Th131 - Agnostic Sampling of Singaporean Cohort Reveals Loss of Tolerance in T/B Lymphocytic Axis in House Dust Mite Allergic Individuals

Abstract Text: In Singapore, 70% of the population exhibits positive serological (IgE+) response to House Dust Mites (HDM), why certain individuals who are immunologically sensitized to HDM, can elicit a non-allergic response by maintaining tolerance, remains unknown. This study aims to decipher the T/B lymphocytic immune subsets that contributes to the regulatory axis in HDM allergy with the aid of high parametric CyToF analysis on an agnostic Singaporean cohort. This population was categorised through clinical scoring of plasma IgE reactivity to Derp1 (n=16 IgE-Derp1+, n=16 IgE-Derp1-) and the PBMCs was interrogated with a dedicated T/B cell CyToF panel of 43 markers. Global overview of main immune lineages reveal a distinct gross dysregulation in T and monocytic compartment. Focusing on CD4 Tregs, we discovered there was a distortion in Treg memory and naive ratio, with allergic individuals reflecting a drop in memory Tregs (p < 0.01). In-depth cluster analysis of the Treg compartment, revealed a distinct deficit in the memory CCR4+CCR6+CD154- Treg subset within allergic individuals (p < 0.001), displaying activation marker (HLADR+) and suppressive phenotypes (ICOS+Tigit+). Importantly, they correlate negatively (p < 0.0001) with plasma IgE-Derp1+ levels. Separately within the CD8 compartment, we discovered a similar regulatory deficit in germinal centre targeting CD8+CD45RO+CD27+CXCR5+ (TfH) with TC1 regulatory capacity (TNFa+, IFNg+) in allergic individuals. Overall, we present data on regulatory immune subsets reflecting the loss of tolerance in T/B lymphocytic axis impacting HDM allergic individuals, that could possess therapeutic potential.