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- Galindo-Feria, Angeles S., et al.
(author)
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Proinflammatory Histidyl-Transfer RNA Synthetase-Specific CD4+T Cells in the Blood and Lungs of Patients With Idiopathic Inflammatory Myopathies
- 2020
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In: Arthritis & Rheumatology. - : WILEY. - 2326-5191 .- 2326-5205. ; 72:1, s. 179-191
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Journal article (peer-reviewed)abstract
- Objective Autoantibodies targeting histidyl-transfer RNA synthetase (HisRS; anti-Jo-1) are common in the idiopathic inflammatory myopathies (IIMs) and antisynthetase syndrome. This study was undertaken to investigate immunity against HisRS in the blood and lungs of patients with IIM/antisynthetase syndrome. Methods Bronchoalveolar lavage (BAL) fluid, BAL fluid cells, and peripheral blood mononuclear cells (PBMCs) from patients with IIM/antisynthetase syndrome (n = 24) were stimulated with full-length HisRS protein or a HisRS-derived peptide (HisRS(11-23)). BAL fluid and PBMCs from patients with sarcoidosis (n = 7) and healthy subjects (n = 12) were included as controls. The CD4+ T cell response was determined according to levels of CD40L up-regulation and cytokine expression using flow cytometry. Anti-Jo-1 autoantibody responses in the serum and BAL fluid were assessed by enzyme-linked immunosorbent assay. Lung biopsy samples from patients with IIM/antisynthetase syndrome (n = 14) were investigated by immunohistochemistry. Results In BAL fluid, CD4+ T cells from 3 of 4 patients with IIM/antisynthetase syndrome responded to stimulation with HisRS protein, as measured by the median fold change in CD40L expresssion in stimulated cells compared to unstimulated cells (median fold change 3.6, interquartile range [IQR] 2.7-14.7), and 2 of 3 patients with IIM/antisynthetase syndrome had the highest responses to HisRS(11-23) (median fold change 88, IQR 27-149)(.) In PBMCs, CD4+ T cells from 14 of 18 patients with IIM/antisynthetase syndrome responded to HisRS protein (median fold change 7.38, IQR 2.69-31.86; P < 0.001), whereas a HisRS(11-23) response was present in 11 of 14 patients with IIM/antisynthetase syndrome (median fold change 3.4, IQR 1.87-10.9; P < 0.001). In the control group, there was a HisRS(11-23) response in 3 of 7 patients with sarcoidosis (median fold change 2.09, IQR 1.45-3.29) and in 5 of 12 healthy controls (median fold change 2, IQR 1.89-2.42). CD4+ T cells from patients with IIM/antisynthetase syndrome displayed a pronounced Th1 phenotype in the BAL fluid when compared to the PBMCs (P < 0.001), producing high amounts of interferon-gamma and interleukin-2 following stimulation. Anti-Jo-1 autoantibodies were detected in BAL fluid and germinal center (GC)-like structures were seen in the lung biopsy samples from patients with IIM/antisynthetase syndrome. Conclusion The results of this study demonstrate a pronounced presence of HisRS-reactive CD4+ T cells in PBMCs and BAL fluid cells from patients with IIM/antisynthetase syndrome as compared to patients with sarcoidosis and healthy controls. These findings, combined with the presence of anti-Jo-1 autoantibodies in BAL fluid and GC-like structures in the lungs, suggest that immune activation against HisRS might take place within the lungs of patients with IIM/antisynthetase syndrome.
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- Hansson, Monika, et al.
(author)
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Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides
- 2012
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In: ARTHRITIS RESEARCH & THERAPY. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 14:5, s. R201-
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Journal article (peer-reviewed)abstract
- Introduction: Autoantibodies directed against citrullinated proteins/peptides (ACPAs) are highly specific and predictive for the development of rheumatoid arthritis (RA). Different subgroups of RA patients, which have different prognoses and may require different treatments, are characterized by different autoantibody profiles. The objective of this study was to develop a microarray for the detection of multiple RA-associated autoantibodies, initially focusing on responses against citrullinated epitopes on candidate autoantigens in RA. Methods: The microarray is based on Phadia's ImmunoCAP ISAC system, with which reactivity to more than 100 antigens can be analyzed simultaneously, by using minute serum volumes (<10 mu l). Twelve citrullinated peptides, and the corresponding native arginine-containing control peptides, were immobilized in an arrayed fashion onto a chemically modified glass slide, allowing a three-dimensional layer with high binding capacity. The assay was optimized concerning serum dilution and glass surface, whereas each individual antigen was optimized concerning coupling chemistry, antigen concentration, and selection of spotting buffer. The performance of each peptide in the ImmunoCAP ISAC system was compared with the performance in enzyme-linked immunosorbent assays (ELISAs). Serum from 927 RA patients and 461 healthy controls from a matched case-control study were applied onto reaction sites on glass slides, followed by fluorescent-labeled anti-human immunoglobulin G (IgG) antibody. Fluorescence intensities were detected with a laser scanner, and the results analyzed by using image-analysis software. Results: Strong correlations between the ImmunoCAP ISAC system and ELISA results were found for individual citrullinated peptides (Spearman rho typically between 0.75 and 0.90). Reactivity of RA sera with the peptides was seen mainly in the anticyclic citrullinated peptide 2 (CCP2)-positive subset, but some additional reactivity with single citrullinated peptides was seen in the anti-CCP2-negative subset. Adjusting for reactivity against arginine-containing control peptides did not uniformly change the diagnostic performance for antibodies against the individual citrullinated peptides. Conclusions: The multiplexed array, for detection of autoantibodies against multiple citrullinated epitopes on candidate RA autoantigens, will be of benefit in studies of RA pathogenesis, diagnosis, and potentially as a guide to individualized treatment.
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- Jonsson, B. Lars G., et al.
(author)
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On Spatial Visualization of Mutual Coupling With Applications to Small Embedded Antennas
- 2022
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In: 2022 16TH EUROPEAN CONFERENCE ON ANTENNAS AND PROPAGATION (EUCAP). - : Institute of Electrical and Electronics Engineers (IEEE).
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Conference paper (peer-reviewed)abstract
- Mutual coupling between antennas is a key parameter in multi-antenna systems. The present paper describes a method to map contributions to the magnitude of the mutual coupling spatially on surfaces between the ports. The method utilizes the reaction theorem for electromagnetic fields to obtain the contribution of the coupling from different regions. The derived result is valid for and applied to the strong-coupling regime, where the mutual impedance is of the same order as the self-impedance.
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- Teleman, Johan, et al.
(author)
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Numerical compression schemes for proteomics mass spectrometry data.
- 2014
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In: Molecular & Cellular Proteomics. - 1535-9484. ; 13:6, s. 1537-1542
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Journal article (peer-reviewed)abstract
- The open XML format mzML, used for representation of mass spectrometry (MS) data, is pivotal for the development of platform-independent MS analysis software. Although conversion from vendor formats to mzML must take place on a platform on which the vendor libraries are available (i.e. Windows), once mzML files have been generated, they can be used on any platform. However, the mzML format has turned out to be less efficient than vendor formats. In many cases, the naive mzML representation is 4-fold or even up to 18-fold larger compared to the original vendor file. In disk I/O limited setups, a larger data file also leads to longer processing times, which is a problem given the data production rates of modern mass spectrometers. In an attempt to reduce this problem, we here present a family of numerical compression algorithms called MS-Numpress, intended for efficient compression of MS data. To facilitate ease of adoption, the algorithms target the binary data in the mzML standard, and support in main proteomics tools is already available. Using a test set of 10 representative MS data files we demonstrate typical file size decreases of 90% when combined with traditional compression, as well as read time decreases of up to 50%. It is envisaged that these improvements will be beneficial for data handling within the MS community.
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- Ayebe, Mustafa, 1997, et al.
(author)
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Systematic Self-Interference Mitigation in Full Duplex Antenna Arrays Via Transmit Beamforming
- 2023
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In: 2023 International Conference on Electromagnetics in Advanced Applications, ICEAA 2023. ; , s. 158-163
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Conference paper (peer-reviewed)abstract
- The optimal antenna array excitation vector is derived that maximizes the (realized) array gain in a particular direction while preventing the coupled input power to the low-noise amplifiers on the receive side to exceed a certain maximum threshold level. This is very useful for in-band full-duplex systems where the hardware complexity for self-interference cancellation must be minimized. In this approach, the perfect nulling of interference on the RX side is not required, sparing degrees of freedom for the TX beamformer. We evaluate the performance of the proposed TX beamforming algorithm by showing numerical results of the 25 x-polarized TX and 25 RX with 0.5λ element spacing and λ gap distance between the TX and RX sub-array.
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- Carlsson, Michael, et al.
(author)
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Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins
- 2012
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In: Journal of Clinical Immunology. - : Springer Verlag (Germany). - 0271-9142 .- 1573-2592. ; 32:2, s. 246-255
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Journal article (peer-reviewed)abstract
- Background Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc alpha 2-3Gal). less thanbrgreater than less thanbrgreater thanPurpose The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of beta-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. less thanbrgreater than less thanbrgreater thanMethods Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. less thanbrgreater than less thanbrgreater thanResults Analysis of similar to 100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to similar to 100 controls, consistent with the known loss of galactosylation. A subgroup of similar to 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA andlt;0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. less thanbrgreater than less thanbrgreater thanConclusion This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.
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- Fisher, Jane, et al.
(author)
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Proteome profiling of recombinant DNase therapy in reducing NETs and aiding recovery in COVID-19 patients
- 2021
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In: Molecular and Cellular Proteomics. - : Elsevier BV. - 1535-9484 .- 1535-9476. ; 20
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Journal article (peer-reviewed)abstract
- Severe COVID-19 can result in pneumonia and acute respiratory failure. Accumulation of mucus in the airways is a hall mark of the disease and can result in hypoxemia. Here, we show that quantitative proteome analysis of the sputum from severe COVID-19 patients reveal high levels of neutrophil extracellular trap(s) (NETs) components, which was confirmed by microscopy. Extracellular DNA from excessive NET formation can increase sputum viscosity and can lead to acute respiratory distress syndrome (ARDS). Recombinant human DNase (rhDNase/Pulmozyme) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated 5 COVID-19 patients presenting acute symptoms with clinically approved aerosolized Pulmozyme. No adverse reactions to the drug were seen, and improved oxygen saturation and recovery in all severely ill COVID-19 patients was observed after therapy. Immunofluorescence and proteome analysis of sputum and blood plasma samples after treatment revealed a marked reduction of NETs and a set of statistically significant proteome changes that indicate reduction of haemorrhage, plasma leakage and inflammation in the airways, and reduced systemic inflammatory state in the blood plasma of patients. Taken together, the results indicate that NETs contribute to acute respiratory failure in COVID-19 and that degrading NETs may reduce dependency on external high flow oxygen therapy in patients. Targeting NETs using rhDNase may have significant therapeutic implications in COVID-19 disease and warrants further studies.
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