COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors

European Journal of Epidemiology - Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK...     

Apoptotic body-loaded dendritic cells efficiently cross-prime cytotoxic T lymphocytes specific for NA17-A antigen but not for Melan-A/MART-1 antigen

DCs hold promise for cancer immunotherapy due to their functional ambivalence: iDCs internalize antigens, then mDCs trigger naive T-cell activation. However, no consensus has been reached concerning the optimal mode of antigen acquisition for efficient cross-priming of TAA-specific CTLs, and this remains a field of investigation. Here, we used highly purified apobodies derived from an HLA-A*0201-negative melanoma line as a source of tumor antigens for HLA-A*0201 DCs. We compared in vitro mDCs loaded with apobodies to DCs loaded with antigenic peptides, NA17-A(1-9) and Melan-A/MART-1(26-35) A27L analogue, for their capacity to stimulate melanoma antigen-specific T cells from autologous PBLs. Apobody phagocytosis did not induce spontaneous DC maturation, but phagocytic DCs were still responsive to maturation signals, resulting in a functional ability to activate antigen-specific lymphocytes. NA17-A-specific T lymphocytes were activated by both types of stimulation, whereas only peptide-pulsed DCs stimulated the growth of Melan-A/MART-1-specific lymphocytes. We also observed a lack of staining of melanoma-derived apobodies with a Melan-A-specific MAb, suggesting protein alteration during apoptosis induction. After HLA-A*0201/NA17-A multimer sorting, antigen-specific lymphocytes induced by mature DCs loaded with either peptide or apobodies displayed similar functional capacity against peptide-pulsed T2 cells and melanoma cells. Therefore, apobody-loaded DCs can achieve T-cell priming similar to that induced by peptide-pulsed DCs, provided that the apoptotic process allows the preservation of antigen expression.     

Identification of IgE-binding epitopes on gliadins for patients with food allergy to wheat

BACKGROUND: Food allergy to wheat induces different symptoms as atopic eczema/dermatitis syndrome (AEDS), urticaria and more severe reactions as wheat-dependent exercise-induced anaphylaxis (WDEIA). Different gliadin classes are involved in this allergy but IgE-binding epitopes are known only on omega5-gliadins and for WDEIA cases. OBJECTIVES: The aim of the study was to identify IgE-binding epitopes on several gliadin classes and for several patients with different symptoms and ages. METHODS: Eleven sera were analysed by pepscan with overlapping synthetic peptides. RESULTS: Sera from five patients with anaphylaxis, urticaria or WDEIA, displayed strong IgE-binding to sequential epitopes of the repetitive domains of alphabeta, gamma, omega2 or omega5-gliadins with two immunodominant epitopes on omega5-gliadin and a consensus motif of the type QQX1PX2QQ (X1 being L, F, S or I and X2 Q, E or G). One patient allergic to deamidated wheat proteins also had IgE to a repetitive peptide of gamma and omega2-gliadins of the type QPQQPFP. Sera from four patients with AEDS detected no linear epitopes on gliadins, despite the fact that they contained specific IgE to alpha, beta, gamma or omega-gliadins. One child with AEDS recognized cysteine-containing sequences in the nonrepetitive domains of alphabeta and gamma-gliadins. CONCLUSION: B epitopes in wheat allergy were different from B epitopes of coeliac disease. Differences exist in IgE-binding epitopes between patients with food allergy to wheat. IgE from those suffering from WDEIA, anaphylaxis and urticaria detected sequential epitopes in the repetitive domain of gliadins whereas IgE from AEDS patients probably recognized conformational epitopes.     

Disruption of the secretion and action of 17,20β-dihydroxy-4-pregnen-3-one in response to a rise in temperature in the Arctic charr, Salvelinus alpinus. Consequences on oocyte maturation and ovulation

Plasma levels of 17,20β-dihydroxy-4-pregnen-3-one (17,20βP), and the timing of ovulation were investigated in female Arctic charr (Salvelinus alpinus) reared at 5 °C and at 10 °C during the pre-spawning period. The effects of switching from 5 to 10 °C, and from 10 to 5 °C were also investigated. 17,20βP plasma levels were higher at 5 °C than at 10 °C. A switch from 10 to 5 °C stimulated 17,20βP secretion, whereas a switch from 5 to 10 °C had the opposite effect. Ovulation occurred spontaneously in the females kept at 5 °C, and in those switched from 10 to 5 °C. In contrast, ovulation was inhibited in females reared at 10 °C, and in those switched from 5 to 10 °C. Oocyte maturation at 5 °C and at 10 °C in the presence of LH or of 17,20βP was also investigated in vitro using donor females reared at 5 or 10 °C. Both LH and 17,20βP stimulated oocyte maturation more effectively in oocytes incubated at 5 °C than at 10 °C. At both incubation temperatures, the rearing temperature of the donor females had a significant impact on their responsiveness to LH stimulation, but had no effect on their responsiveness to 17,20βP stimulation. In addition to the inhibition of LH secretion, which had already been reported, the results reported here show that in Arctic charr raising the temperature above the physiological range reduces both follicular responsiveness to LH stimulation and the sensitivity of oocytes to 17,20βP stimulation.     

Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking

European Journal of Epidemiology - Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought...     

Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions

Probiotics and prebiotics, alone or together (synbiotics), can influence the intestinal microbiota and modulate the immune response. They may therefore be tools that can prevent or alleviate certain pathologies involving the gut immune system, such as allergies for which no treatment is yet available. This review focuses first on the definitions of probiotics, prebiotics, and synbiotics and key cells in the gut immune system. It then discusses their effects on mucosal immune stimulation. Experimental findings suggest that different probiotic species have similar effects on innate immunity by improving the mechanisms of pathogen destruction. On the contrary, their impacts seem to be variable on the adaptive immune system. Prebiotics can also exert an influence on the gut immune system via the stimulation of the autochthonous bacteria metabolism. Finally, this review focuses on the effects of food supplements on allergy. Different studies performed in humans or rodents have supported a potential role for selected probiotics and prebiotics in reducing some allergic parameters. Probiotic effects on allergy treatment are unclear, especially in human studies. However, they are potentially effective at short-term for prevention when they are administered in perinatal conditions. A clinical study performed with an infant cohort revealed a beneficial effect of prebiotics in preventing allergic manifestations at long-term. Further studies are nonetheless essential to confirm these findings. Food supplements offer potential tools for the prevention or treatment of allergy, but insufficient evidence is available at present to recommend their use in clinical practice.     

Genomic and physiological footprint of the Deepwater Horizon oil spill on resident marsh fishes

The biological consequences of the Deepwater Horizon oil spill are unknown, especially for resident organisms. Here, we report results from a field study tracking the effects of contaminating oil across space and time in resident killifish during the first 4 mo of the spill event. Remote sensing and analytical chemistry identified exposures, which were linked to effects in fish characterized by genome expression and associated gill immunohistochemistry, despite very low concentrations of hydrocarbons remaining in water and tissues. Divergence in genome expression coincides with contaminating oil and is consistent with genome responses that are predictive of exposure to hydrocarbon-like chemicals and indicative of physiological and reproductive impairment. Oil-contaminated waters are also associated with aberrant protein expression in gill tissues of larval and adult fish. These data suggest that heavily weathered crude oil from the spill imparts significant biological impacts in sensitive Louisiana marshes, some of which remain for over 2 mo following initial exposures.     

Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?

Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory-to-laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians.