The association of allergic sensitization patterns in early childhood with disease manifestations and immunological reactivity at 10 years of age

Abstract

Background: Allergy to German cockroach (CR) is common in urban environmentsand is an important allergen in children with asthma.Objective: We hypothesize that the evolution of allergic sensitization and clinical disease is associated with distinct patterns of allergen-specific T cell reactivity. To test this hypothesis, a subset of high-risk inner-city children participating in the URECA (Urban Environment and Childhood Asthma) birth cohort were selected to evaluate CR-specific T cell reactivity from three distinct groups based on acquisition of aeroallergen sensitivity from ages 2 to 10: low atopy with minimal to no sensitivity (n = 26), early-onset allergic sensitization (n = 25) and late-onset allergic sensitization (n = 25).Methods: Using pools of previously identified CR-derived T cell epitopes, we characterized the allergen-specific T cell response in these 76 subjects from blood samples obtained at age 10. CR-specific production of IL-5, IFNγ and IL-10 was measured by ELISPOT following two-week in vitro culture with CR extract.Results: T cell responses were significantly higher in the early-onset atopy group compared to low atopy (P = 0.01), and a trend for higher cytokine production in the late onset compared to the low atopy cohort was also observed (P = 0.06). T cell responses were similar between early-and late-onset cohorts. Furthermore, a comparison of T cell reactivity between asthmatic and non-asthmatic individuals revealed significantly higher cytokine production in asthmatics compared to non-asthmatics (P = 0.02) within both the CR-allergic and non-allergic cohorts. Conclusions and clinical relevance:In conclusion, the present study reports that higher T cell reactivity is associated with allergen sensitization and asthma.Interestingly, no significant difference in T cell reactivity was observed in allergic children with early-onset versus late-onset atopy. K E Y W O R D Sallergens and epitopes, asthma, IgE, T cells

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.…”

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

“…CR-specific T cell responses have been characterized in relatively low detail ( 5 – 7 , 47 ), and very little information is available particularly addressing if T cells play a role in cockroach allergic sensitization. Although it has been shown that higher T cell reactivity is associated with allergen sensitization and asthma ( 48 ), future studies are warranted to elucidate to which extent T cell responses correlate with clinical symptoms or disease severity. An important implication of the current study is that knowledge of individual reactivity profiles will help to interpret outcomes of cockroach immunotherapy, according to the allergens present in the cockroach extract used for treatment.…”

T cell responses, diagnosing peanut allergy and group clinic consultations

“…In this issue of the Journal, Schulten et al assess whether the development of allergic sensitization and clinical disease is associated with specific patterns of allergen‐specific T cell reactivity towards German cockroach. They used a subgroup from the URECA (Urban Environment and Childhood Asthma) high‐risk birth cohort.…”