Cockroach allergen exposure and plasma cytokines among children in a tropical environment

Medsker, Brock H.; Forno, Erick; Han, Yueh‐Ying; Acosta‐Pérez, Edna; Colón-Semidey, Angel; Alvarez, María; Alcorn, John F.; Canino, Glorisa; Celedón, Juan C.

doi:10.1016/j.anai.2017.05.008

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…Cockroach sensitization and exposure have been established as a leading risk factor for morbidity in children with asthma living in low‐income, US urban communities, and many other parts of the world 3‐8 . Environmental approaches, eradication and avoidance, have been the focus for ameliorating the effects of cockroach exposure.…”

Section: Introductionmentioning

confidence: 99%

Development of nasal allergen challenge with cockroach in children with asthma

Spergel

Sever

Johnson

et al. 2021

Pediatric Allergy Immunology

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Background Nasal allergen challenge (NAC) could be a means to assess indication and/or an outcome of allergen‐specific therapies, particularly for perennial allergens. NACs are not commonly conducted in children with asthma, and cockroach NACs are not well established. This study's objective was to identify a range of German cockroach extract doses that induce nasal symptoms and to assess the safety of cockroach NAC in children with asthma. Methods Ten adults (18‐37 years) followed by 25 children (8‐14 years) with well‐controlled, persistent asthma and cockroach sensitization underwent NAC with diluent followed by up to 8 escalating doses of cockroach extract (0.00381‐11.9 µg/mL Bla g 1). NAC outcome was determined by Total Nasal Symptom Score (TNSS) and/or sneeze score. Cockroach allergen–induced T‐cell activation and IL‐5 production were measured in peripheral blood mononuclear cells. Results 67% (6/9) of adults and 68% (17/25) of children had a positive NAC at a median response dose of 0.120 µg/mL [IQR 0.0380‐0.379 µg/mL] of Bla g 1. Additionally, three children responded to diluent alone and did not receive any cockroach extract. Overall, 32% (11/34) were positive with sneezes alone, 15% (5/34) with TNSS alone, and 21% (7/34) with both criteria. At baseline, NAC responders had higher cockroach‐specific IgE (P = .03), lower cockroach‐specific IgG/IgE ratios (children, P = .002), and increased cockroach‐specific IL‐5–producing T lymphocytes (P = .045). The NAC was well tolerated. Conclusion We report the methodology of NAC development for children with persistent asthma and cockroach sensitization. This NAC could be considered a tool to confirm clinically relevant sensitization and to assess responses in therapeutic studies.

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Section: Introductionmentioning

confidence: 99%

Development of nasal allergen challenge with cockroach in children with asthma

Spergel

Sever

Johnson

et al. 2021

Pediatric Allergy Immunology

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“…These allergens are often composed of various components, such as enzymes and complex polysaccharides. Certain enzymatically active components derived from allergens, including Der p and Der f from HDMs 4,5 , Asp f from Aspergillus oryzae 6 , the Subtilisin protease from Bacillus species 7 and Per a from cockroaches 8,9 , have been reported to have the ability to induce IL-33 release and promote allergic-type 2 airway in ammation in vivo. Allergen proteases induce an allergic in ammatory response through mechanisms that involve directly damaging epithelial cell tight junctions 10,11,12,13 , acting on protease-activated receptors (Par2) or activating the pattern recognition receptor Toll-like receptor 4 (TLR4) on multiple cell lineages, including airway epithelial cells, macrophages and basophils 10,14,15 .…”

Section: Introductionmentioning

confidence: 99%

Allergen protease-induced Gsdmd p40 controls IL-33 secretion

Sun

et al. 2021

Preprint

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Interleukin (IL)-33, an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammation, such as that in asthma. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we demonstrated that Gasdermin D (Gsdmd) functions as a conduit for IL-33 secretion following allergen protease exposure. Gsdmd was rapidly cleaved into a functional neo-form, the N-terminal p40 fragment (p40 NT-Gsdmd), in the murine airway epithelium when cells were exposed to allergen proteases from fungi, house dust mites (HDMs), or bacteria. This cleavage event that produces the p40 Gsdmd fragment was independent of inflammatory caspases-1/11, as it could not be inhibited by caspase-1 and caspase-11 deficiency in murine cells. The functional p40 NT-Gsdmd fragment directly contributed to the secretion of both the nuclear full-length form and cytosolic mature form of IL-33. Both Gsdmd deficiency and blockade of the generation of p40 by amino acid mutation or deletion of residues 308–313 (ELRQQ) in the Gsdmd sequence could efficiently prevent IL-33 release in airway epithelial cells. In mice, Gsdmd deficiency prevented IL-33 release and hindered the activation of group 2 innate lymphoid cells (ILC2s), thus alleviating airway inflammation and lung tissue damage after stimulation with HDMs or papain. Our findings uncovered a mechanism of Gsdmd-mediated IL-33 release under allergen exposure and offer insight into Gsdmd cleavage prevention as a potential approach to reduce allergic airway inflammation.

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