Diet during pregnancy and infancy, and risk of allergic or autoimmune disease: a systematic review and meta-analysis

Background: There is uncertainty about the influence of diet during pregnancy and infancy on a child’s immune development. We assessed whether variations in maternal or infant diet can influence risk of allergic or autoimmune disease. Methods and findings: Two authors selected studies, extracted data, and assessed risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) between January 1946 and July 2013 for observational studies and until December 2017 for intervention studies that evaluated the relationship between diet during pregnancy, lactation, or the first year of life and future risk of allergic or autoimmune disease. We identified 260 original studies (964,143 participants) of milk feeding, including 1 intervention trial of breastfeeding promotion, and 173 original studies (542,672 participants) of other maternal or infant dietary exposures, including 80 trials of maternal (n = 26), infant (n = 32), or combined (n = 22) interventions. Risk of bias was high in 125 (48%) milk feeding studies and 44 (25%) studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with nonpathogenic micro-organisms (probiotics) during late pregnancy and lactation may reduce risk of eczema (Risk Ratio [RR] 0.78; 95% CI 0.68–0.90; I2 = 61%; Absolute Risk Reduction 44 cases per 1,000; 95% CI 20–64), and 6 trials suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitisation to egg (RR 0.69, 95% CI 0.53–0.90; I2 = 15%; Absolute Risk Reduction 31 cases per 1,000; 95% CI 10–47). GRADE certainty of these findings was moderate. We found weaker support for the hypotheses that breastfeeding promotion reduces risk of eczema during infancy (1 intervention trial), that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus (28 observational studies), and that probiotics reduce risk of allergic sensitisation to cow’s milk (9 intervention trials), where GRADE certainty of findings was low. We did not find that other dietary exposures—including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake—influence risk of allergic or autoimmune disease. For many dietary exposures, data were inconclusive or inconsistent, such that we were unable to exclude the possibility of important beneficial or harmful effects. In this comprehensive systematic review, we were not able to include more recent observational studies or verify data via direct contact with authors, and we did not evaluate measures of food diversity during infancy. Conclusions: Our findings support a relationship between maternal diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitisation to food, respectively

DQB1*0602 rather than DRB1*1501 confers susceptibility to multiple sclerosis-like disease induced by proteolipid protein (PLP)

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), myelin oligodendrocyte protein (MOG). MS is a complex trait whereby the HLA genes, particularly class-II genes of HLA-DR15 haplotype, dominate the genetic contribution to disease-risk. Due to strong linkage disequilibrium in HLA-II region, it has been hard to establish precisely whether the functionally relevant effect derives from the DRB1*1501, DQA1*0102-DQB1*0602, or DRB5*0101 loci of HLA-DR15 haplotype, their combinations, or their epistatic interactions. Nevertheless, most genetic studies have indicated DRB1*1501 as a primary risk factor in MS. Here, we used 'HLA-humanized' mice to discern the potential relative contribution of DRB1*1501 and DQB1*0602 alleles to susceptibility to "humanized" MS-like disease induced by PLP, one of the most prominent and encephalitogenic target-antigens implicated in human MS.</p> <p>Methods</p> <p>The HLA-DRB1*1501- and HLA-DQB1*0602-Tg mice (MHC-II^-/-), and control non-HLA-DR15-relevant-Tg mice were immunized with a set of overlapping PLP peptides or with recombinant soluble PLP for induction of "humanized" MS-like disease, as well as for ex-vivo analysis of immunogenic/immunodominant HLA-restricted T-cell epitopes and associated cytokine secretion profile.</p> <p>Results</p> <p>PLP autoimmunity in both HLA-DR15-Tg mice was focused on 139-151 and 175-194 epitopes. Strikingly, however, the HLA-DRB1*1501-transgenics were refractory to disease induction by any of the overlapping PLP peptides, while HLA-DQB1*0602 transgenics were susceptible to disease induction by PLP139-151 and PLP175-194 peptides. Although both transgenics responded to both peptides, the PLP139-151- and PLP175-194-reactive T-cells were directed to Th1/Th17 phenotype in DQB1*0602-Tg mice and towards Th2 in DRB1*1501-Tg mice.</p> <p>Conclusions</p> <p>While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS. Moreover, that DQB1*0602, but not DRB1*1501, determines disease-susceptibility to PLP in HLA-transgenics, suggests a potential differential, functional role for DQB1*0602 as a predisposing allele in MS. This, together with previously demonstrated disease-susceptibility to MBP and MOG in DRB1*1501-transgenics, also suggests a differential role for DRB1*1501 and DQB1*0602 depending on target antigen and imply a potential complex 'genotype/target antigen/phenotype' relationship in MS heterogeneity.</p

Charge identification of fragments with the emulsion spectrometer of the FOOT experiment

The FOOT (FragmentatiOn Of Target) experi- ment is an international project designed to carry out the fragmentation cross-sectional measurements relevant for charged particle therapy (CPT), a technique based on the use of charged particle beams for the treatment of deep-seated tumors. The FOOT detector consists of an electronic setup for the identification of Z &gt;= 3 fragments and an emulsion spectrometer for Z &lt;= 3 fragments. The first data taking was performed in 2019 at the GSI facility(Darmstadt, Germany). In this study, the charge identifi-cation of fragments induced by exposing an emulsion detector, embedding a C2H4 target, to an oxygen ion beam of 200 MeV/n is discussed. The charge identifica-tion is based on the controlled fading of nuclear emulsions in order to extend their dynamic range in the ionization response

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

Elemental fragmentation cross sections for a O-16 beam of 400 MeV/u kinetic energy interacting with a graphite target using the FOOT Delta E-TOF detectors

The study of nuclear fragmentation plays a central role in many important applications: from the study of Particle Therapy (PT) up to radiation protection for space (RPS) missions and the design of shielding for nuclear reactors. The FragmentatiOn Of Target (FOOT) collaboration aims to study the nuclear reactions that describe the interactions with matter of different light ions (like H-1, He-4, C-12, O-16) of interest for such applications, performing double differential fragmentation cross section measurements in the energy range of interest for PT and RPS. In this manuscript, we present the analysis of the data collected in the interactions of an oxygen ion beam of 400 MeV/u with a graphite target using a partial FOOT setup, at the GSI Helmholtz Center for Heavy Ion Research facility in Darmstadt. During the data taking the magnets, the silicon trackers and the calorimeter foreseen in the final FOOT setup were not yet available, and hence precise measurements of the fragments kinetic energy, momentum and mass were not possible. However, using the FOOT scintillator detectors for the time of flight (TOF) and energy loss (Delta E) measurements together with a drift chamber, used as beam monitor, it was possible to measure the elemental fragmentation cross sections. The reduced detector set-up and the limited available statistics allowed anyway to obtain relevant results, providing statistically significant measurements of cross sections eagerly needed for PT and RPS applications. Whenever possible the obtained results have been compared with existing measurements helping in discriminating between conflicting results in the literature and demonstrating at the same time the proper functioning of the FOOT Delta E-TOF system. Finally, the obtained fragmentation cross sections are compared to the Monte Carlo predictions obtained with the FLUKA software

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air (R) App

Background In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. Methods All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. Results A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. Conclusions VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.Peer reviewe

Guidance to 2018 good practice : ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma

AimsMobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases.MethodsMASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients.StakeholdersInclude patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors.ResultsMASK is deployed in 23 countries and 17 languages. 26,000 users have registered.EU grants (2018)MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour).Lessons learnt(i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.Peer reviewe

Haematopoietic stem cell transplantation for severe autoimmune diseases in children : a review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (<18 years) for a range of AD indications. HSCT is a promising treatment modality, with potential long-term disease control or cure, but therapy-related morbidity and mortality need to be reduced. Further research is warranted to establish the position of HSCT in paediatric ADs via registries and prospective clinical studies to support evidence-based interspeciality guidelines and recommendations