- to occur more in the continental regions of Europe and ther enhancing the complexity of mite allergy. Hence, the Mediterranean area, but most countries have mixed these molecules may play a leading role in the atopic populations [22, 29]. In our patients, sensitization to D. march, and a differential sensitization rate in children pteronyssinus and D. farinae was almost equal in contrast compared to adults may be present [26]. Sensitization to Spain where the IgE-prevalence to D. pteronyssinus to group 1 allergens was shown to be more frequent allergens was found to be slightly higher than to D. fari- in children [18], thereby suggesting a possible role of nae allergens [18]. Panzner et al. Clin Transl Allergy (2018) 8:19 Page 6 of 9 Fig. 4 Venn diagram depicting mono- and co-sensitizations to different groups of molecules—mites and other inhalant allergens. Sensitization to a group is defined as sensitization to at least one of the respective species-specific component: mites (Der p 1, Der p 2, Der f 1, Der f 2), cat (Fel d 1, Fel d 4), dog (Can f 1, Can f 2, Can f 5), horse (Equ c 1), Alternaria (Alt a 1, Alt a 6), pollens (Phl p 1, Phl p 2, Phl p 4, Phl p 5, Phl p 6, Phl p 11, Cyn d 1, Bet v 1, Aln g 1, Cor a 1, Cup a 1, Cry j 1, Ole e 1, Ole e 9, Pla a 2, Pla l 1, Art v 1, Che a 1). Mono- and co-sensitizations with a frequency of less than 1.0% are not shown Although the pyroglyphid HDM D. pteronyssinus and levels of sensitization to Blo t 5 in our group. The results D. farinae seem to predominate, glyciphagid mites may of another study suggested that allergens different from also be important in some regions [18, 21, 29]. those belonging to group 5 may also be responsible for Blomia tropicalis is the most important house dust the partial cross-reactivity among different mite species mite from the family glycyphagidae. It is most abun- [30]. dant in tropical regions [4, 29]. The major allergen Blo Lepidoglyphus destructor, a glycyphagid storage mite, t 5 shows 40% sequence homology with Der p 5, but it may also become a HDM [29]. Sensitization from domes- was reported not to cross-react with each other [29]. tic exposure was reported from Sweden and France. It is As B. tropicalis does not form part of the acarofauna in not possible to decide whether positivity to Lep d 2 in our Central Europe, the not negligible sensitization rate in patients was due to true sensitization or cross-reactivity our patients seems to be attributable rather to potential within mite group 2 molecules. The absence of mono- cross-reactivity among allergens produced by different sensitizations to Lep d 2 (in the frame of mite-derived mite species (mite group 5/21 molecules) than to true molecules) in our patients testifies rather for Lep d 2 sensitization. This assumption is also supported by low sensitization due to cross-reactivity with other group 2 Panzner et al. Clin Transl Allergy (2018) 8:19 Page 7 of 9 allergens, what is in contradiction to the data suggesting allergens in our patients indicates the greater role of that no such cross-reactivity exists [18]. co-sensitizations. Mite sensitized patients in our group were usually co- sensitized to several mite-specific components; mono - Conclusions sensitization was markedly less frequent (Fig.  2). Der f The vast majority of mite-sensitized patients in our 1 and Der p 1 (cysteine proteases) and Der f 2 and Der group showed polysensitization to two or more com- p 2 (lipid binding proteins) are assumed to be the spe- ponents derived from both major HDM, i.e., D. pteron- cific components most commonly involved in mite yssinus and D. farinae. On the contrary, only a minority allergy. The predominant sensitization, both regard - was sensitized to mite-derived tropomyosin, and these ing prevalence and intensity, to mite group 2 molecules sensitizations were not frequently connected to sensitiza- was already described [17, 18, 25] and confirmed by our tion to other mite-derived molecules, suggesting domi- results. In a French study, predominant sensitization to nating different route of sensitization via food-derived Der p 1 (93%) was detected [31], and we may speculate tropomyosins. that this difference might be due to the different popu - It is necessary to stress the importance of the knowl- lation studied. The same French study also detected a edge of allergen content in mite extracts used for higher frequency of sensitization to Der p 10 (28%) sign- diagnostic and therapeutic purposes as a practical impli- aling the primary sensitizing agent possibly being shrimp cation from this study. Several studies have focused on which is much more consumed in the Mediterranean this issue and analyzed the composition of several com- area than in Central Europe. mercially available preparations concerning their quali- Tropomyosins are molecules responsible for cross- tative and quantitative allergen composition. There are reactivity among mites, shrimp, and cockroach [32]. IgE evident considerable differences in the allergen con - binding to the mite group 10 allergens is rare in Europe tent among the commercially available extracts [9–11]. [21] and Australia [33] and, from one study, in US sub- Although some authors question the necessity of tailor- jects allergic to both HDM and cockroach [34]. Similarly, ing of allergen immunotherapy to the sensitizing species in this study’s population group, sensitization to indi- [22], we consider this to be important for the optimal vidual tropomyosins was considerably less frequent than efficacy of this treatment. Group 2 allergens are highly sensitization to more tropomyosin molecules together cross-reactive, but as group 1 sensitization could be spe- suggesting present cross-reactivity in the frame of this cies specific in some patients and its prevalence is higher group of molecules (Fig. 3). in children, an adequate balance of major mite species Sensitization to the tropomyosin Der p 10 was not and major allergens must be considered in the design of observed frequently (in 1.9%) in our patients, and co- mite allergy vaccines. Regarding the sensitization pat- sensitizations with other mite-specific molecules were terns of patients within the Central European region, not regular (in 0.8%) suggesting the possible different it is necessary to point out the importance of quantify- route of sensitization in a considerable proportion of ing at least three major mite components Der f 1, Der p the patients. Tropomyosins represent clinically relevant 1 and Der f 2 (or Der p 2). Such information is crucial seafood allergens, but the role of mite tropomyosin, Der for effective diagnosis and treatment. Besides these mol - p 10, in house dust mite allergy has not been studied in ecules, Der p 23, a new major house dust mite allergen, detail. A hypothesis that tropomyosin sensitization may should be considered to be an important component for indicate a true food allergy independent of mite respira- allergen-specific immunotherapy as well [26, 36, 37]. The tory disease has been proposed [18]. Another hypothesis importance of eventual further allergens (so-called “mid- pretends that Der p 10 may be a diagnostic marker for tier” allergens—e.g., Der p 5) in this context has yet to be mite-allergic patients with additional sensitization to elucidated. There is an urgent need for rigorous, long- allergens other than Der p 1 and Der p 2. Such patients term clinical trials with an efficacy criterion to find the may require attention when allergen-specific immuno - consensus on the dose of individual molecules in HDM- therapy is considered [35]. allergen-specific immunotherapy [37, 38]. The high rate of simultaneous sensitizations to differ - ent mite components (Fig.  2) may be explained either by co-sensitizations or by cross-reactivities. Specific IgE Abbreviations HDM: house dust mite; IgE: immunoglobulin E; ISAC: immuno solid-phase to Der p 2/Der f 2 is almost fully cross-reactive, but no allergen chip; STROBE: strengthening the reporting of observational studies in cross-reactivity was described with Lep d 2 [18]. Group epidemiology; LPS: lipopolysaccharide. 1 allergens are also cross-reactive, but in some patients, Authors’ contributions a species-specific response was observed [18]. Rela - PP participated in study design, data analysis, and manuscript writing. tively high rate of sensitization both to group 1 and 2 MV participated in study design, data analysis, and manuscript writing. TV Panzner et al. Clin Transl Allergy (2018) 8:19 Page 8 of 9 participated in laboratory analyses, anonymization of the data, and critical 7. Stemeseder T, Klinglmayr E, Moser S, Lueftenegger L, Lang R, Himly M, revision of the manuscript. PV participated in data analysis and critical revision et al. Cross-sectional study on allergic sensitization of Austrian adoles- of the manuscript. PB participated in data analysis and critical revision of the cents using molecule-based IgE profiling. Allergy. 2017;72(5):754–63. manuscript. MM participated in data analysis, statistical calculations, and 8. Pomes A, Arruda LK. Investigating cockroach allergens: aiming to critical revision of the manuscript. All authors read and approved the final improve diagnosis and treatment of cockroach allergic patients. Meth- manuscript. ods. 2014;66(1):75–85. 9. Casset A, Mari A, Purohit A, Resch Y, Weghofer M, Ferrara R, et al. Varying Author details allergen composition and content affects the in vivo allergenic activity of Department of Immunology and Allergology, Faculty of Medicine in Pilsen, commercial Dermatophagoides pteronyssinus extracts. Int Arch Allergy Charles University, Pilsen, Czech Republic. Department of Immunology Immunol. 2012;159(3):253–62. and Allergology, Faculty Hospital in Pilsen, Pilsen, Czech Republic. Depart- 10. Takai T, Okamoto Y, Okubo K, Nagata M, Sakaguchi M, Fukutomi Y, et al. ment of Dermatovenerology, Faculty Hospital in Pilsen, Pilsen, Czech Republic. Japanese Society of Allergology task force report on standardization of The National Institute of Public Health, Prague, Czech Republic. house dust mite allergen vaccines—secondary publication. Allergol Int. 2015;64(2):181–6. Acknowledgements 11. Brunetto B, Tinghino R, Braschi MC, Antonicelli L, Pini C, Iacovacci P. Support to this article has been provided by the EAACI National Society Com- Characterization and comparison of commercially available mite extracts mittee Support Initiative. The authors wish to thank the EAACI NASC for that. for in vivo diagnosis. Allergy. 2010;65(2):184–90. 12. Melioli G, Bonifazi F, Bonini S, Maggi E, Mussap M, Passalacqua G, et al. Competing interests The ImmunoCAP ISAC molecular allergology approach in adult multi- The authors declare that they have no competing interests. sensitized Italian patients with respiratory symptoms. Clin Biochem. 2011;44(12):1005–11. Availability of data and materials 13. Huss-Marp J, Gutermuth J, Schaffner I, Darsow U, Pfab F, Brockow K, et al. Anonymized source data used for the statistical analysis are available at the Comparison of molecular and extract-based allergy diagnostics with Department of Immunology and Allergology of the Faculty of Medicine in multiplex and singleplex analysis. Allergo J Int. 2015;24:46–53. Pilsen. These data are available from the corresponding author on reasonable 14. Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, request. Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med. Consent for publication 2007;4(10):e297. Not applicable. 15. Barbosa MC, Santos AB, Ferriani VP, Pomes A, Chapman MD, Arruda LK. Efficacy of recombinant allergens for diagnosis of cockroach allergy Ethics approval and consent to participate in patients with asthma and/or rhinitis. Int Arch Allergy Immunol. The study was approved by the Ethics Committee of the Faculty Hospital in 2013;161(3):213–9. Pilsen on 6th October 2016 with reference number 404/2016. Data have been 16. Arruda LK, Barbosa MC, Santos AB, Moreno AS, Chapman MD, Pomes A. anonymized before the analysis. Recombinant allergens for diagnosis of cockroach allergy. Curr Allergy Asthma Rep. 2014;14(4):428. Funding 17. Scala E, Alessandri C, Bernardi ML, Ferrara R, Palazzo P, Pomponi D, et al. The study was funded from internal sources of Faculty of Medicine in Pilsen Cross-sectional survey on immunoglobulin E reactivity in 23,077 subjects and Faculty Hospital in Pilsen. No funding was received from any external using an allergenic molecule-based microarray detection system. Clin sources. Exp Allergy. 2010;40(6):911–21. 18. Barber D, Arias J, Boquete M, Cardona V, Carrillo T, Gala G, et al. Analysis of mite allergic patients in a diverse territory by improved diagnostic tools. Publisher’s Note Clin Exp Allergy. 2012;42(7):1129–38. Springer Nature remains neutral with regard to jurisdictional claims in pub- 19. Melioli G, Marcomini L, Agazzi A, Bazurro G, Tosca M, Rossi GA, et al. The lished maps and institutional affiliations. IgE repertoire in children and adolescents resolved at component level: a cross-sectional study. Pediatr Allergy Immunol. 2012;23(5):433–40. Received: 6 December 2017 Accepted: 23 April 2018 20. Westritschnig K, Sibanda E, Thomas W, Auer H, Aspock H, Pittner G, et al. Analysis of the sensitization profile towards allergens in central Africa. Clin Exp Allergy. 2003;33(1):22–7. 21. Pittner G, Vrtala S, Thomas WR, Weghofer M, Kundi M, Horak F, et al. Com- ponent-resolved diagnosis of house-dust mite allergy with purified natu- References ral and recombinant mite allergens. Clin Exp Allergy. 2004;34(4):597–603. 1. Banerjee S, Resch Y, Chen KW, Swoboda I, Focke-Tejkl M, Blatt K, et al. Der 22. Thomas WR. House dust allergy and immunotherapy. Hum Vaccin Immu- p 11 is a major allergen for house dust mite-allergic patients suffering nother. 2012;8(10):1469–78. from atopic dermatitis. J Invest Dermatol. 2015;135(1):102–9. 23. Hales BJ, Elliot CE, Chai LY, Pearce LJ, Tipayanon T, Hazell L, et al. Quantita- 2. Resch Y, Michel S, Kabesch M, Lupinek C, Valenta R, Vrtala S. Different IgE tion of IgE binding to the chitinase and chitinase-like house dust mite recognition of mite allergen components in asthmatic and nonasthmatic allergens Der p 15 and Der p 18 compared to the major and mid-range children. J Allergy Clin Immunol. 2015;136(4):1083–91. allergens. Int Arch Allergy Immunol. 2013;160(3):233–40. 3. Custovic A, Sonntag HJ, Buchan IE, Belgrave D, Simpson A, Prosperi MC. 24. Weghofer M, Grote M, Resch Y, Casset A, Kneidinger M, Kopec J, et al. Evolution pathways of IgE responses to grass and mite allergens through- Identification of Der p 23, a peritrophin-like protein, as a new major Der - out childhood. J Allergy Clin Immunol. 2015;136(6):1645–52. matophagoides pteronyssinus allergen associated with the peritrophic 4. Kidon MI, Chiang WC, Liew WK, Ong TC, Tiong YS, Wong KN, et al. matrix of mite fecal pellets. J Immunol. 2013;190(7):3059–67. Mite component-specific IgE repertoire and phenotypes of allergic 25. Thomas WR. Hierarchy and molecular properties of house dust mite disease in childhood: the tropical perspective. Pediatr Allergy Immunol. allergens. Allergol Int. 2015;64(4):304–11. 2011;22(2):202–10. 26. Posa D, Perna S, Resch Y, Lupinek C, Panetta V, Hofmaier S, et al. Evolution 5. Bousquet PJ, Chinn S, Janson C, Kogevinas M, Burney P, Jarvis D, et al. and predictive value of IgE responses toward a comprehensive panel of Geographical variation in the prevalence of positive skin tests to envi- house dust mite allergens during the first 2 decades of life. J Allergy Clin ronmental aeroallergens in the European Community Respiratory Health Immunol. 2017;139(2):541–9. Survey I. Allergy. 2007;62(3):301–9. 27. Takai T, Ikeda S. Barrier dysfunction caused by environmental proteases in 6. Panzner P, Vachova M, Vitovcova P, Brodska P, Vlas T. A comprehensive the pathogenesis of allergic diseases. Allergol Int. 2011;60(1):25–35. analysis of middle-European molecular sensitization profiles to pollen 28. Renand A, Archila LD, McGinty J, Wambre E, Robinson D, Hales BJ, allergens. Int Arch Allergy Immunol. 2014;164(1):74–82. et al. Chronic cat allergen exposure induces a TH2 cell-dependent Panzner et al. Clin Transl Allergy (2018) 8:19 Page 9 of 9 IgG4 response related to low sensitization. J Allergy Clin Immunol. 34. Satinover SM, Reefer AJ, Pomes A, Chapman MD, Platts-Mills TAE, Wood- 2015;136(6):1627–35. folk JA. Specific IgE and IgG antibody-binding patterns to recombinant 29. Thomas WR. Geography of house dust mite allergens. Asian Pac J Allergy cockroach allergens. J Allergy Clin Immunol. 2005;115(4):803–9. Immunol. 2010;28(4):211–24. 35. Resch Y, Weghofer M, Seiberler S, Horak F, Scheiblhofer S, Linhart B, 30. Simpson A, Green R, Custovic A, Woodcock A, Arruda LK, Chapman MD. et al. Molecular characterization of Der p 10: a diagnostic marker Skin test reactivity to natural and recombinant Blomia and Dermatopha- for broad sensitization in house dust mite allergy. Clin Exp Allergy. goides spp. allergens among mite allergic patients in the UK. Allergy. 2011;41(10):1468–77. 2003;58(1):53–6. 36. Mueller GA, Randall TA, Glesner J, Pedersen LC, Perera L, Edwards LL, et al. 31. Bronnert M, Mancini J, Birnbaum J, Agabriel C, Liabeuf V, Porri F, et al. Serological, genomic and structural analyses of the major mite allergen Component-resolved diagnosis with commercially available D. pteronys- Der p 23. Clin Exp Allergy. 2016;46(2):365–76. sinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite 37. Batard T, Baron-Bodo V, Martelet A, Le Mignon M, Lemoine P, Jain K, et al. allergy. Clin Exp Allergy. 2012;42(9):1406–15. Patterns of IgE sensitization in house dust mite-allergic patients: implica- 32. Ayuso R, Reese G, Leong-Kee S, Plante M, Lehrer SB. Molecular basis of tions for allergen immunotherapy. Allergy. 2016;71(2):220–9. arthropod cross-reactivity: IgE-binding cross-reactive epitopes of shrimp, 38. Calderon M, Casale T, Nelson H, Demoly P. An evidence-based analysis of house dust mite and cockroach tropomyosins. Int Arch Allergy Immunol. house dust mite allergen immunotherapy: a call for more rigorous clinical 2002;129(1):38–48. studies. J Allergy Clin Immunol. 2013;132(6):1322–36. 33. Hales BJ, Martin AC, Pearce LJ, Laing IA, Hayden CM, Goldblatt J, et al. IgE and IgG anti-house dust mite specificities in allergic disease. J Allergy Clin Immunol. 2006;118(2):361–7. Ready to submit your research ? 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Clinical and Translational AllergySpringer Journals

Published: Jun 4, 2018

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