Component-Resolved Diagnosis of American Cockroach (Periplaneta americana) Allergy in Patients From Different Geographical Areas

Abstract

Background: Manifestation of respiratory allergy to American cockroach (Periplaneta americana) is prominent in the subtropical and tropical areas. However, co-existing perennial indoor inhalant allergies frequently compromise clinical diagnosis of cockroach allergy, and the analysis of sensitization pattern is limited by the lack of Periplaneta allergens widely available for component-resolved diagnostics (CRD).Objective: To evaluate a collection of previously described recombinant Periplaneta allergens for CRD in cockroach allergy.Methods: A panel of nine recombinant Periplaneta allergens (Per a 1–5, 7–10) was generated, purified, and subjected to physicochemical characterization by applying circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), amino acid (AA) analysis, and mass spectrometry (MS). Patients (n = 117) from India, Korea, Venezuela, and Iran, reporting perennial respiratory indoor allergies with IgE sensitization to cockroach (P. americana and/or Blattella germanica), were included. The sensitization profile was monitored by the experimental ImmunoCAP testing.Results: ImmunoCAP testing confirmed IgE sensitization to Periplaneta and/or Blattella extract in 98 of 117 patients (r = 0.95). Five out of 117 patients were sensitized to only one of the two cockroach species. Within the whole study group, the prevalence of sensitization to individual allergens varied from 4% (Per a 2) to 50% (Per a 9), with the highest IgE values to Per a 9. Patients from four countries displayed different sensitization profiles at which Per a 3 and Per a 9 were identified as major allergens in India and Korea. Periplaneta-derived lipocalin and myosin light chain were characterized as new minor allergens, designated as Per a 4 and Per a 8. Periplaneta extract showed higher diagnostic sensitivity than all individual components combined, suggesting the existence of allergens yet to be discovered.Conclusion: Utilization of a panel of purified Periplaneta allergens revealed highly heterogeneous sensitization patterns and allowed the classification of lipocalin and myosin light chain from Periplaneta as new minor allergens.

Genome assembly and annotation of Periplaneta americana reveal a comprehensive cockroach allergen profile

“…According to in silico prediction, multiple P. americana potential allergens, such as enolase, cofilin, alpha‐tubulin, paramyosin, and troponin C, have never been categorized as Per a allergens previously (Table S10). This has confirmed Wangorsch's hypothesis that many novel allergen groups have not yet been discovered in P. americana owing to limitations in cost and throughput using conventional approaches 32 . Enolase has been used to demonstrate how a novel allergen group can be disclosed by integrating proteomic analysis and bioinformatics tools.…”

“…However, we are facing great challenges in achieving diagnostic sensitivity as displayed by the natural cockroach extract owing to the incomplete allergen profile available, the lack of immunodominant allergens, the variability of allergen content in cockroach extracts, and the heterogeneous pattern of IgE sensitivity among different patient collectives (Table S14). 32,65–69 The incorporation of the old collective with our newly identified allergens, especially those belonging to novel groups, could potentially result in diagnostic tests with stronger IgE sensitivity and thus improve the efficacy and accuracy of species‐specific component‐resolved diagnosis in certain populations. In addition, the lack of a standardized cockroach extract has also made it difficult to implement cockroach immunotherapy as a routine process in clinics, although more and more trials suggested it to be a promising treatment strategy for cockroach allergy 70 .…”

“…63 Despite that, the highly diversi- S14). 32,[65][66][67][68][69] The incorporation of the old collective with our newly identified allergens, especially those belonging to novel groups, could potentially result in diagnostic tests with stronger IgE sensitivity and thus improve the efficacy and accuracy of species-specific component-resolved diagnosis in certain populations. In addition, the lack of a standardized cockroach extract has also made it difficult to implement cockroach immunotherapy as a routine process in clinics, although more and more trials suggested it to be a promising treatment strategy for cockroach allergy.…”

“…Like most allergies, the current diagnosis of cockroach allergy is mainly based on the results of the SPT or the measurement of specific IgE sensitivity to cockroach allergens. A panel of purified recombinant cockroach allergens has been previously established in facilitating the component‐resolved diagnosis, in which the IgE specificity of each component and the sensitization profile of the patients have been resolved 32,65 . However, we are facing great challenges in achieving diagnostic sensitivity as displayed by the natural cockroach extract owing to the incomplete allergen profile available, the lack of immunodominant allergens, the variability of allergen content in cockroach extracts, and the heterogeneous pattern of IgE sensitivity among different patient collectives (Table S14).…”

“…in P. americana owing to limitations in cost and throughput using conventional approaches. 32 Enolase has been used to demonstrate how a novel allergen group can be disclosed by integrating proteomic analysis and bioinformatics tools. Enolase was reported to be a Bla g allergen in 2010 33 ; however, it has not been recorded in the WHO/IUIS Allergen Nomenclature database owing to the lack of convincing evidence of allergenicity as well as protein and gene sequences.…”