Associations of Th2, Th17, Treg cells, and IgA⁺ memory B cells with atopic disease in children: The Generation R Study

Abstract

Background: New insights into immune cells could contribute to treatment and monitoring of atopic disease. Because nongenetic factors shape the human immune system, we here studied these immune cells in a large cohort with atopic children with adjustment for prenatal and postnatal confounders. Methods: Information on atopic dermatitis, inhalant-and food-allergic sensitization, asthma lung function scores was obtained from 855 10-year-old children within the Generation R cohort. 11-color flow cytometry was performed to determine CD27 + and CD27 − IgG + , IgE + and IgA + memory B cells, Th1, Th2, Th17, and Treg-memory cells from venous blood. Associations between any atopic disease, the individual atopic diseases, and immune cell numbers were determined. Results: Children with any atopic disease had higher Th2, Treg, Treg-memory, and CD27 + IgA + memory B-cell numbers compared to children without atopic disease. When studying the individual diseases compared to children without the individual diseases, children with atopic dermatitis, inhalant-, and food-allergic sensitization had higher memory Treg cell numbers 12.3% (95% CI 4.2; 21.0), (11.1% (95% CI 3.0; 19.8), (23.7% (95% CI 7.9; 41.8), respectively. Children with food-allergic sensitization had higher total B and CD27 + IgA + memory B-cell numbers (15.2% [95% CI 3.2; 28.7], 22.5% [95% CI 3.9; 44.3], respectively). No associations were observed between asthma and B-or T-cell numbers. | 179 LOOMAN et AL.

Recent developments and highlights in immune monitoring of allergen immunotherapy

“…Many abnormalities in Treg and Th cell number and frequency have been observed within the total pool of circulating T cells, independent of antigen specificity . With the use of MHC‐peptide reagents to detect antigen specificity, the sensitivity of these changes can be significantly enhanced to detect early effects of AIT .…”

“…Long-lived memory Th2 and memory B cells specific for the allergen remain, 30,31 and these will trigger a hypersensitivity response when the individual is challenged by renewed encounter with the same allergen.…”

“…The latter can also be examined in the context of single cells through advances in multi-parameter flow cytometry and mass cytometry. 31,61,62 Finally, metabolomic and lipidomic approaches have been developed to evaluate chemical processes in the body through analysis of endogenous (amino acids, fatty acids, vitamins) or exogenous (toxins, drugs) molecules in serum and faecal samples. 63,64 Advances in Omic technologies are driving the field with the accumulation of large data sets for interrogation and opportunities to identify immune biomarkers for patient stratification, prognostication and therapy monitoring.…”

“…32,33,114,115 To facilitate translation towards routine measurements of T-cell biomarkers, immunophenotyping approaches have been developed that only use membrane markers and allow for direct ex vivo T-cell evaluation without in vitro cell culture. The CD4+CD25+CD127phenotype specifically distinguishes human Treg, 116,117 and these cells can be quantified in allergic patients 31 with increases following SLIT for grass pollen 11 and AIT in HDM-allergic individuals. 32 Furthermore, chemokine receptor expression patterns correlate strongly with Th cell function [118][119][120] and can be used to identify Th1 (CCR6-CXCR3+CCR4-), Th2 (CCR6-CXCR3-CCR4+) and Th17…”

“…42,123 Many abnormalities in Treg and Th cell number and frequency have been observed within the total pool of circulating T cells, independent of antigen specificity. 30,31,42,121 With the use of MHC-peptide reagents to detect antigen specificity, 115 the sensitivity of these changes can be significantly enhanced to detect early effects of AIT. 32,113 As the application of MHC tetramers, especially for MHC class II, is limited by the diversity of alleles in the human population, there is a need for alternative markers for allergen-specific cells.…”