| 1. |
- Assenhöj, Maria, et al.
(författare)
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Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles–an interdisciplinary approach
- 2021
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Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:8, s. 1035-1038
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Tidskriftsartikel (refereegranskat)abstract
- Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle–protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both ‘danger signals’, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations. © 2021 The Author(s).
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| 2. |
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| 3. |
- Delsing, Louise, et al.
(författare)
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Barrier properties and transcriptome expression in human iPSC-derived models of the blood-brain barrier
- 2018
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Ingår i: Stem Cells. - : AlphaMed Press, Inc.. - 1066-5099 .- 1549-4918. ; 36:12, s. 1816-1827
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Tidskriftsartikel (refereegranskat)abstract
- Cell-based models of the blood-brain barrier (BBB) are important for increasing the knowledge of BBB formation, degradation and brain exposure of drug substances. Human models are preferred over animal models because of inter-species differences in BBB structure and function. However, access to human primary BBB tissue is limited and has shown degeneration of BBB functions in vitro. Human induced pluripotent stem cells (iPSCs) can be used to generate relevant cell types to model the BBB with human tissue. We generated a human iPSC-derived model of the BBB that includes endothelial cells in co-culture with pericytes, astrocytes and neurons. Evaluation of barrier properties showed that the endothelial cells in our co-culture model have high transendothelial electrical resistance, functional efflux and ability to discriminate between CNS permeable and non-permeable substances. Whole genome expression profiling revealed transcriptional changes that occur in co-culture, including upregulation of tight junction proteins such as claudins and neurotransmitter transporters. Pathway analysis implicated changes in the WNT, TNF and PI3K-Akt pathways upon co-culture. Our data suggests that co-culture of iPSC-derived endothelial cells promotes barrier formation on a functional and transcriptional level. The information about gene expression changes in co-culture can be used to further improve iPSC-derived BBB models through selective pathway manipulation.
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| 4. |
- Feldhahn, Magdalena, et al.
(författare)
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miHA-Match : Computational detection of tissue-specific minor histocompatibility antigens
- 2012
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier. - 0022-1759 .- 1872-7905. ; 386:1-2, s. 94-100
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Tidskriftsartikel (refereegranskat)abstract
- Allogenic stem cell transplantation has shown considerable success in a number of hematological malignancies, in particular in leukemia. The beneficial effect is mediated by donor T cells recognizing patient-specific HLA-binding peptides. These peptides are called minor histocompatibility antigens (miHAs) and are typically caused by single nucleotide polymorphisms. Tissue-specific miHAs have successfully been used in anti-tumor therapy without causing unspecific graft-versus-host reactions. However, only a small number of miHAs have been identified to date, limiting the clinical use.Here we present an immunoinformatics pipeline for the identification of miHAs. The pipeline can be applied to large-scale miHA screening, for example, in the development of diagnostic tests. Another interesting application is the design of personalized miHA-based cancer therapies based on patient-donor pair-specific miHAs detected by this pipeline. The suggested method covers various aspects of genetic variant detection, effects of alternative transcripts, and HLA-peptide binding. A comparison of our computational pipeline and experimentally derived datasets shows excellent agreement and coverage of the computationally predicted miHAs.
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| 5. |
- Havervall, Sebastian, et al.
(författare)
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Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19
- 2022
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 291:1, s. 72-80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts.Methods: We investigated SARS-CoV-2-specific humoral and cellular immune responses more than 8 months post-asymptomatic, mild and severe infection in a cohort of 1884 healthcare workers (HCW) and 51 hospitalized COVID-19 patients. Possible protection against SARS-CoV-2 reinfection was analyzed by a weekly 3-month polymerase chain reaction (PCR) screening of 252 HCW that had seroconverted 7 months prior to start of screening and 48 HCW that had remained seronegative at multiple time points.Results: All COVID-19 patients and 96% (355/370) of HCW who were anti-spike IgG positive at inclusion remained anti-spike IgG positive at the 8-month follow-up. Circulating SARS-CoV-2-specific memory T cell responses were detected in 88% (45/51) of COVID-19 patients and in 63% (233/370) of seropositive HCW. The cumulative incidence of PCR-confirmed SARS-CoV-2 infection was 1% (3/252) among anti-spike IgG positive HCW (0.13 cases per 100 weeks at risk) compared to 23% (11/48) among anti-spike IgG negative HCW (2.78 cases per 100 weeks at risk), resulting in a protective effect of 95.2% (95% CI 81.9%-99.1%).Conclusions: The vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.
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| 6. |
- Jensen, Poul Erik H., et al.
(författare)
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Detection and kinetics of persistent neutralizing anti-interferon-beta antibodies in patients with multiple sclerosis : Results from the ABIRISK prospective cohort study
- 2019
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 326, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- Two validated assays, a bridging ELISA and a luciferase-based bioassay, were compared for detection of anti-drug antibodies (ADA) against interferon-beta (IFN-β) in patients with multiple sclerosis. Serum samples were tested from patients enrolled in a prospective study of 18 months. In contrast to the ELISA, when IFN-β-specific rabbit polyclonal and human monoclonal antibodies were tested, the bioassay was the more sensitive to detect IFN-β ADA in patients' sera. For clinical samples, selection of method of ELISA should be evaluated prior to the use of a multi-tiered approach. A titer threshold value is reported that may be used as a predictor for persistently positive neutralizing ADA.
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| 7. |
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| 8. |
- Neiman, Maja, et al.
(författare)
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Plasma Profiling Reveals Human Fibulin-1 as Candidate Marker for Renal Impairment
- 2011
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 10:11, s. 4925-4934
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for reliable and sensitive biomarkers for renal impairments to detect early signs of kidney toxicity and to monitor progression of disease. Here, antibody suspension bead arrays were applied to profile plasma samples from patients with four types of kidney disorders: glomerulonephritis, diabetic nephropathy, obstructive uropathy, and analgesic abuse. In total, 200 clinical renal-associated cases and control plasma samples from different cohorts were profiled. Parallel plasma protein profiles were obtained using biotinylated and nonfractionated samples and a selected set of 94 proteins targeted by 129 antigen-purified polyclonal antibodies. Out of the analyzed target proteins, human fibulin-1 was detected at significantly higher levels in the glomerulonephritis patient group compared to the controls and with elevated levels in patient samples for all other renal disorders investigated. Two polyclonal antibodies and one monoclonal antibody directed toward separate, nonoverlapping epitopes showed the same trend in the discovery cohorts. A technical verification using Western blot analysis of selected patient plasma confirmed the trends toward higher abundance of the target protein in disease samples. Furthermore, a verification study was carried out in the context of glomerulonephritis using an independent case and control cohort, and this confirmed the results from the discovery cohort, suggesting that plasma levels of fibulin-1 could serve as a potential indicator to monitor kidney malfunction or kidney damage.
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| 9. |
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| 10. |
- Synnergren, Jane, 1967-, et al.
(författare)
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Integration of Biomedical Big Data Requires Efficient Batch Effect Reduction
- 2018
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Ingår i: 10th International Conference on Bioinformatics and Computational Biology (BICOB). - 9781943436118 - 9781510858664 ; , s. 76-82
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Konferensbidrag (refereegranskat)abstract
- Efficiency in dealing with batch effects will be the next frontier in large-scale biological data analysis, particularly when involving the integration of different types of datasets. Large-scale omics techniques have quickly developed during the last decade and huge amounts of data are now generated, which has started to revolutionize the area of medical research. With the increase in the volume of data across the whole spectrum of biology, problems related to data analytics are continuously increasing as analysis and interpretation of these large volumes of molecular data has become a real challenge. Tremendous efforts have been made to obtain data from various molecular levels and the most recent trends show that more and more researchers now are trying to integrate data of various molecular types to inform hypotheses and biological questions. Tightly connected to this work are the batch-related biases that commonly are apparent between different datasets, but these problems are often not tackled. In present study the ComBat algorithm was applied and evaluated on two different data integration problems. Results show that the batch effects present in the integrated datasets efficiently could be removed by applying the ComBat algorithm.
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