The Role of Extracellular Vesicles in Allergic Sensitization: A Systematic Review.

Allergies affect approximately 10-30% of people worldwide, with an increasing number of cases each year; however, the underlying mechanisms are still poorly understood. In recent years, extracellular vesicles (EVs) have been suggested to play a role in allergic sensitization and skew to a T helper type 2 (Th2) response. The aim of this review is to highlight the existing evidence of EV involvement in allergies. A total of 22 studies were reviewed; 12 studies showed EVs can influence a Th2 response, while 10 studies found EVs promoted a Th1 or Treg response. EVs can drive allergic sensitization through up-regulation of pro-Th2 cytokines, such as IL-4 and IL-13. In addition, EVs from MRSA can induce IgE hypersensitivity in mice towards MRSA. On the other hand, EVs can induce tolerance in the immune system; for example, pre-exposing OVA-loaded EVs prevented OVA sensitization in mice. The current literature thus suggests that EVs play an essential role in allergy. Further research utilizing human in vitro models and clinical studies is needed to give a reliable account of the role of EVs in allergy.

The Role of Extracellular Vesicles in Atopic Dermatitis.

Atopic dermatitis, or eczema, is the most common chronic skin disorder, characterized by red and pruritic lesions. Its etiology is multifaceted, involving an interplay of factors, such as the allergic immune response, skin barrier dysfunction, and dysbiosis of the skin microbiota. Recent studies have explored the role of extracellular vesicles (EVs), which are lipid bilayer-delimitated particles released by all cells, in atopic dermatitis. Examination of the available literature identified that most studies investigated EVs released by Staphylococcus aureus, which were found to impact the skin barrier and promote the release of cytokines that contribute to atopic dermatitis development. In addition, EVs released by the skin fungus, Malassezia sympodialis, were found to contain allergens, suggesting a potential contribution to allergic sensitization via the skin. The final major finding was the role of EVs released by mast cells, which were capable of activating various immune cells and attenuating the allergic response. While research in this area is still in its infancy, the studies examined in this review provide encouraging insights into how EVs released from a variety of cells play a role in both contributing to and protecting against atopic dermatitis.

Invariant NKT cells are more abundant in peanut-allergic adults and a subset of CD8+ iNKT cells are depleted after peanut oil exposure.

Introduction: Peanut allergy is one of the most prevalent food allergies globally. Currently, most research into the mechanisms involved in protein allergy focuses on the protein allergens under investigation, and information on the function of accompanying compounds, such as lipids, is scarce. Thus, this research investigates the role of peanut-associated lipids and invariant natural killer T (iNKT) cells in peanut allergy using a novel, human, in vitro assay. Methods: PBMCs from non-allergic and peanut-allergic subjects were stimulated with the glycolipid, α-Galactosylceramide (α-GalCer), over 14 days for iNKT cell expansion. Autologous dendritic cells (DCs) were stimulated with either peanut oil, the lipid-binding peanut allergen, Ara h 8, or both peanut oil and Ara h 8. The expanded iNKT cells were then immunomagnetically isolated and co-cultured for 5 h with autologous DCs, and cytokine expression was measured by flow cytometry. Results: A 5-fold higher iNKT cell population was observed in peanut-allergic subject peripheral blood compared to non-allergic controls. In all subjects, conventional flow analysis highlighted iNKTs co-cultured with autologous α-GalCer-pulsed DCs displayed increased IL-4 and IFN-y secretion within 5 hours of co-culture. A 10-parameter unsupervised clustering analysis of iNKT phenotype found significantly more CD3+CD8+CD25+IL-4+IL-5+IL-10+IFNγ+ cells in non-allergic adults following culture with peanut oil. Conclusion: For the first time, we show iNKT cells are more abundant in peanut-allergic adults compared to non-allergic adults, and peanut lipid-exposed iNKT cells resulted in the identification of a subset of CD8+ iNKT cells which was significantly lower in peanut-allergic adults. Thus, this study proposes a role for iNKT cells and peanut allergen-associated lipids in peanut allergy.

Conducting school-based health surveys with secondary schools in England: advice and recommendations from school staff, local authority professionals, and wider key stakeholders, a qualitative study.

BACKGROUND: Improving the health and well-being of young people is a public health priority. Schools present an ideal setting to implement strategies to improve young people's health and well-being. A key strategy involves conducting surveys to assess student health needs, inform interventions, and monitor health over time. Conducting research in schools is, however, challenging. Schools can find it difficult to participate and adhere to research processes, even when they are keen to be involved in research, because of competing priorities (e.g., attendance and educational achievement), as well as time and resource constraints. There is a lack of literature on the perspectives of school staff and other key stakeholders working in young people's health on how best to work with schools to conduct health research, and in particular, health surveys. METHODS: Participants (n = 26) included members of staff from 11 secondary schools (covering students aged 11-16 years), 5 local authority professionals, and 10 wider key stakeholders in young people's health and well-being (e.g., a school governor, a national government member), based in South West England. Participants took part in semi-structured interviews that were conducted either over the phone or via an online platform. Data were analysed using the Framework Method. RESULTS: Three main themes were identified: Recruitment and Retention, Practicalities of Data Collection in Schools, and Collaboration from Design to Dissemination. It is important to acknowledge the role of local authorities and academy trusts in the English education system, and work closely with these when conducting school-based health surveys. School staff prefer to be contacted about research via email and in the summer term, following exams. Researchers should contact a member of staff involved in student health/well-being, as well as senior leadership, during recruitment. Data collection during the start and end of the school year is undesirable. Research should be collaborative with school staff and young people, consistent with school priorities and values, and flexible and tailored to school timetables and resources. CONCLUSIONS: Overall the findings demonstrate that survey-based research methods should be school-led and tailored to each school.

Implementing a regional school health research network in england to improve adolescent health and well-being, a qualitative process evaluation.

BACKGROUND: There is an increased need for prevention and early intervention surrounding young people's health and well-being. Schools offer a pivotal setting for this with evidence suggesting that focusing on health within schools improves educational attainment. One promising approach is the creation of School Health Research Networks which exist in Wales and Scotland, but are yet to be developed and evaluated in England. METHODS: This qualitative process evaluation aimed to identify the main barriers and facilitators to implementing a pilot School Health Research Network in the South West of England (SW-SHRN). Semi-structured interviews were conducted with school staff, local authority members, and other key stakeholders. Interview data were analysed using the 7-stage framework analysis approach. RESULTS: Four main themes were identified from the data: (1) 'Key barriers to SW-SHRN' (competing priorities of academic attainment and well-being, schools feeling overwhelmed with surveys and lack of school time and resource); (2) 'Key facilitators to SW-SHRN: providing evidence-based support to schools' (improved knowledge to facilitate change, feedback reports and benchmarking and data to inform interventions); (3) 'Effective dissemination of findings' (interpretation and implementation, embedding findings with existing evidence and policy, preferences for an online platform as well personalised communication and the importance of involving young people and families); and (4) 'Longer-term facilitators: ensuring sustainability' (keeping schools engaged, the use of repeat surveys to evaluate impact, informing school inspection frameworks and expanding reach of the network). CONCLUSION: This study identifies several barriers to be addressed and facilitators to be enhanced in order to achieve successful implementation of School Health Research Networks in England which include providing a unique offering to schools that is not too burdensome, supporting schools to take meaningful action with their data and to work closely with existing organisations, services and providers to become meaningfully embedded in the system.

Using systems thinking to understand how the South West - School Health Research Network can improve adolescent health and well-being: A qualitative process evaluation.

Schools offer a valuable setting to promote good health and mental well-being amongst young people. Schools are complex systems and therefore systems interventions are needed to improve pupil health and well-being. This paper presents a qualitative process evaluation of the South West- School Health Research Network, a systems level intervention. The evaluation is based on interviews with school staff, local authorities and wider stakeholders. Given the complexity of England's educational system there is a need to intervene and monitor health at multiple levels and to ensure close partnership working to effectively improve adolescent health through schools.

Humoral and cellular immunity in patients with rare autoimmune rheumatic diseases following SARS-CoV-2 vaccination.

OBJECTIVES: Coronavirus 2019 vaccine responses in rare autoimmune rheumatic diseases (RAIRDs) remain poorly understood; in particular there is little known about whether people develop effective T cell responses. We conducted an observational study to evaluate the short-term humoral and cell-mediated T cell response after the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in RAIRD patients compared with healthy controls (HCs). METHODS: Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2-specific T cell responses were measured and compared with those of HCs. Activation-induced marker and deep phenotyping assays were used to identify differences in T cells between high and no/low antibody groups, followed by multidimensional clustering. RESULTS: A total of 50 patients with RAIRDs were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). The median anti-spike levels were significantly lower in RAIRD patients compared with HCs (P < 0.0001). Fifteen (33%) patients had undetectable levels and 26 (57%) had levels lower than the lowest HC. Rituximab in the last 12 months (P = 0.003) was associated with reduced immunogenicity compared with a longer pre-vaccination period. There was a significant difference in B cell percentages (P = 0.03) and spike-specific CD4+ T cells (P = 0.02) between no/low antibody vs high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells. CONCLUSIONS: Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with no/low antibodies have diminished numbers and poor quality of memory T cells that lack proliferative and functional capacities.

Antibody response to four doses of SARS-CoV-2 vaccine in rare autoimmune rheumatic diseases: an observational study.

Objective: Antibody responses to coronavirus disease 2019 (COVID-19) vaccines are reduced among immunocompromised patients but are not well quantified among people with rare disease. We conducted an observational study to evaluate the antibody responses to the booster SARS-CoV-2 vaccine in people with rare autoimmune rheumatic diseases (RAIRD). Methods: Blood samples were collected after second, before third, after third and after fourth vaccine doses. Anti-spike and anti-nucleocapsid antibody levels were measured using an in-house ELISA. Logistic regression models were built to determine the predictors for non-response. Results were compared with age- and sex-matched healthy controls. Results: Forty-three people with RAIRD were included, with a median age of 56 years. Anti-spike seropositivity increased from 42.9% after second dose to 51.2% after third dose and 65.6% after fourth dose. Median anti-spike antibody levels increased from 33.6 (interquartile range 7.8-724.5) binding antibody units after second dose to 239.4 (interquartile range 35.8-1051.1) binding antibody units after the booster dose (third dose, or fourth dose if eligible). Of the participants who had sufficient antibody levels post-second dose, 22.2% had insufficient levels after the booster, and 34.9% of participants had lower antibodies after the booster than the lowest healthy control had after the second dose. Rituximab in the 6 months prior to booster (P = 0.02) and non-White ethnicity (P = 0.04) were associated with non-response. There was a dose-response relationship between the timing of rituximab and generation of sufficient antibodies (P = 0.03). Conclusion: Although the booster dose increased anti-spike IgG and seropositivity rates, some people with RAIRD, particularly those on rituximab, had insufficient antibody levels despite three or four doses.

The Role of Lipids in Allergic Sensitization: A Systematic Review.

Background: Immunoglobulin E (IgE)-mediated allergies are increasing in prevalence, with IgE-mediated food allergies currently affecting up to 10% of children and 6% of adults worldwide. The mechanisms underpinning the first phase of IgE-mediated allergy, allergic sensitization, are still not clear. Recently, the potential involvement of lipids in allergic sensitization has been proposed, with reports that they can bind allergenic proteins and act on immune cells to skew to a T helper type 2 (Th2) response. Objectives: The objective of this systematic review is to determine if there is strong evidence for the role of lipids in allergic sensitization. Methods: Nineteen studies were reviewed, ten of which were relevant to lipids in allergic sensitization to food allergens, nine relevant to lipids in aeroallergen sensitization. Results: The results provide strong evidence for the role of lipids in allergies. Intrinsic lipids from allergen sources can interact with allergenic proteins to predominantly enhance but also inhibit allergic sensitization through various mechanisms. Proposed mechanisms included reducing the gastrointestinal degradation of allergenic proteins by altering protein structure, reducing dendritic cell (DC) uptake of allergenic proteins to reduce immune tolerance, regulating Th2 cytokines, activating invariant natural killer T (iNKT) cells through CD1d presentation, and directly acting upon toll-like receptors (TLRs), epithelial cells, keratinocytes, and DCs. Conclusion: The current literature suggests intrinsic lipids are key influencers of allergic sensitization. Further research utilising human relevant in vitro models and clinical studies are needed to give a reliable account of the role of lipids in allergic sensitization.