[From exposure to control: the application of allergen component-resolved diagnosis in the clinical management of cockroach allergies].

Cockroaches are one of the most common indoor allergens worldwide, and exposure to cockroach allergens (such as the insect body, debris, and secretions) can trigger severe allergic rhinitis and(or) asthma. Currently, the World Health Organization (WHO)/International Union of Immunological Societies (IUIS) has identified 32 allergenic components in cockroaches, but none of these allergens have shown a clear immunodominance. The sensitization rate to cockroach allergens shows significant variability across different regions and populations and exhibits cross-reactivity with various invertebrates, increasing the complexity of clinical diagnosis and treatment. This article delves into the "Molecular Allergology User's Guide 2.0"(MAUG 2.0) published by the European Academy of Allergy and Clinical Immunology (EAACI) and the research progress on cockroach allergies both domestically and internationally. It elucidates the crucial role of allergen component diagnostic technology in enhancing the diagnosis and treatment of cockroach-induced allergic diseases, efficiently assisting clinicians in identifying common sensitizations and cross-reactivities, thereby offering patients more accurate diagnoses and personalized treatment plans.

Production and Release of Proinflammatory Mediators by the Cockroach Allergen Bla g 1 via a Shared Membrane-Destabilization Mechanism.

The cockroach allergen Bla g 1 encloses an exceptionally large hydrophobic cavity, which allows it to bind and deliver unsaturated fatty acid ligands. Bla g 1-mediated delivery of naturally occurring (nMix) ligands has been shown to destabilize lipid membranes, contributing to its digestive/antiviral functions within the source organism. However, the consequences of this activity on Bla g 1 allergenicity following human exposure remain unknown. In this work, we show that Bla g 1-mediated membrane disruption can induce a proinflammatory immune response in mammalian cells via two complementary pathways. At high concentrations, the cytotoxic activity of Bla g 1 induces the release of proinflammatory cytosolic contents including damage-associated molecular patterns (DAMPs) such as heat-shock Protein-70 (HSP70) and the cytokine interleukin-1 (IL-1ß). Sublytic concentrations of Bla g 1 enhanced the ability of phospholipase A2 (PLA2) to extract and hydrolyze phospholipid substrates from cellular membranes, stimulating the production of free polyunsaturated fatty acids (PUFAs) and various downstream inflammatory lipid mediators. Both of these effects are dependent on the presence of Bla g 1's natural fatty-acid (nMix) ligands with CC50 values corresponding to the concentrations required for membrane destabilization reported in previous studies. Taken together, these results suggest that mechanisms through which Bla g 1-mediated lipid delivery and membrane destabilization could directly contribute to cockroach allergic sensitization.

Identification of Per a 13 as a novel allergen in American cockroach.

BACKGROUND: Cockroaches are an important source of indoor allergens. Environmental exposure to cockroach allergens is closely associated with the development of immunoglobulin E (IgE)-mediated allergic diseases. However, the allergenic components in the American cockroaches are not fully studied yet. In order to develop novel diagnostic and therapeutic strategies for cockroach allergy, it is necessary to comprehensively investigate this undescribed allergen in the American cockroach. METHODS: The full-length cDNA of the potential allergen was isolated from the cDNA library of the American cockroach by PCR cloning. Both the recombinant and natural protein molecules were purified and characterized. The allergenicity was further analyzed by enzyme linked immunosorbent assay, immunoblot, and basophil activation test using sera from cockroach allergic patients. RESULTS: A novel allergen belonging to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was firstly identified in the American cockroach and named as Per a 13. The cDNA of this allergen is 1255 base pairs in length and contains an open reading frame of 999 base pairs, encoding 332 amino acids. The purified Per a 13 was fully characterized and assessed to react with IgEs from 49.3 % of cockroach allergic patients, and patients with allergic rhinitis were more sensitized to it. Moreover, the allergenicity was further confirmed by immunoblot and basophil activation test. CONCLUSIONS: We firstly identified GAPDH (Per a 13) in the American cockroach, which is a novel type of inhalant allergen derived from animal species. These findings could be useful in developing novel diagnostic and therapeutic strategies for cockroach allergy.

Prevalence of allergen-specific IgE in southern China: a multicenter research.

Identifying allergen distribution is meaningful and significant for effective diagnosis and treatment of allergic diseases. This study compared the allergen sensitivity in four southern China cities. We enrolled 55,432 participants (27,408 male, 28,024 female) between 2007 and 2019. The allergen-specific IgE levels were compared by the χ2 test. The five prevalent sensitivities were for mite mix (10,985, 19.82%), cockroach (4,860, 8.77%), crab (4,450, 8.03%), fish mix (3,874, 6.99%), and house dust (3,486, 6.29%). Almost all allergen sensitivities decreased with age, particularly from infant to middle aged participants (p < 0.05). An exception was Shenzhen, where food allergen positive rates remained constant in all age groups studied. The proportion of male sensitive to at least one food allergen (OR 1.130; 95% CI 1.088-1.174, p < 0.0025) or aeroallergen (OR, 1.117; 95% CI, 1.078-1.158, p < 0.0025) was higher than female in all four cities. Except for dog dander and tree mix, all aeroallergens differed significantly between seasons (p < 0.05). Liuzhou had the highest rates of food allergen- and aeroallergen-positive participants. The allergen-specific IgE distribution differed among the studied cities, with significant seasonal differences. Young age, male sex, and aeroallergens were risk factors for allergic disease.

Respiratory sensitization to insect allergens: Species, components and clinical symptoms.

Airborne insect particles have been identified as an important cause of respiratory allergies, including allergic asthma and rhinitis. In the literature, the significance of respiratory exposure to insect particles as a cause of occupational allergy has been well-documented. Indeed, many cases of occupational allergy have been reported including allergy to the larvae of flies and moths in anglers and occupationally exposed workers, to grain pests in bakers or other workers handling grains, and to crickets and/or locusts in researchers and workers in aquaculture companies. Furthermore, the prevalence of sensitization to insect allergens is considerably high among patients with asthma and/or rhinitis who are not occupationally exposed to insects, suggesting the clinical relevance of exposure to insects in indoor and outdoor environmental non-occupational settings. Exposure to cockroaches, a well-studied indoor insect, is associated with cockroach sensitization and the development and exacerbation of asthma. Booklice, another common indoor insect, were recently identified as a significant sensitizer of asthmatic patients in Japan and India, and potentially of asthma patients living in warm and humid climates around the world. Lip b 1 was identified as an allergenic protein contributing to the species-specific sensitization to booklice. Moths are considered a significant seasonal outdoor allergen and their allergens are considered to have the highest sensitization rate among Japanese patients. However, other than cockroaches, allergenic insect proteins contributing to sensitization have not been fully characterized to date.

CaMKII oxidation regulates cockroach allergen-induced mitophagy in asthma.

BACKGROUND: Autophagy plays an important role in causing inflammatory responses initiated by environmental pollutants and respiratory tract infection. OBJECTIVE: We sought to investigate the role of cockroach allergen-induced excessive activation of autophagy in allergic airway inflammation and its underlying molecular mechanisms. METHODS: Environmental allergen-induced autophagy was investigated in the primary human bronchial epithelial cells (HBECs) and lung tissues of asthmatic mouse model and patients. The role of autophagy in asthma development was examined by using autophagy inhibitor 3-methyladenine in an asthma mouse model. Furthermore, the involvements of reactive oxygen species (ROS) and oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) signaling in regulating autophagy during asthma were examined in allergen-treated HBECs and mouse model. RESULTS: Cockroach allergen activated autophagy in HBECs and in the lung tissues from asthmatic patients and mice. Autophagy inhibitor 3-methyladenine significantly attenuated airway hyperresponsiveness, TH2-associated lung inflammation, and ROS generation. Mechanistically, we demonstrated a pathological feedforward circuit between cockroach allergen-induced ROS and autophagy that is mediated through CaMKII oxidation. Furthermore, transgenic mice with ROS-resistant CaMKII MM-VVδ showed attenuation of TH2-associated lung inflammation and autophagy. Mitochondrial ox-CaMKII inhibition induced by adenovirus carrying mitochondrial-targeted inhibitor peptide CaMKIIN suppresses cockroach allergen-induced autophagy, mitochondrial dysfunction, mitophagy, and cytokine production in HBECs. Finally, mitochondrial CaMKII inhibition suppressed the expression of one of the key ubiquitin-binding autophagy receptors, optineurin, and its recruitment to fragmented mitochondria. Optineurin knockdown inhibited cockroach allergy-induced mitophagy. CONCLUSIONS: Our data suggest a previously uncovered axis of allergen-ROS-ox-CaMKII-mitophagy in the development of allergic airway inflammation and asthma.

Shrimp and cockroach co-sensitization in Southern China: Association with moth sensitization.

Background: Moth is a common allergen in southern China. Shrimp sensitization might be related to the moth allergen. Objective: This study investigated sensitization to moth allergen in patients in southern China sensitized to shrimp and explored the effect of moth sensitization on different allergic diseases. Methods: Serum samples from 212 patients sensitized to shrimp were tested for specific immunoglobulin E (sIgE) to Dermatophagoides pteronyssinus, crab, cockroach, and moth. Results: The patients sensitized to shrimp were co-sensitized to D. pteronyssinus (88.7%), crab (85.4%), cockroach (89.2%), and moth (92.0%). Overall, 75% of the patients sensitized to shrimp tested positive to the above allergens; only four patients were sensitized to shrimp alone. The median (interquartile range [IQR]) concentrations of sIgE to shrimp (2.66 kU/L [1.02-6.11 kU/L] versus 1.61 kU/L [0.70-3.67 kU/L]), crab (2.35 kU/L [0.83-4.18 kU/L] versus 1.30 kU/L [0.59-3.14 kU/L]), cockroach (3.78 kU/L [0.98-6.91 kU/L] versus 1.56 kU/L [0.85-3.17 kU/L]), and moth (4.70 kU/L [2.98-9.62 kU/L] versus 2.85 kU/L [1.16-7.01 kU/L]) in patients with skin allergic diseases was significantly higher than in patients with respiratory allergic diseases (all p < 0.05). The median (IQR) concentration of sIgE to cockroach in the young adults (2.33 kU/L [0.86-5.56 kU/L]) was the highest among all age groups as well as to moth (young adults: 4.14 kU/L [1.93-8.24 kU/L]). With the increasing positive class of shrimp allergen, the sIgE concentration of moth, cockroach, and crab also increased, and the optimal scaling analysis showed that the sIgE of crab, cockroach, and moth had a strong correlation with sIgE to shrimp (Cronbach α = 93.8%). Conclusion: This study found a high rate of co-sensitization between moth, D. pteronyssinus, cockroach, and crab among patients sensitized to shrimp and a strong correlation between shrimp, moth, and cockroach. Shrimp and cockroach co-sensitization might be related to moth allergens.

A Novel Serine Protease Inhibitor PE-BBI Ameliorates Cockroach Extract-Mediated Airway Epithelial Barrier Dysfunction.

Epithelial barrier dysfunction, characteristic of allergic airway disease may be, at least in part, due to the action of allergen-associated protease activities. Cockroach allergy is a major global health issue, with cockroaches containing considerable serine trypsin-like protease (TLP) activity. The present study sought to evaluate two novel protease inhibitors (PE-BBI and pLR-HL), recently isolated from amphibian skin secretions, for their potential to neutralise cockroach TLP activity and to determine any protective effect on cockroach-induced airway epithelial barrier disruption. Inhibitor potencies against the cockroach-associated activities were determined using a fluorogenic peptide substrate-based activity assay. 16HBE14o- cells (16HBE; a bronchial epithelial cell line) were treated with cockroach extract (CRE) in the presence or absence of the compounds in order to assess cell viability (RealTime Glo luminescent assay) and epithelial barrier disruption (transepithelial resistance and paracellular dextran flux). PE-BBI potently and selectively inhibited CRE TLP activity (pIC50 -8), but not host (16HBE) cell surface activity, which conferred protection of 16HBE cells from CRE-induced cell damage and barrier disruption. Novel protease inhibitor strategies such as PE-BBI may be useful for the treatment of allergic airway disease caused by cockroach proteases.

Effects of educational efforts in tribal homes and schools to reduce asthma triggers, symptoms and missed school days.

Native American asthma prevalence has been estimated higher than for the U.S. population average, and uncontrolled asthma results in absence from schools. This study analyzed effects of targeted education campaigns in both homes and schools on reducing asthma triggers and symptoms among 119 children with asthma, who were recruited from Cherokee and Nez Perce communities. The education campaigns were developed in collaboration with the researchers and the tribes, tailoring strategies to reduce asthma triggers adapted to tribal lifestyles. There was a special emphasis in identification of Traditional Ecological Knowledge (TEK) aspects, which were woven into the study plan and implementation. Some 62 study homes were investigated and the parents received targeted education at the beginning of the study, whereas the remaining control homes received the same education at the end of the study. In Cherokee homes, allergen levels were significantly increased in both control and study groups throughout the study. In Nez Perce homes, dog and cockroach allergen levels decreased significantly in the study homes. The parents reported asthma control test (ACT) scores of the children were significantly improved in both study and control groups, whereas respiratory illness days were reduced in the study group. In schools, allergen levels, particularly cat, dog and cockroach allergens, increased throughout the year in both study and control schools. However, high contact surface cleaning effectiveness based on adenosine tri phosphate (ATP) readings was improved in the study schools. It was also found that high contact surface cleaning effectiveness may have effects on students' absence rates tracked by schools. In conclusion, the results indicate partial improvements in parent reported health symptoms, although the improvements could not be definitively attributed to reduction of any specific exposure in the home environment. In the school environment, effective cleaning throughout the flu season could result in decreased absence rates.