Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired.

BACKGROUND: Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (TR1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen-specific TR1 cell induction has not been established. OBJECTIVES: We sought to determine whether peanut-specific TR1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut-specific TR1 cells induced from healthy control (HC) subjects. METHODS: Tolerogenic dendritic cells were differentiated in the presence of IL-10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen-presenting cells for autologous CD4+ T cells (CD4+ T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea-T10 cells]). Pea-T10 cells were characterized by the presence of CD49b+ lymphocyte-activation gene 3 (LAG3)+ TR1 cells, antigen-specific proliferative responses, and cytokine production. RESULTS: CD49b+LAG3+ TR1 cells were induced in pea-T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea-T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high TH2 cytokine production upon peanut-specific restimulation. CONCLUSIONS: Peanut-specific TR1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable TR1/TH2 ratio is discussed as a possible cause of PA TR1 cell impairment.

Predicted Effects and Cost-Effectiveness of Wheat Flour Fortification for Reducing Micronutrient Deficiencies, Maternal Anemia, and Neural Tube Defects in Yaoundé and Douala, Cameroon.

BACKGROUND: Policy makers aiming to reduce micronutrient deficiencies (MNDs) and their health effects must choose among alternative definitions of impact when evaluating cost-effectiveness. OBJECTIVE: Estimate the cost-effectiveness of a mandatory wheat flour fortification program for reducing cases of MNDs (iron, zinc, folate, vitamin B12), anemia and neural tube defects (NTDs) averted, and disability-adjusted life years (DALYs) averted in urban Cameroon. METHODS: A 13-year predictive model was developed, including a 3-year start-up period and 10 years of program activity. Costs were estimated using historical program budgets. Effects were calculated based on observed changes in prevalence of MND and anemia 1 year postfortification and predicted reductions in NTDs based on NTD burden and wheat flour intake. Total DALYs averted were estimated for anemia and NTDs. RESULTS: The program cost ∼$2.4 million over 13 years and averted an estimated ∼95 000 cases of maternal anemia and ∼83 500 cases of iron deficiency among children after 1 year. Cost/case-year averted for MNDs ranged from $0.50 for low plasma folate to $3.30 for iron deficiency and was $2.20 for maternal anemia. The program was predicted to avert 1600 cases of NTDs over 10 years at ∼$1500 per case averted. Estimated cost/DALY averted was $50 for NTDs and $115 for anemia. CONCLUSIONS: In Cameroon, cost-effectiveness of wheat flour fortification varied by the measure of impact employed, but was classified as "very cost-effective" for all outcomes using World Health Organization criteria. Policy makers and their advisors must determine how best to use information on program costs and benefits to inform their decisions.