Recombinant T-cell epitope conjugation: A new approach for Dermatophagoides hypoallergen design.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only clinical approach that can potentially cure some allergic diseases by inducing immunological tolerance. Dermatophagoides pteronyssinus is considered as the most important source of mite allergens worldwide, with high sensitization rates for the major allergens Der p 1, Der p 2 and Der p 23. The aim of this work is to generate a hypoallergenic hybrid molecule containing T-cell epitopes from these three major allergens. METHODS: The hybrid protein termed Der p 2231 containing T-cell epitopes was purified by affinity chromatography. The human IgE reactivity was verified by comparing those with the parental allergens. The hybrid was also characterized immunologically through an in vivo mice model. RESULTS: The hybrid rDer p 2231 stimulated in peripheral blood mononuclear cells (PBMCs) isolated from allergic patients with higher levels of IL- 2, IL-10, IL-15 and IFN-γ, as well as lower levels of IL-4, IL-5, IL-13, TNF-α and GM-CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies that blocked the IgE binding to the parental allergens in the serum of allergic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL-10 and IFN-γ and decreased the secretion of IL-4 and IL-5, when compared with parental allergens and D. pteronyssinus extract. CONCLUSIONS: rDer p 2231 has the potential to be used in AIT in patients co-sensitized with D. pteronyssinus major allergens, once it was able to reduce IgE production, inducing allergen-specific blocking antibodies, restoring and balancing Th1/Th2 immune responses, and inducing regulatory T-cells.

Hypertension and Salt-Restrictive Diet Promotes Low Urinary Iodine Concentration in High-Risk Pregnant Women: Results from a Cross-Sectional Study Conducted After Salt Iodination Reduction in Brazil.

During pregnancy, the demand for daily iodine increases by 50-70% which occurs to reach around 250 µg/day. Limited information is available on the association of high-risk pregnancy (HRP) with urinary iodine concentration (UIC) and variables such as socioeconomic factors. To analyze iodine nutritional status and socioeconomic, demographic and anthropometric characteristics among women with HRP screened at the main referral public health center at Bahia, Brazil, a cross-sectional study was conducted in 241 women with HRP (15-46 years old) in Salvador, Bahia, Brazil. The median UIC (MUIC) was 119 µg/L (25-75th, 58.7-200.4 µg/L), indicating mild iodine deficiency. Low UIC (< 150 µg/L) was detected in 61.8% (n = 149) - 18.3% between 100 and 150 µg/L, 24.5% between 50 and 100 µg/L, and 19.1% with UIC < 50 µg/L. Overall, 53% (n = 128) of our population adhered to a low-salt diet, and 32.5% (n = 77) had hypertension. Among the 73% of hypertensive women adhering to a salt-restricted diet, there was a 112% increased risk of iodine deficiency observed (OR = 2.127; 95% confidence interval [1.178-3.829]; p = 0.011). Adhering to a salt-restricted diet was associated with iodine deficiency (OR = 1.82; 95% confidence interval [1.073-3.088], p = 0,026). Hypertension and salt restriction diet significantly increased susceptibility for iodine deficiency in HRP. Therefore, low-salt diet when prescribed to pregnant women (PW) might be carefully followed by iodine nutritional status assessment or universal preconception iodine supplementation.