Type-1 Regulatory T-Cell Frequencies Fluctuate in the First 6 months of Peanut Oral Immunotherapy
Monday, March 5, 2018
South Hall A2 (Convention Center)
Sara Anvari, MD, MSc, Levi Watkin, PhD, Sridevi Devaraj, PhD, Victor Cardenas, BSc, Jordan S Orange, MD PhD FAAAAI, Carla M. Davis, MD FAAAAI
RATIONALE: Type-1 regulatory T-cells (Tr1) are antigen induced immunosuppressive T-cells that differ from classic CD4+Foxp3+ Treg cells which are thymic derived. Peanut oral immunotherapy (POIT) has provided desensitization to peanut allergic individuals. Delineation of early immunologic changes contributing to the development of peanut desensitization would help clarify mechanism of action in POIT. Limited immunological evaluation exists during the first 6 months of POIT. Here we analyze peanut specific Treg subpopulations and peanut and Ara h2 IgE in pediatric subjects undergoing POIT in 6 week intervals.

METHODS: In a phase 1 single-center study, 9 subjects between 5-12 years with peanut allergy on POIT underwent immune evaluation at 0, 6, 12, 18 and 24-week time points after initiation of therapy and were compared to 7 healthy controls. The distribution of peanut specific Treg subpopulations and peanut and Ara h2 IgE values were measured in vitro. One-way ANOVA was used for analysis.

RESULTS: Type-1 regulatory (Tr1) T-cell (CD4+CD25+FOXP3-LAG3+CD49b+) frequencies showed a significant fluctuation over the course of evaluation (p=0.012), while Treg (CD4+CD25+FOXP3+CD73+LAP+) frequencies and total Treg populations (CD4+CD25+FOXP3+) showed no significant change (p=0.709 and p=0.315, respectively). The cohort baseline median peanut IgE was 62.5 kU/L (20-329) and Ara h 2 IgE was 70.3 (12-242.5 kU/L). No correlations were observed between Tr1 and IgE values for peanut and Ara h2 when evaluating each time point.

CONCLUSIONS: Decreased peanut specific Tr1 Tregs could be detected as early as 6 weeks on POIT, These findings suggest that Tr1 cells may be an early marker of desensitization in subjects undergoing POIT.