Background
Compositional changes in the early‐life gut microbiota have been implicated in IgE‐associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota ...development from infancy to school age in relation to onset of IgE‐associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T‐cell regulation, estimated as responses to polyclonal T‐cell activation.
Methods
Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL‐10 and FOXP3 mRNA copies were determined using real‐time quantitative reverse transcriptase‐PCR.
Results
At 8 years of age, 21 children were diagnosed with IgE‐associated allergic disease and 90% displayed allergic comorbidity. Seventy‐two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8‐year‐olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus, and Lachnospira. In allergic 8‐year‐olds, Faecalibacterium correlated with IL‐10 mRNA levels (rs = 0.49, Padj = 0.02) with the same trend for FOXP3 (rs = 0.39, Padj = 0.08).
Conclusions
We identified both temporal and long‐term variation in the differential abundance of specific bacterial genera in children developing IgE‐associated allergic disease. Improved dietary interventions aiming at expanding immune‐modulatory taxa could be studied for prevention of allergic disease.
Gut microbiota development was studied prospectively from infancy to school age in relation to onset of IgE‐associated allergic diseases. We also examined correlations between gut microbiota and T‐cell regulatory markers. We identified temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. In allergic 8‐year‐olds, Faecalibacterium correlated with polyclonally activated IL‐10 mRNA levels of peripheral blood mononuclear cells, with the same trend for FOXP3.
Background
Long‐term effects of probiotics in primary prevention of allergic disease need further evaluation. We previously reported a reduced cumulative incidence of infant eczema by feeding ...Lactobacillus paracasei ssp paracasei F19 (LF19) during weaning. Therefore, we assessed effects of LF19 on the prevalence of allergic disease at school age.
Methods
In a double‐blind placebo‐controlled trial infants were randomized to daily intake of cereals with (n = 89) or without LF19 108 CFU (n = 90) from 4–13 months of age. At age 8–9, we evaluated the prevalence of allergic disease (eczema, allergic rhinitis, asthma, and food allergy) by clinical examination and validated questionnaires. IgE sensitization was assessed by skin prick test (inhalant allergens) and specific IgE levels (food allergens). Lung function was evaluated by a spirometry reversibility test. Fractional exhaled nitric oxide (FENO) was measured.
Results
Of 171 children that completed the intervention, 121 were assessed at age 8–9. In the probiotic group, 15/59 (25%) were diagnosed with any allergic disease vs 22/62 (35%) in the placebo group OR (95% CI) 0.62 (0.28–1.36). Corresponding numbers for IgE‐associated allergic disease were 9/53 (17%) vs 12/59 (20%) 0.80 (0.31–2.09). Median (25th‐75th percentile) FENO was 9 (8–12) in the probiotic vs 8 (7–12) ppb in the placebo group (P > 0.05). There was no effect of LF19 on lung function measures (P > 0.05).
Conclusions
There was no long‐term effect of LF19 on any diagnosed allergic disease, airway inflammation or IgE sensitization. This suggests delayed eczema onset but to fully examine long‐term benefits a larger study population had been needed.
Objectives
To determine the prevalence of myasthenia gravis (MG) and the rate of concurrent autoimmune diseases in patients with MG.
Design and setting
Using the Swedish health and population ...registers, during the period 2005–2010, we conducted a nested case–control study of patients with MG (n = 2045) with five age‐ and sex‐matched population‐based controls per case. Register‐based MG diagnosis was validated against the Stockholm MG Cohort. Similar nested case–control studies were conducted in patients with multiple sclerosis (MS), as a neuroinflammatory disease control, and siblings of patients with MG.
Main outcome measure
Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated as a measure of the association between MG and other autoimmune diseases.
Results
The prevalence of MG was 24.8/100 000, and patients with MG had an increased risk of another autoimmune disease compared to controls (22.0% vs. 8.9%; OR: 2.82, 95% CI: 2.49–3.20); this risk was stronger amongst younger persons and women. Polymyositis/dermatomyositis, systemic lupus erythematosus and Addison's disease, three conditions regulated by the HLA‐B8‐DR3 haplotype, were most strongly associated with MG, especially early‐onset disease. HLA typing in the Stockholm MG Cohort showed that early‐onset MG was indeed dominated by HLA‐B8‐DR3. The risk of another autoimmune disease was increased in both patients with MS and siblings of patients with MG, compared to their respective controls, but to a lesser extent than in patients with MG.
Conclusions
Our results suggest that MG shares risk factors with other autoimmune diseases, to a greater degree than MS, with a particular role of the HLA‐B8‐DR3 haplotype, especially amongst younger and female patients.
Background
Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem ...inflammatory syndrome in children (MIS-C) remain elusive.
Objectives
To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C.
Methods
Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured.
Results
We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in
IFNAR1
, underlying autosomal recessive IFNAR1 deficiency.
Conclusions
Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
This roadmap on Nanotechnology for Catalysis and Solar Energy Conversion focuses on the application of nanotechnology in addressing the current challenges of energy conversion: 'high efficiency, ...stability, safety, and the potential for low-cost/scalable manufacturing' to quote from the contributed article by Nathan Lewis. This roadmap focuses on solar-to-fuel conversion, solar water splitting, solar photovoltaics and bio-catalysis. It includes dye-sensitized solar cells (DSSCs), perovskite solar cells, and organic photovoltaics. Smart engineering of colloidal quantum materials and nanostructured electrodes will improve solar-to-fuel conversion efficiency, as described in the articles by Waiskopf and Banin and Meyer. Semiconductor nanoparticles will also improve solar energy conversion efficiency, as discussed by Boschloo et al in their article on DSSCs. Perovskite solar cells have advanced rapidly in recent years, including new ideas on 2D and 3D hybrid halide perovskites, as described by Spanopoulos et al 'Next generation' solar cells using multiple exciton generation (MEG) from hot carriers, described in the article by Nozik and Beard, could lead to remarkable improvement in photovoltaic efficiency by using quantization effects in semiconductor nanostructures (quantum dots, wires or wells). These challenges will not be met without simultaneous improvement in nanoscale characterization methods. Terahertz spectroscopy, discussed in the article by Milot et al is one example of a method that is overcoming the difficulties associated with nanoscale materials characterization by avoiding electrical contacts to nanoparticles, allowing characterization during device operation, and enabling characterization of a single nanoparticle. Besides experimental advances, computational science is also meeting the challenges of nanomaterials synthesis. The article by Kohlstedt and Schatz discusses the computational frameworks being used to predict structure-property relationships in materials and devices, including machine learning methods, with an emphasis on organic photovoltaics. The contribution by Megarity and Armstrong presents the 'electrochemical leaf' for improvements in electrochemistry and beyond. In addition, biohybrid approaches can take advantage of efficient and specific enzyme catalysts. These articles present the nanoscience and technology at the forefront of renewable energy development that will have significant benefits to society.
Young adults are now considered major spreaders of coronavirus disease 2019 (COVID-19) disease. Although most young individuals experience mild to moderate disease, there are concerns of long-term ...adverse health effects. The impact of COVID-19 disease and to which extent population-level immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists in young adults remain unclear.
We conducted a population-based study on humoral and cellular immunity to SARS-CoV-2 and explored COVID-19 disease characteristics in young adults.
We invited participants from the Swedish BAMSE (Barn Children, Allergy Milieu, Stockholm, Epidemiology) birth cohort (age 24-27 years) to take part in a COVID-19 follow-up. From 980 participants (October 2020 to June 2021), we here present data on SARS-CoV-2 receptor-binding domain–specific IgM, IgA, and IgG titers measured by ELISA and on symptoms and epidemiologic factors associated with seropositivity. Further, SARS-CoV-2–specific memory B- and T-cell responses were detected for a subpopulation (n = 108) by ELISpot and FluoroSpot.
A total of 28.4% of subjects were seropositive, of whom 18.4% were IgM single positive. One in 7 seropositive subjects was asymptomatic. Seropositivity was associated with use of public transport, but not with sex, asthma, rhinitis, IgE sensitization, smoking, or body mass index. In a subset of representative samples, 20.7% and 35.0% had detectable SARS-CoV-2 specific B- and T-cell responses, respectively. B- and T-cell memory responses were clearly associated with seropositivity, but T-cell responses were also detected in 17.2% of seronegative subjects.
Assessment of IgM and T-cell responses may improve population-based estimations of SARS-CoV-2 infection. The pronounced surge of both symptomatic and asymptomatic infections among young adults indicates that the large-scale vaccination campaign should be continued.
Summary
Background
We previously reported that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning reduced the cumulative incidence of eczema.
Objective
To ...investigate the impact of feeding LF19 on T‐cell maturation.
Methods
One hundred and seventy‐nine healthy, term infants with no prior allergic manifestations were randomized to daily intake of cereals with (n = 89) or without (n = 90) the addition of LF19 108 colony forming units per serving from 4 to 13 months of age. Venous blood was drawn at 5.5 and 13 months of age. We used the cytokine response to polyclonal T‐cell stimulation by anti‐CD3 plus anti‐CD28 monoclonal antibodies, and in vitro stimulation with the vaccine tetanus toxoid (TT) as measures of global adaptive immunity and capacity to raise a specific T‐cell response, respectively. Expression levels of IL‐2, IFN‐γ, IL‐4, IL‐17A and IL‐10 messenger RNAs (mRNAs) were used as proxies for general T‐cell stimulation and naive Th0 cells, Th1‐, Th2‐, Th17‐ and T regulatory lineages.
Results
There was no difference between the two groups at 5.5 months of age. At 13 months, the polyclonal IL‐2 response was higher in the placebo group (P < 0.05), whereas the IFN‐γ/IL‐2 (P < 0.01) and IL‐17A/IL‐2 (P < 0.05) ratios after polyclonal stimulation were higher in the probiotic group, as was the TT‐specific IL17‐A response (P < 0.001). In both groups, the IFN‐γ and IL‐4 responses increased from 5.5 to 13 months upon both polyclonal and specific stimulation (P < 0.01), whereas the IL‐10 response remained low (P > 0.05).
Conclusion and Clinical Relevance
Our findings suggest modest effects by probiotics on T‐cell maturation following 9 months of probiotic intake. Future studies should address if specific probiotics may drive immune development with possible preventive effects on the development of allergic disease.
The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a ...candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding TACI, in 13 individuals with common variable immunodeficiency. Homozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF. Family members heterozygous with respect to the C104R mutation and individuals with sporadic common variable immunodeficiency who were heterozygous with respect to the amino acid substitutions A181E, S194X and R202H had humoral immunodeficiency. Although signs of autoimmunity and lymphoproliferation are evident, the human phenotype differs from that of the Tnfrsf13b-/- mouse model.
Abstract
We report the application of ancestral sequence reconstruction on coronavirus spike protein, resulting in stable and highly soluble ancestral scaffold antigens (AnSAs). The AnSAs interact ...with plasma of patients recovered from COVID-19 but do not bind to the human angiotensin-converting enzyme 2 (ACE2) receptor. Cryo-EM analysis of the AnSAs yield high resolution structures (2.6–2.8 Å) indicating a closed pre-fusion conformation in which all three receptor-binding domains (RBDs) are facing downwards. The structures reveal an intricate hydrogen-bonding network mediated by well-resolved loops, both within and across monomers, tethering the N-terminal domain and RBD together. We show that AnSA-5 can induce and boost a broad-spectrum immune response against the wild-type RBD as well as circulating variants of concern in an immune organoid model derived from tonsils. Finally, we highlight how AnSAs are potent scaffolds by replacing the ancestral RBD with the wild-type sequence, which restores ACE2 binding and increases the interaction with convalescent plasma.
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