Cardiac arrest patients have an impaired immune response, which is not influenced by induced hypothermia

Induced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest. A prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined. In total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C. Patients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest. ClinicalTrials.gov NCT01020916, registered 25 November 200

Pathogenic NFKB2 variant in the ankyrin repeat domain (R635X) causes a variable antibody deficiency.

Genetic studies are identifying an increasing number of monogenic causes of Common Variable Immunodeficiency (CVID). Pathogenic variants in the C-terminus of NFKB2 have been identified in the subset of CVID patients whose immunodeficiency is associated with ectodermal dysplasia and central adrenal insufficiency. We describe 2 unrelated CVID pedigrees with 4 cases of pathogenic stop gain variants (c.1903C > T) in the ankyrin repeat domain (ARD) of NF-κB2, leading to a premature truncation of the protein at p.Arg635Term (R635X). By immunophenotyping and functional ex vivo B- and T-cell experiments we characterized the variant by reduced class-switched memory B-cell counts and immature plasmablasts, unable to produce IgG and IgA. Features of a poor proliferative T-cell response and reduced expansion of CD4+CXCR5+ T cells was only observed in the two clinically affected index cases without any clear clinical correlate. In conclusion, pathogenic stop variants in the ARD of NFKB2 can cause 'infection-only' CVID with an abnormal B-cell phenotype and a variable clinical penetrance

Loss of function NFKB1 variants are the most common monogenic cause of CVID in Europeans.

BACKGROUND: The genetic etiology of primary immunodeficiency disease (PID) carries prognostic information. OBJECTIVE: We conducted a whole-genome sequencing study assessing a large proportion of the NIHR-BioResource - Rare Disease cohort. METHODS: In the predominantly European study population of principally sporadic unrelated PID cases (n=846), a novel Bayesian method identified NFKB1 as one most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n=390) in the cohort. Amino-acid substitutions predicted to be pathogenic were assessed by analysis of structural protein data. Immunophenotyping, immunoblotting and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype co-segregation analyses. RESULTS: Both sporadic and familial cases demonstrated evidence of the non-infective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%) and autoimmune disease (48%), features prior studies correlate with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B lymphocyte differentiation. Detailed assessment of B lymphocyte numbers, phenotype and function identifies the presence of a raised CD21lowB cell population: combined with identification of the disease-causing variant, this distinguishes between healthy individuals, asymptomatic carriers and clinically affected cases. CONCLUSION: We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID that results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.This study was supported by The National Institute for Health Research England (grant number RG65966), and by the Center of Immunodeficiencies Amsterdam (CIDA). JET is supported by an MRC Clinician Scientist Fellowship (MR/L006197/1). AJT is supported by both the Wellcome Trust (104807/Z/14/Z) and by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. EO receives personal fees from CSL Behring and MSD

Bibliometric delineation of scientific fields

International audienceDelineation of scientific domains (fields, areas of science) is a prior task in bibliometric studies at the meso-level, far from straightforward in domains with high multidisciplinarity, variety and instability. The Context section shows the connection of delineation problem to the question of disciplines vs. invisible colleges, through three combinable models: ready-made classifications of science, classical information retrieval searches, mapping and clustering. They differ in the role and modalities of supervision. The Tools section sketches various bibliometric techniques on the background of information retrieval, data analysis, network theory, showing both their power and their limitations in delineation processes. The role and modalities of supervision are emphasized. The section Multiple Networks and Hybridization addresses the comparison and combination of bibliometric networks (actors, texts, citations) and the various ways of hybridization. In the concluding section, typical protocols and further questions are proposed

J/ψ elliptic flow in Pb-Pb collisions at √s NN =2.76 TeV

We report on the first measurement of inclusive J/psi elliptic flow v(2) in heavy-ion collisions at the LHC. The measurement is performed with the ALICE detector in Pb-Pb collisions at root s(NN) = 2.76 TeV in the rapidity range 2.5 < y < 4.0. The dependence of the J/psi v(2) on the collision centrality and on the J/psi transverse momentum is studied in the range 0 <= p(T) < 10 GeV/c. For semicentral Pb-Pb collisions at root s(NN) = 2.76 TeV, an indication of nonzero v(2) is observed with a largest measured value of v(2) = 0.116 +/-0.046(stat) +/- 0.029(syst) for J/psi in the transverse momentum range 2 <= p(T) < 4 GeV/c. The elliptic flow measurement complements the previously reported ALICE results on the inclusive J/psi nuclear modification factor and favors the scenario of a significant fraction of J/psi production from charm quarks in a deconfined partonic phase

Suppression of high transverse momentum D mesons in central Pb-Pb collisions at root s(NN)=2.76 TeV

The production of the prompt charm mesons D-0, D+, D*(+), and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at the LHC, at a centre-of-mass energy root s(NN) = 2.76 TeV per nucleon-nucleon collision. The p(t)-differential production yields in the range 2 < p(t) < 16 GeV/c at central rapidity, vertical bar y vertical bar < 0.5, were used to calculate the nuclear modification factor R-AA with respect to a proton-proton reference obtained from the cross section measured at root s = 7 TeV and scaled to root s = 2.76 TeV. For the three meson species, R-AA shows a suppression by a factor 3-4, for transverse momenta larger than 5 GeV/c in the 20% most central collisions. The suppression is reduced for peripheral collisions