In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of ...autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90% Foxp3(+). We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects.
The AEḡIS collaboration's main goal is to measure the acceleration of antihydrogen (H¯) due to gravity. The experimental scheme is to form a pulsed beam whose vertical deflection is then measured by ...means of a moiré deflectometer 1. Creating pulsed H¯ is crucial since it allows a velocity measurement of the antiatoms via time of flight (ToF) necessary to deduce the gravitational acceleration ḡ from the vertical deflection Δs. The aim of this article is to outline the experimental protocol leading up to pulsed antihydrogen production in the AEḡIS experiment.
The efficient production of cold antihydrogen atoms in particle traps at CERN's Antiproton Decelerator has opened up the possibility of performing direct measurements of the Earth's gravitational ...acceleration on purely antimatter bodies. The goal of the AEgIS collaboration is to measure the value of g for antimatter using a pulsed source of cold antihydrogen and a Moiré deflectometer/Talbot-Lau interferometer. The same antihydrogen beam is also very well suited to measuring precisely the ground-state hyperfine splitting of the anti-atom. The antihydrogen formation mechanism chosen by AEgIS is resonant charge exchange between cold antiprotons and Rydberg positronium. A series of technical developments regarding positrons and positronium (Ps formation in a dedicated room-temperature target, spectroscopy of the n = 1–3 and n = 3–15 transitions in Ps, Ps formation in a target at 10K inside the 1T magnetic field of the experiment) as well as antiprotons (high-efficiency trapping of p̅, radial compression to sub-millimetre radii of mixed e⁻/p̅ plasmas in 1T field, high-efficiency transfer of p̅ to the antihydrogen production trap using an in-flight launch and recapture procedure) were successfully implemented. Two further critical steps that are germane mainly to charge exchange formation of antihydrogen—cooling of antiprotons and formation of a beam of antihydrogen—are being addressed in parallel. The coming of ELENA will allow, in the very near future, the number of trappable antiprotons to be increased by more than a factor of 50. For the antihydrogen production scheme chosen by AEgIS, this will be reflected in a corresponding increase of produced antihydrogen atoms, leading to a significant reduction of measurement times and providing a path towards high-precision measurements. This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.
This correction provides updated acknowledgements:
This work was supported by Istituto Nazionale di Fisica Nucleare; the Swiss National Science Foundation Ambizione Grant (No. 154833); a Deutsche ...Forschungsgemeinschaft research grant; an excellence initiative of Heidelberg University; Marie Sklodowska-Curie Innovative Training Network Fellowship of the European Commission’s Horizon 2020 Programme (No. 721559 AVA); European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement ANGRAM No 748826; European Research Council under the European Union’s Seventh Framework Program FP7/2007-2013 (Grants Nos. 291242 and 277762); Austrian Ministry for Science, Research, and Economy; Research Council of Norway; Bergen Research Foundation; John Templeton Foundation; Ministry of Education and Science of the Russian Federation and Russian Academy of Sciences; and the European Social Fund within the framework of realizing the project, in support of intersectoral mobility and quality enhancement of research teams at Czech Technical University in Prague (Grant No. CZ.1.07/2.3.00/30.0034).
This correction provides updated acknowledgements:This work was supported by Istituto Nazionale di Fisica Nucleare; the Swiss National Science Foundation Ambizione Grant (No. 154833); a Deutsche ...Forschungsgemeinschaft research grant; an excellence initiative of Heidelberg University; Marie Sklodowska-Curie Innovative Training Network Fellowship of the European Commission’s Horizon 2020 Programme (No. 721559 AVA); European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement ANGRAM No 748826; European Research Council under the European Union’s Seventh Framework Program FP7/2007-2013 (Grants Nos. 291242 and 277762); Austrian Ministry for Science, Research, and Economy; Research Council of Norway; Bergen Research Foundation; John Templeton Foundation; Ministry of Education and Science of the Russian Federation and Russian Academy of Sciences; and the European Social Fund within the framework of realizing the project, in support of intersectoral mobility and quality enhancement of research teams at Czech Technical University in Prague (Grant No. CZ.1.07/2.3.00/30.0034).
The weak equivalence principle states that the motion of a body in a gravitational field is independent of its structure or composition. This postulate of general relativity has been tested to very ...high precision with ordinary matter, but no relevant experimental verification with antimatter has ever been carried out. The AEGIS experiment will measure the gravitational acceleration of antihydrogen to ultimately 1% precision. For this purpose, a pulsed horizontal antihydrogen beam with a velocity of several 100 m s−1 will be produced. Its vertical deflection due to gravity will be detected by a setup consisting of material gratings coupled with a position-sensitive detector, operating as a moiré deflectometer or an atom interferometer. The AEGIS experiment is installed at CERN’s Antiproton Decelerator, currently the only facility in the world which produces copious amounts of low-energy antiprotons. The construction of the setup has been going on since 2010 and is nearing completion. A proof-of-principle experiment with antiprotons has demonstrated that the deflection of antiparticles by a few μm due to an external force can be detected. Technological and scientific development pertaining to specific challenges of the experiment, such as antihydrogen formation by positronium charge exchange or the position-sensitive detection of antihydrogen annihilations, is ongoing.
The AEgIS experiment aims at producing antihydrogen (and eventually measuring the effects of the Earth gravitational field on it) with a method based on the charge exchange reaction between ...antiproton and Rydberg positronium. To be precise, antiprotons are delivered by the CERN Antiproton Decelerator (AD) and are trapped in a multi-ring Penning trap, while positronium is produced by a nanoporous silica target and is excited to Rydberg states by means of a two steps laser excitation. New Monte Carlo simulations are presented in this paper in order to investigate the current status of the AEgIS experiment
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and to interpret the recently collected data
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Purpose
Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established ...sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.
Methods
We conducted a longitudinal study of 15 lupus patients (14 with SLE and one with discoid LE) treated with ivIg in cycles of 2–6 consecutive monthly infusions. Among these 15 patients, 10 responded to ivIg therapy with clear clinical improvement. We characterized Tregs and determined TCR spectratypes of four Vβ families with reported oligoclonality. Cell counts, cytometry and TCR spectratypes were obtained from peripheral blood at various time points before, during and after ivIg treatment. T-cell oligoclonality was assessed as Vβ-familywise repertoire perturbation, calculated for each patient in respect to an individual reference profile averaged over all available time points.
Results
For 11 out of 15 patients, average Vβ1/Vβ2/Vβ11/Vβ14 repertoires were less perturbed under than outside ivIg therapy. The four exceptions with relatively increased average perturbation during ivIg therapy included three patients who failed to respond clinically to an ivIg therapy cycle. Patients' Treg CD25 surface density (cytometric MFI) was clearly reduced when compared to healthy controls, but not obviously influenced by ivIg. However, patients' average Treg CD25 MFI was found negatively correlated with both Vβ11 and Vβ14 perturbations measured under ivIg therapy.
Conclusions
This indicates a role of active Tregs in the therapeutic effect of ivIg.
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