IgE and T Cell Reactivity to a Comprehensive Panel of Cockroach Allergens in Relation to Disease

Abstract

IgE sensitization to cockroach allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach allergens we previously reported for the same cohort. Ex vivo T cell activation (Ox40/PDL-1 expression) of PBMCs stimulated with peptide pools derived from 11 German cockroach proteins, including nine official cockroach allergens, plus chitinase and vitellogenin, was determined by flow cytometry. IgE prevalences to chitinase (17%) and hemocyanin (44%) were comparable to values for the other eight allergens that we previously reported (21–57%). Hemocyanin (Bla g 3), was a major allergen (one to which more than 50% of patients with an allergy to its source react) for a sub-group of 15 highly cockroach-sensitized subjects (IgE > 3.5 kUA/L: 53%). Chitinase was officially named as new allergen Bla g 12. Cockroach-specific IgE levels in plasma showed excellent correlation with the sum of 10 allergen-specific IgE (r = 0.94, p < 0.001). T cell reactivity to 11 proteins was highly variable among subjects, the highest being for vitellogenin, followed by Bla g 3. The main finding was that cockroach allergen-specific IgE and T cell reactivity patterns were unique per subject, and lacked immunodominant allergens and correlation with clinical phenotype/disease severity in the studied cohort. Knowing the subject-specific B/T cell reactivity profiles to a comprehensive panel of cockroach allergens will contribute to diagnosis of cockroach allergy and will be important for planning and assessing allergen immunotherapy outcomes, according to the allergen content in therapeutic cockroach extracts.

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen‐specific T cell responses in allergic sensitized children

“…In This study is to the best of our knowledge, the first characterization of ex vivo CR-specific CD4+ T cell responses in CR-sensitized urban and under-resourced children with asthma, and for the majority of the known CR allergens to date, which are also components commonly found in CR extracts used for IT. 2,10 Our results also differ from previous attempts of portrayal of CR-specific responses, 17,19,20 because of the high level of granularity and because the ex vivo sponses, namely to cat dander, fungus, mite and grass or birch pollen 30,46,47 using ex vivo methodologies similar to our study. It is possible that the ex vivo assay strategy utilized contributed to reveal this heterogeneity, as previous allergy studies in the case of CR 16,18,20 or other allergens 24,27 utilized in vitro restimulation protocols which might obscure and blunt differences.…”

“…This study is to the best of our knowledge, the first characterization of ex vivo CR‐specific CD4+ T cell responses in CR‐sensitized urban and under‐resourced children with asthma, and for the majority of the known CR allergens to date, which are also components commonly found in CR extracts used for IT. 2 , 10 Our results also differ from previous attempts of portrayal of CR‐specific responses, 17 , 19 , 20 because of the high level of granularity and because the ex vivo approach allowed to characterize responding cells to a minimal gap from bona fide in vivo responses.…”

“…[4][5][6][7][8] Several studies defined CR allergens based on IgE reactivity from sensitized individuals and correlated sensitization prevalence with severity of clinical symptoms. 3,[9][10][11][12] T cells, and in particular type 2T helper cells, significantly contribute to the development of allergy and asthma [13][14][15] ; however, CR-specific T cell responses have been characterized in less detail, [16][17][18][19][20][21] and very little information is available particularly for the population most impacted by CR allergies, namely urban and under-resourced children.…”

Investigation of <i>Blattella germanica</i> Sensitivity in Atopic Children

“…Çocukluk çağı astımının ve alerjik solunum yolu hastalıklarının patogenezinde hamam böceği alerjisinin önemli bir yeri vardır (1). Hamam böceği alerjenleri, özellikle astım ve alerjik rinitte semptomlardan sorumlu alerjenler arasında yer alır (2)(3)(4). Hamam böceği duyarlılık sıklıkları çevresel koşullarla ilişkili olarak bölge ve ülkelere göre oldukça değişkenlik göstermektedir.…”

“…En sık görülen ev içi hamam böceği türleri Alman (Blattella germanica) ve Amerikan (Periplaneta americana) hamam böcekleridir ve sırasıyla ılıman ve tropikal bölgelerde yaygın olarak bulunmaktadırlar (12). Dünyanın ılıman bölgelerinde ve Avrupa ülkelerinde alerji ile en sık ilişkilendirilen türdür (2,3). Türkiye'de de ılıman iklim nedeniyle en sık karşılaşılan hamam böceği tipi Blattella germanica'dır (8,9).…”