FOXP3 and TGF-β: Differential Regulatory Molecules between Sensitization and Tolerance to Olive Pollen

Different molecular mechanisms may modulate sensitization and natural or induced tolerance to allergens. We have searched for differential mechanisms at humoral and cellular level in the olive pollen allergic response, checking the influence of exposure to allergens of subjects from an area with extremely high antigenic load during the pollen season. Sera and PBMCs were obtained during and outside the pollen season. Distinct Ig subtypes (total IgE and specific IgE, IgG4 and IgA), and Th1, Th2 and regulatory T cells (Treg) cytokines were analyzed in 5 groups of subjects: Group 1, non-allergic; Group 2, asymptomatic, sensitized to olive pollen; Group 3, allergic to pollen other than olive; Group 4, allergic to olive pollen (not treated); and Group 5, allergic to olive pollen, and getting specific immunotherapy. Asymptomatic subjects showed the highest total IgE levels. The major difference found between untreated and treated subjects was the high levels of non-inflammatory antibodies (IgG4) in treated Patients. The main result of cytokine analyses was the statistically significant decrease in TGF-β levels in untreated olive pollen allergic subjects (pollen season) compared with treated. A significant decrease in forkhead winged-helix transcription factor (FOXP3) mRNA expression (marker of regulatory response) and a lower presence of Treg cells in PBMCs of olive pollen allergic subjects was found. The results Point to a decrease in the cellular regulatory mechanisms mediated by TGF-β and FOXP3 in olive-pollen allergic patients that could be restored after specific-immunotherapy

Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Sociedad Española de Trasplante.Introduction: Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients. Methods: We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. Results: Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug. Conclusion: In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy

Plant size, latitude, and phylogeny explain within-population variability in herbivory

Interactions between plants and herbivores are central in most ecosystems, but their strength is highly variable. The amount of variability within a system is thought to influence most aspects of plant-herbivore biology, from ecological stability to plant defense evolution. Our understanding of what influences variability, however, is limited by sparse data. We collected standardized surveys of herbivory for 503 plant species at 790 sites across 116° of latitude. With these data, we show that within-population variability in herbivory increases with latitude, decreases with plant size, and is phylogenetically structured. Differences in the magnitude of variability are thus central to how plant-herbivore biology varies across macroscale gradients. We argue that increased focus on interaction variability will advance understanding of patterns of life on Earth