| 1. |
- Aoun, M., et al.
(författare)
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Antigen-presenting autoreactive B cells activate regulatory T cells and suppress autoimmune arthritis in mice
- 2023
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Ingår i: Journal of Experimental Medicine. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 0022-1007 .- 1540-9538. ; 220:11
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Tidskriftsartikel (refereegranskat)abstract
- B cells undergo several rounds of selection to eliminate potentially pathogenic autoreactive clones, but in contrast to T cells, evidence of positive selection of autoreactive B cells remains moot. Using unique tetramers, we traced natural autoreactive B cells (C1-B) specific for a defined triple-helical epitope on collagen type-II (COL2), constituting a sizeable fraction of the physiological B cell repertoire in mice, rats, and humans. Adoptive transfer of C1-B suppressed arthritis independently of IL10, separating them from IL10-secreting regulatory B cells. Single-cell sequencing revealed an antigen processing and presentation signature, including induced expression of CD72 and CCR7 as surface markers. C1-B presented COL2 to T cells and induced the expansion of regulatory T cells in a contact-dependent manner. CD72 blockade impeded this effect suggesting a new downstream suppressor mechanism that regulates antigen-specific T cell tolerization. Thus, our results indicate that autoreactive antigen-specific naive B cells tolerize infiltrating T cells against self-antigens to impede the development of tissue-specific autoimmune inflammation.
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| 4. |
- Dimmock, Andrew P., et al.
(författare)
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Modeling the Geomagnetic Response to the September 2017 Space Weather Event Over Fennoscandia Using the Space Weather Modeling Framework : Studying the Impacts of Spatial Resolution
- 2021
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Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- We must be able to predict and mitigate against geomagnetically induced current (GIC) effects to minimize socio-economic impacts. This study employs the space weather modeling framework (SWMF) to model the geomagnetic response over Fennoscandia to the September 7-8, 2017 event. Of key importance to this study is the effects of spatial resolution in terms of regional forecasts and improved GIC modeling results. Therefore, we ran the model at comparatively low, medium, and high spatial resolutions. The virtual magnetometers from each model run are compared with observations from the IMAGE magnetometer network across various latitudes and over regional-scales. The virtual magnetometer data from the SWMF are coupled with a local ground conductivity model which is used to calculate the geoelectric field and estimate GICs in a Finnish natural gas pipeline. This investigation has lead to several important results in which higher resolution yielded: (1) more realistic amplitudes and timings of GICs, (2) higher amplitude geomagnetic disturbances across latitudes, and (3) increased regional variations in terms of differences between stations. Despite this, substorms remain a significant challenge to surface magnetic field prediction from global magnetohydrodynamic modeling. For example, in the presence of multiple large substorms, the associated large-amplitude depressions were not captured, which caused the largest model-data deviations. The results from this work are of key importance to both modelers and space weather operators. Particularly when the goal is to obtain improved regional forecasts of geomagnetic disturbances and/or more realistic estimates of the geoelectric field.
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| 5. |
- Lanabere, Vanina, et al.
(författare)
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Analysis of the Geoelectric Field in Sweden Over Solar Cycles 23 and 24 : Spatial and Temporal Variability During Strong GIC Events
- 2023
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Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 21:12
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Tidskriftsartikel (refereegranskat)abstract
- Geomagnetic storms can produce large perturbations on the Earth magnetic field. Through complex magnetosphere-ionosphere coupling, the geoelectric field (E) and geomagnetic field (B) are highly perturbed. The E is the physical driver of geomagnetically induced currents. However, a statistical study of the E in Sweden has never been done before. We combined geomagnetic data from the International Monitor for Auroral Geomagnetic Effects network in Northern Europe with a 3-D structure of Earth's electrical conductivity in Sweden as the input of a 1-D model to compute the E between 2000 and 2018. Northwestern Sweden presents statistically larger E magnitudes due to larger |dB/dt| variations in the north than in the south of Sweden and relative lower conductivity in the west compared to central and eastern Sweden. In contrast, the 15 strongest daily maximum |E| events present more frequently a maximum magnitude in central Sweden (62.25 degrees N) and their relative strengths are not the same for all latitudes. These results highlight the different regional response to geomagnetic storms, which can be related to ground conductivity variability and the complex magnetosphere-ionosphere coupling mechanisms. Solar storms represent a major threat to Earth's technology and therefore affect society and the economy. Historically, the main effects were related to electric power grid failures leaving many people without electricity for several hours. In order to prevent this from happening again, it is necessary to understand the temporal and spatial variability of the Earth's electric field in regions where electric power grids are placed. This study combines ground measurements of the magnetic fields in Finland and Estonia and ground conductivity maps in Sweden to estimate the ground electric fields in Sweden. A statistical analysis from 2000 to 2018 shows that the probability to find stronger daily maximum electric field magnitude (|E|) is higher in northwestern Sweden. However, the 15 strongest |E| events were found in the central region of Sweden. Furthermore, 80% of the electric power grid failure reports in Sweden during the period, correspond to events where the strongest daily maximum |E| were observed at 62.25 degrees N. This implies that a better understanding of the local geoelectric field and driving processes are required. The daily maximum geoelectric field magnitude is statistically larger in northwestern Sweden than in central and southern SwedenThe 15 strongest daily maximum geoelectric field events were more frequent in central Sweden than in northern SwedenThe 15 strongest events at each latitude are different, so the geoelectric field presents an important regional variability
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| 6. |
- Lonnblom, E, et al.
(författare)
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AUTOANTIBODIES TO JOINT PROTEINS AS NOVEL BIOMARKERS FOR THE DIAGNOSIS OF UNTREATED EARLY RHEUMATOID ARTHRITIS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 546-546
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Autoantibodies to citrullinated protein (ACPA; measured as anti-CCP; aCCP) and rheumatoid factor (RF) appear years before clinical onset of RA and are essential tools in today’s classification criteria for RA. In animal models, antibodies to joint specific proteins (JP) can induce arthritis, and they are also present at onset of RA [1]. As there is a need for increased precision for early diagnosis of RA as well as identification of different subtypes of the disease, we aim to assess whether autoantibodies to native or modified JP can be used for early and precise diagnosis of RA.ObjectivesTo study whether antibodies to JP, alone or in combination with ACPA/RF, could increase the diagnostic sensitivity and specificity in untreated early (ue)RA patients.MethodsAntibodies to JP were analysed in serum from patients in three independent ueRA cohorts as well as from population controls without rheumatic diseases (WINGA, Gothenburg and MFM-ÅUS, Malmö n=1062). ERAp (n=66), the smallest and most recent cohort was chosen for screening, and BARFOT and TIRA-2 (n=1939) for validation. We have developed a bead-based multianalyte flow immunoassay [2] and screened approx. 350 peptides derived from JPs of interest. We included monoclonal antibodies as assay calibrators and determined limit of detection (LoD). To assess positivity for autoantibodies to JP of interest above LoD, we used 5MAD (median absolute deviation) of the control populations as the cut-off.ResultsIn the ERAp cohort, 5 autoantibodies discriminated RA patients from controls with 81% sensitivity and 100% specificity (Table 1). The same autoantibodies had 68% sensitivity and 98% specificity in the combined BARFOT and TIRA-2 cohorts. Together with RF and aCCP, only 2 of the 5 autoantibodies added statistically significant diagnostic value, increasing the sensitivity from 48% to 61% with 99% specificity. In aCCP- and RF-negative ueRA patients (n=536), the novel biomarkers identified 22.5% of the patients with 99% specificity compared to controls.Table 1.Diagnostic capacity of the joint-specific antibodiesTest panelPerformanceGroup of patientsaCCP+RF+JP+SensitivitySpecificityAUC(ROC)ERApAll patients (n=66)--X81%100%89%RF and aCCP-neg patients (n=7)1------BARFOT and TIRA-2, combined dataAll patients (N=1939)--X68%98%86%All patients (N=1939)X--58%99%78%All patients (N=1939)2XX-48%100%84%All patients (N=1939)2, 3XXX61%99%86%RF and/or aCCP-pos patients (N=1403)--X84%99%93%RF and aCCP-neg patients (N=536)--X22%99%67%RA, literature valuesAnti-CCP testXN/AN/A53–71%95–96%N/A1Not analysed due to lack of power2This patient population is both aCCP+ and RF+3Only 2 of the 5 autoantibodies added statistically significant to the diagnostic valueAUC, Area under the curve; ROC, receiver operating characteristic curve; N/A, not applicable. Controls without rheumatic diseases: N=935 for BARFOT / TIRA-2 and N=27 for ERAp.ConclusionAutoantibodies to JP discriminate ueRA patients better then aCCP and RF alone and add an increased diagnostic value in particular for seronegative patients.References[1]Holmdahl, R., V. Malmstrom, and H. Burkhardt, Autoimmune priming, tissue attack and chronic inflammation - the three stages of rheumatoid arthritis. Eur J Immunol, 2014. 44(6): p. 1593-9.[2]Viljanen, J., et al., Synthesis of an Array of Triple-Helical Peptides from Type II Collagen for Multiplex Analysis of Autoantibodies in Rheumatoid Arthritis. ACS Chem Biol, 2020. 15(9): p. 2605-2615. Correction: ACS Chem Biol, 2020. 15(11): p. 3072AcknowledgementsBARFOT study group.Disclosure of InterestsErik Lönnblom: None declared, Monica Leu Agelii: None declared, Outi Sareila Employee of: Part time employee in Vacara AB, Ingiäld Hafström: None declared, Maria Andersson: None declared, Lei Cheng: None declared, Göran Bergström: None declared, Anna-Karin H Ekwall: None declared, Anna Rudin: None declared, Alf Kastbom: None declared, Christopher Sjowall: None declared, Bingze Xu: None declared, Lennart T.H. Jacobsson: None declared, Johan Viljanen: None declared, Jan Kihlberg: None declared, Inger Gjertsson: None declared, Rikard Holmdahl Shareholder of: Rikard Holmdahl the founder of Vacara AB.
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| 7. |
- Nygård, K., et al.
(författare)
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ForMAX – a beamline for multiscale and multimodal structural characterization of hierarchical materials
- 2024
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Ingår i: Journal of Synchrotron Radiation. - : International Union of Crystallography (IUCr). - 0909-0495 .- 1600-5775. ; 31:Pt 2, s. 363-377
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Tidskriftsartikel (refereegranskat)abstract
- The ForMAX beamline at the MAX IV Laboratory provides multiscale and multimodal structural characterization of hierarchical materials in the nanometre to millimetre range by combining small- and wide-angle X-ray scattering with full-field microtomography. The modular design of the beamline is optimized for easy switching between different experimental modalities. The beamline has a special focus on the development of novel fibrous materials from forest resources, but it is also well suited for studies within, for example, food science and biomedical research.
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| 8. |
- Dimmock, Andrew P., et al.
(författare)
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On the Regional Variability ofdB/dtand Its Significance to GIC
- 2020
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Ingår i: Space Weather. - : AMER GEOPHYSICAL UNION. - 1542-7390. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- Faraday's law of induction is responsible for setting up a geoelectric field due to the variations in the geomagnetic field caused by ionospheric currents. This drives geomagnetically induced currents (GICs) which flow in large ground-based technological infrastructure such as high-voltage power lines. The geoelectric field is often a localized phenomenon exhibiting significant variations over spatial scales of only hundreds of kilometers. This is due to the complex spatiotemporal behavior of electrical currents flowing in the ionosphere and/or large gradients in the ground conductivity due to highly structured local geological properties. Over some regions, and during large storms, both of these effects become significant. In this study, we quantify the regional variability ofdB/dtusing closely placed IMAGE stations in northern Fennoscandia. The dependency between regional variability, solar wind conditions, and geomagnetic indices are also investigated. Finally, we assess the significance of spatial geomagnetic variations to modeling GICs across a transmission line. Key results from this study are as follows: (1) Regional geomagnetic disturbances are important in modeling GIC during strong storms; (2)dB/dtcan vary by several times up to a factor of three compared to the spatial average; (3)dB/dtand its regional variation is coupled to the energy deposited into the magnetosphere; and (4) regional variability can be more accurately captured and predicted from a local index as opposed to a global one. These results demonstrate the need for denser magnetometer networks at high latitudes where transmission lines extending hundreds of kilometers are present.
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| 9. |
- Urbonaviciute, Vilma, et al.
(författare)
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Therapy targeting antigen-specific T cells by a peptide-based tolerizing vaccine against autoimmune arthritis
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Stockholm : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:25
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Tidskriftsartikel (refereegranskat)abstract
- A longstanding goal has been to find an antigen-specific preventive therapy, i.e., a vaccine, for autoimmune diseases. It has been difficult to find safe ways to steer the targeting of natural regulatory antigen. Here, we show that the administration of exog-enous mouse major histocompatibility complex class II protein bounding a unique galactosylated collagen type II (COL2) peptide (Aq-galCOL2) directly interacts with the antigen-specific TCR through a positively charged tag. This leads to expanding a VISTA-positive nonconventional regulatory T cells, resulting in a potent dominant suppressive effect and protection against arthritis in mice. The therapeutic effect is dom-inant and tissue specific as the suppression can be transferred with regulatory T cells, which downregulate various autoimmune arthritis models including antibody-induced arthritis. Thus, the tolerogenic approach described here may be a promising dominant antigen-specific therapy for rheumatoid arthritis, and in principle, for autoimmune diseases in general.
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