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Introduction Expanded-criteria donors (ECDs) are used to reduce the shortage of kidneys for transplantation. However, kidneys from ECDs are associated with an increased risk of delayed graft function (DGF), a risk factor for allograft loss and mortality. HYPOREME will be a multicentre randomised controlled trial (RCT) comparing targeted hypothermia to normothermia in ECDs, in a country where the use of machine perfusion for organ storage is the standard of care. We hypothesise that hypothermia will decrease the incidence of DGF.Methods and analysis HYPOREME is a multicentre RCT comparing the effect on kidney function in recipients of targeted hypothermia (34°C–35°C) and normothermia (36.5°C–37.5°C) in the ECDs. The temperature intervention starts from randomisation and is maintained until aortic clamping in the operating room. We aim to enrol 289 ECDs in order to analyse the kidney function of 516 recipients in the 53 participating centres. The primary outcome is the occurrence of DGF in kidney recipients, defined as a requirement for renal replacement therapy within 7 days after transplantation (not counting a single session for hyperkalemia during the first 24 hours). Secondary outcomes include the proportion of patients with individual organs transplanted in each group; the number of organs transplanted from each ECD and the vital status and kidney function of the recipients 7 days, 28 days, 3 months and 1 year after transplantation. An interim analysis is planned after the enrolment of 258 kidney recipients.Ethics and dissemination The trial was approved by the ethics committee of the French Intensive Care Society (CE-SRLF-16-07) on 26 April 2016 and by the competent French authorities on 20 April 2016 (Comité de Protection des Personnes-TOURS-Région Centre-Ouest 1, registration #2016-S3). Findings will be published in peer-reviewed journals and presented during national and international scientific meetings.Trial registration number NCT03098706.

Abstract Background Immunoglobulin E (IgE) is the treatment target of omalizumab, a monoclonal antibody indicated in the treatment of severe allergic asthma. Long-term variability of serum total IgE (sIgEtot) in asthmatics remains poorly documented. Methods In this prospective study, sIgEtot levels were measured over 1 year at 7 time points in 41 severe asthmatics treated with high-dose of inhaled corticosteroids and long-acting β2 agonists. 33 patients were atopic based on at least one positive RAST to common aeroallergens. Patients were divided into three groups according to their baseline sIgEtot level: low ( 700 IU/mL; n = 11). Patients also completed the six-item Juniper Asthma Control Questionnaire (ACQ6). The sIgEtot variability and factors predictive for this variability were studied, as well as ACQ6 outcomes. Results The variation in sIgEtot level was mostly the consequence of between patient-variability, which represented 96%, 71% and 96% of the total variability in the low, intermediate and high sIgEtot subgroups, respectively. The residual within-patient variability was therefore limited. In 10/41 patients, sIgEtot levels increased or decreased, for at least one visit, beyond the predefined range of the subgroups to which they were assigned ( 700 IU/mL). There was a significant but weak correlation between sIgEtot and ACQ6 score over all time points (r = 0.15, p = 0.02), but sIgEtot failed to associate with severe exacerbation. sIgEtot decreased by 3% with any additional year of age for the whole group (p = 0.01) and increased by 5% per one unit of allergen exposure score in atopic patients (p = 0.002). Conclusion In severe asthmatics, limited within-patient variability of sIgEtot levels was observed over 1 year as opposed to marked between-subject variability. sIgEtot decreases with age. Variation in sIgEtot weakly associates with asthma control but not with exacerbation.

Background Like other helminths, hookworms (HW) induce a regulatory immune response able to modulate and dampen reactivity of the host to antigens. No data about the evolution of the immune response after treatment are available. We aim to phenotype the regulatory immune response during natural HW infection and its evolution after treatment. Methodology Twenty hookworm infected (HW+) and 14 non-infected subjects HW–from endemic area in the periphery of Ho Chi Minh City were included. Blood and feces samples were obtained before, 2 and 4 weeks after treatment with Albendazole 400mg. Additional samples were obtained at 3 and 12 months in the HW+ group. Hematological parameters, Treg (CD4+CD25hiFoxP3hi) and surface molecules (CD39, CD62L, ICOS, PD-1, CD45RA) were measured as well as inflammatory and lymphocytes differentiation cytokines such as IL-1β, IL-6, IFNγ, IL-4, IL-17, IL-10, IL-2 and TGFβ. Results HW+ subjects showed higher Treg, TregICOS+, Treg PD1-, TregCD62L+ and CD45RA+FoxP3lo resting Treg (rTreg). CD45RA-FoxP3lo non-suppressive Treg cells were also increased. No preferential Th1/Th2 orientation was observed, nor difference for IL-10 between two groups. After treatment, Treg, TregICOS+, TregCD62L+, Treg PD1- and rTreg decreased while IL-4 and IL-6 cytokines increased. Conclusion During HW infection, Treg are increased and characterized by a heterogeneous population: a highly suppressive as well as a non-suppressive T cells phenotype. After treatment, Treg with immune-suppressive phenotype exhibited a decrease parallel to an inflammatory Th2 response.

BackgroundIgE characterizes the humoral response of allergic sensitization but less is known about what modulates its function and why some patients present clinical symptoms for a given IgE level and others do not. An IgE response also occurs during helminth diseases, independently of allergic symptoms. This response could be a model of non-functional IgE.ObjectiveTo study the IgE response against environmental allergens induced during natural helminth infection.MethodsIn 28 non allergic subjects from the periphery of Ho Chi Minh city with (H+, n = 18) and without helminth infection (H-, n = 10), we measured IgE and IgG4 against several components of Dermatophagoïdes pteronyssinus (Dpt) and Ascaris (a marker of immunization against nematodes), and determined the IgE component sensitization profile using microarray ISAC biochips. The functional ability of IgE to induce degranulation of cultured mast cells was evaluated in the presence of Dpt.ResultsNon allergic H+ subjects exhibited higher levels of IgE against Dpt compared to H- subjects. Dpt IgE were not functional in vitro and did not recognize usual Dpt major allergens. IgE recognized other component allergens that belong to different protein families, and most were glycosylated. Depletion of IgE recognizing carbohydrate cross-reactive determinant (CCD) did not induce a reduction in Dpt IgE. The Dpt IgG4 were not significantly different.ConclusionHelminth infections induced IgE against allergens such as Dpt and molecular components that belong to different sources as well as against CCD (such as β-1,2-xylose and/or ⍺-1,3-fucose substituted N-glycans). Dpt IgE were not able to induce degranulation of mast cells and were not explained by sensitization to usual major allergens or N-glycans.

Background: Rapid urbanization combined with rural migration to urban areas in southern Vietnam could be risk factors for allergen sensitization, contributing to chronic respiratory diseases (CRD). We aimed to evaluate the prevalence of mite sensitization and its relation to house dust characteristics among rural and urban native and migrating populations with CRD. Methods: Rural (n = 19) and urban (n = 46) dwellings were defined on the basis of a home typology. Controls were western Belgian houses (n = 14). Besides the house characteristics, both endotoxin and mite allergens were measured in the settled dusts. The sensitization to mite allergens was defined by positive skin prick test (SPT) and concentration of specific IgE (sIgE)≥ 0.7 U/mL. The prevalence of mite sensitization was evaluated among 610 patients with CRD and compared according to both their home types and places of birth and residences. Results: The concentration of endotoxin (but not mite allergen) was higher in rural compared to urban dusts (440 (95%CI: 314–566) versus 170 (95%CI: 115–226) EU/mg; p