| 1. |
- Arkestål, Kurt, et al.
(författare)
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Impaired allergy diagnostics among parasite-infected patients caused by IgE antibodies to the carbohydrate epitope galactose-alpha 1,3-galactose
- 2011
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 127:4, s. 1024-1028
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Tidskriftsartikel (refereegranskat)abstract
- Background: The carbohydrate epitope galactose-alpha 1,3galactose (a-Gal) is abundantly expressed on nonprimate mammalian proteins. We have recently shown that alpha-Gal is responsible for the IgE binding to cat IgA, a newly identified cat allergen (Fel d 5). Objective: We sought to investigate the diagnostic relevance of IgE antibodies to Fel d 5 and a-Gal among parasite-infected patients from central Africa without cat allergy compared with patients with cat allergy from the same region. Methods: Sera from 47 parasite-infected patients and 31 patients with cat allergy were analyzed for total IgE and IgE antibodies against cat dander extract (CDE) by using the ImmunoCAP system. Inhibition assay was performed with a-Gal on solid phase-bound CDE. The presence of IgE specific for the major cat allergen Fel d 1, Fel d 5, and alpha-Gal was analyzed by means of ELISA. Results: Among the 47 parasite-infected patients, 85% had IgE antibodies against alpha-Gal (OD; median, 0.175; range, 0.1021.466) and 66% against Fel d 5 (OD; median, 0.13; range, 0.1031.285). Twenty-four of the parasite-infected patients were sensitized to CDE, and 21 of them had IgE antibodies to Fel d 5 and a-Gal. There was no correlation between IgE levels to CDE and rFel d 1 among the parasite-infected patients but a strong correlation between CDE and Fel d 5 and alpha-Gal (P <. 001). Among the group with cat allergy, only 5 patients had IgE to alpha-Gal, and nearly 75% (n 5 23) had IgE to rFel d 1 (median, 7.07 kU(A)/L; range, 0.51-148.5 kUA/ L). In contrast, among the patients with cat allergy, there was a correlation between IgE levels to CDE and rFel d 1 (P <.05) but no correlation between CDE and Fel d 5 and alpha-Gal. Conclusion: IgE to alpha-Gal causes impaired allergy diagnostics in parasite-infected patients. Screening for IgE to rFel d 1 and other allergens without carbohydrates might identify patients with true cat sensitization/ allergy in parasite-infested areas.
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| 2. |
- Bedri, Sahl Khalid, et al.
(författare)
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Plasma protein profiling reveals candidate biomarkers for multiple sclerosis treatment
- 2019
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) treatment options have improved significantly over the past decades, but the consequences of MS can still be devastating and the needs for monitoring treatment surveillance are considerable. In the current study we used affinity proteomics technology to identify potential biomarkers which could ultimately be used to as facilitate treatment decisions. We profiled the intra-individual changes in the levels of 59 target proteins using an antibody suspension bead array in serial plasma samples from 44 MS patients during treatment with natalizumab followed by fingolimod. Nine proteins showed decreasing plasma levels during natalizumab treatment, with PEBP1 and RTN3 displaying the most significant changes. Protein levels remained stable during fingolimod treatment for both proteins. The decreasing PEBP1 levels during natalizumab treatment could be validated using ELISA and replicated in an independent cohort. These results support the use of this technology as a high throughput method of identifying potentially useful biomarkers of MS treatment.
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| 3. |
- Bengtsson, Magnus, et al.
(författare)
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Lidar fluorescence measurements of algal growth on electrical insulators
- 2003
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Ingår i: 2003 Conference on Lasers and Electro-Optics Europe (CLEO/Europe 2003) (IEEE Cat. No.03TH8666). - 0780377346 ; , s. 473-473
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Konferensbidrag (refereegranskat)abstract
- Fluorescence measurements using lidar techniques have been shown to be useful for monitoring of algal growth on e.g. historical monuments. In this experiment similar measurements were performed on electrical insulators to examine the correlation between algal growth and the quality of the insulator, a factor of importance in the high-voltage grid management
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| 4. |
- Bennett, M, et al.
(författare)
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Joint application of Doppler Lidar and differential absorption lidar to estimate the atomic mercury flux from a chlor-alkali plant
- 2006
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 40:4, s. 664-673
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Tidskriftsartikel (refereegranskat)abstract
- We have combined differential absorption lidar (DIAL) measurements of mercury concentrations downwind of a chloralkali plant (Rosignano Solvay) with measurements of wind profiles made with a Doppler Lidar based on modern fibreoptic technology. Since the flux of pollutant is equal to the cross-wind integral of the product of concentration and wind speed, this should permit us to make a more precise estimate of the fugitive emission of mercury from the plant than could be obtained by using anemometer measurements of the wind. The flux was estimated to be 54g Hgh(-1) using an anemometer on the plant building; 49g Hgh(-1) using an anemometer on a nearby 10m mast; and 48g Hgh(-1) using wind speed corrections estimated from the Doppler Lidar measurements. Because of difficulties with the range resolution of the Doppler Lidar, the precision of this estimate was not as good as it should have been, though the difference from the rooftop anemometer remains statistically significant. Corrections of this magnitude are irrelevant to the Rosignano plant, where the emission rate varies strongly with the meteorological conditions. Where a precise estimate of a steady flux is required, however, reliable measurements of the wind profile in the wake of the source are essential. Doppler Lidar provides a possible method for acquiring such measurements. (c) 2005 Elsevier Ltd. All rights reserved.
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| 5. |
- de Faire, Ulf, et al.
(författare)
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Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men : Effects on uptake of oxidized LDL in macrophages as a potential mechanism
- 2010
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 34:2, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in prediction of cardiovascular disease (CVD) and on macrophage uptake of Oxidized LDL (OxLDL). Methods: From a screening of 4232 subjects, 60-year-old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ischemic stroke, or hospitalized angina pectoris) and 633 age- and sex-matched controls were identified through a 5-7 year follow-up. Serum levels of IgM anti-PC was determined by ELISA. Anti-PC was extracted from pooled human IgM and the effect of anti-PC on the uptake of OxLDL was studied by FACScan. Results: Relative risks (RR) with 95% confidence intervals (Cl) by quartiles of anti-PC levels with quartile 4 set as the reference value (RR = 1.0) and adjusted for smoking, BMI, type 11 diabetes, hypercholesterolaemia, and high blood pressure yielded an excess risk for CVD only for those within the lowest quartile of anti-PC values with an RR of 1.37 (CI 0.87-2.16). However, for men stronger associations were noted with increasing multivariately adjusted RRs from quartile 4 to quartile 1. Subjects within quartile I (values below 29.7 U/ml) had a significantly increased RR of 1.96 (Cl 1.09-3.55). Further adjustments for hsCRP gave essentially the same results. No excess risk was noted for women. Specific anti-PC could be extracted from IgM and these antibodies inhibited macrophage uptake of OxLDL Conclusions: Low IgM anti-PC could be a novel risk marker for CVD among men. One possible mechanism could be inhibition of uptake of oxLDL in macrophages.
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| 6. |
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| 7. |
- Dernfalk, Andreas, 1975, et al.
(författare)
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Laser-induced fluorescence spectroscopy for detection of biological contamination on composite insulators
- 2003
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Ingår i: In Proc. 13th International Symposium on High Voltage Engineering, Delft, Netherlands.
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Konferensbidrag (refereegranskat)abstract
- A new technique for remote detection of biological contamination on high-voltage outdoor insulators has been investigated. The technique, which is based on laser-induced fluorescence (LIF) spectroscopy, has been applied to study surfaces of real silicon rubber insulators from a distance of approximately 60 m. Measurements were performed outdoors on a number of clean, as well as, biologically contaminated insulators. Several types of biological contamination were included, as five of the studied insulators had become covered when installed in Sweden, and another three had been contaminated by fungal growth in laboratory. Fluorescence spectra obtained from the surfaces of the described insulators are presented and the applicability of the technique is discussed and compared with photographic methods.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Grönlund, Hans
(författare)
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Diagnosis of IgE-mediated allergy : new approaches using recombinant allergens
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- More than 10% of the population in industrialized countries suffer from lgE-mediated cat allergy. Allergens produced by recombinant techniques offer new possibilites to diagnose and treat allergic patients but will also help to uncover the mechanisms behind the sensitisation. The aim of this thesis was to investigate the clinical usefulness of a recombinant form of the major cat allergen, Fel d 1, from construction of genes and characterisation to diagnosis of cat allergic patients. Furthermore, tools for treatment were developed using the Fel d 1 structure and the major allergen in timothy, Phl p 5. Although Fel d 1 was cloned more than a decade ago, attempts to produce a tetrameric allergen by recombinant methods with structural features similar to the natural allergen have been only partially successful. A synthetic gene coding for direct fusion of the two chains of Fel d 1 was constructed. Expression resulted in a 30 kDa non-covalently associated homodimer. Biochemical and biological analysis showed that the overall fold and immunological properties were very similar to those of natural Fel d 1. The recombinant (r)Fel d 1 construct was subsequently used to determine the structure by X-ray crystallography at 1.8 A resolution. The fold of Fel d 1 presents a striking resemblance to uteroglobin, a molecule with anti-inflammatory and immunomodulatory properties. An internal pocket and the surface localisation of three previously defined Fel d 1 lgE epitopes is presented. We evaluated the diagnostic usefulness of lgE and IgG4 antibodies to rFel d 1 in children and adults with doctors' diagnosis of rhinoconjunctivitis (RC) andlor asthma due to cat. All patients showed positive lgE responses to rFel d 1 by ELISA. Sera from children displayed higher lgE levels to rFel d 1 compared to the adult patients. There was a close correlation between lgE responses by CAP to rFel d 1 and the cat dander extract" however the lgE levels to the single rFel d 1 molecule were significantly higher. Among children with asthma, the lgE levels to rFel d 1 were higher in comparison to both the asthmatic adults and children with RC, whereas the IgG4 levels were elevated in adults with allergic RC compared to adults with asthma. The only curative treatment of allergic disease is allergy vaccination, however the patients face the risk of side effects. Allergens with decreased lgE-binding capacity, but retained Tcell reactivity (hypoallergens) have been tested in clinical trials. We present a new approach of how to generate hypoallergens using structural information and knowledge of B- and T-cell epitopes. The structure of the model allergen Fel d 1 was systematically altered by duplication of T-cell epitopes and disruption of disulphide bonds. Three derivatives displayed a marked reduction in lgE-binding capacity, induced a lower degree of basophil activation but stimulated T-cell proliferation equally well compared to rFel d 1, and are therefore promising hypoallergen candidates. The occurrence of side effects caused by the aluminium hydroxide adjuvant (Alum) by allergy vaccination is frequently reported. In a mouse model using the recombinant version of the timothy pollen allergen Phl p 5, we demonstrated that carbohydrate-based particles (CBP) exhibit several potential advantages over aluminium-hydroxide as adjuvant for immunotherapy. CBP covalently bound to rPhl p 5b (CBP-p5) induced a strong antibody response, which cross-reacted with group 5 allergens from other grass species and exhibited characteristics of blocking antibodies. Alum-5b induced a preferential allergen-specific Th2 cytokine profile, whereas CBP-p5 induced a mixed Th1/Th2 response. CBP-p5 yielded a stable vaccine formulation with preserved immunogenic features and, in contrast to Alum, induced no granulomatous tissue reactions. In conclusion, the work presented in this thesis presents the development of a clinically relevant allergen, from idea, via biochemical, biological and structural characterization to diagnosis of cat-allergic patients and also the rational design of allergens and development of a novel adjuvant for therapeutic purposes.
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| 13. |
- Grönlund, Hans, et al.
(författare)
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Low levels of IgM antibodies against phosphorylcholine predict development of acute myocardial infarction in a population-based cohort from northern Sweden.
- 2009
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Sage. - 1741-8267 .- 1741-8275. ; 16:3, s. 382-386
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Phosphorylcholine (PC) is one important epitope on oxidized low-density lipoprotein that may play an important role by contributing to the atherogenicity of oxidized low-density lipoprotein. IgM antibodies against PC (anti-PC) are present ubiquitously in the population as natural antibodies. We here determine the association between anti-PC and incidence of myocardial infarction (MI). METHODS: We studied 462 incident cases of first events of MI and 888 age-matched and sex-matched controls identified through 13 years of follow-up (1987-1999) of participants in a population-based study from northern Sweden. Relative risks (RRs) with 95% confidence intervals (CIs) of incident MI with adjustments for age, sex, geographical region, hypertension, diabetes, BMI, smoking habits, s-cholesterol and high-sensitivity C-reactive protein were determined. Anti-PC levels were measured by enzyme-linked immunoassay. RESULTS: Low anti-PC values were associated with increased risk of MI. Significant associations were found for values below 26.8 U/ml, corresponding to the lowest 25th percentile, and the highest association was seen below 16.9 U/ml. These results remained almost the same after adjustment for confounding factors (RR crude: 1.56, CI: 1.07-2.28 and RR adjusted: 1.69, CI: 1.09-2.54). CONCLUSION: Low levels of natural IgM anti-PC could play an important role as risk markers for development of MI. Adjustment for common confounders only marginally affected the RR, suggesting that the addition of IgM anti-PC add independent information to the more traditional risk factors.
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| 14. |
- Grönlund, Rasmus, et al.
(författare)
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Elemental mercury emissions from chlor-alkali plants measured by lidar techniques
- 2005
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 39:39, s. 7474-7480
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Tidskriftsartikel (refereegranskat)abstract
- Differential absorption lidar (DIAL) techniques have been utilized to measure elemental gaseous mercury fluxes from mercury cell chlor-alkali (MCCA) plants as a part of the European Union funded European mercury emissions from chlor-alkali plants (EMECAP) project. Three plants have been selected as study objects and a total of six measurement campaigns have been performed, one intercalibration campaign and five flux evaluation campaigns, in both winter and summer. The measurements were carried out using the Swedish optical parametric oscillator-(OPO) based mobile lidar system developed at Lund Institute of Technology. The study shows large differences in the mercury emissions measured in winter or summer and at the different plants. The average values for the campaigns ranged from 6 g h(-1) in the winter campaign at the Swedish plant to 54 g h(-1) in the summer campaign at the Italian plant.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Grönlund, Rasmus, et al.
(författare)
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Mercury emissions from the Idrija mercury mine measured by differential absorption lidar techniques and a point monitoring absorption spectrometer
- 2005
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 39:22, s. 4067-4074
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Tidskriftsartikel (refereegranskat)abstract
- Mercury emission measurements from the ldrija mercury mine in Slovenia were performed during an early November 2003 campaign, where the differential lidar technique was used to map mercury concentrations and an attempt was made to quantify the total mercury flux from the most contaminated area, the abandoned cinnabar roasting oven complex. Lidar concentration data were compared with data recorded with a Zeeman modulated atomic absorption instrument, operated from a vehicle equipped with a GPS localization system. Concentrations and fluxes were comparatively low due to low temperature and rainfall. The average flux from the distillation plant was measured to approximately 2 g h(-1).
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| 19. |
- Guan, Zuguang, et al.
(författare)
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Gas analysis within remote porous targets using LIDAR multi-scatter techniques
- 2008
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Ingår i: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 93:2-3, s. 657-663
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Tidskriftsartikel (refereegranskat)abstract
- Light detection and ranging (LIDAR) experiments are normally pursued for range resolved atmospheric gas measurements or for analysis of solid target surfaces using fluorescence of laser-induced breakdown spectroscopy. In contrast, we now demonstrate the monitoring of free gas enclosed in pores of materials, subject to impinging laser radiation, employing the photons emerging back to the surface laterally of the injection point after penetrating the medium in heavy multiple scattering processes. The directly reflected light is blocked by a beam stop. The technique presented is a remote version of the newly introduced gas in scattering media absorption spectroscopy (GASMAS) technique, which so far was pursued with the injection optics and the detector in close contact with the sample. Feasibility measurements of LIDAR-GASMAS on oxygen in polystyrene foam were performed at a distance of 6 m. Multiple-scattering induced delays of the order of 50 ns, which corresponds to 15 m optical path length, were observed. First extensions to a range of 60 m are discussed. Remote observation of gas composition anomalies in snow using differential absorption LIDAR (DIAL) may find application in avalanche victim localization or for leak detection in snow-covered natural gas pipelines. Further, the techniques may be even more useful for short-range, non-intrusive GASMAS measurements, e.g., on packed food products.
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| 20. |
- Guan, Zuguang, et al.
(författare)
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LIDAR technique for Remote Gas Analysis in Solid Scattering Media
- 2009
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Ingår i: Asia Optical Fiber Communication & Optoelectronic Exposition & Conference, 2008. AOE 2008.. - 9781557528636
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Konferensbidrag (refereegranskat)abstract
- LIDAR techniques are used to measure gases in solid scattering media remotely, by analyzing the differential absorption observed in the multiple scattering light. The gas exchange (O-2/N-2) in polystyrene foam is monitored. (C)2008 Optical Society of America
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| 21. |
- Högelin, Klara Asplund, et al.
(författare)
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Development of humoral and cellular immunological memory against SARS-CoV-2 despite B cell depleting treatment in multiple sclerosis
- 2021
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 24:9
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Tidskriftsartikel (refereegranskat)abstract
- B cell depleting therapies (BCDTs) are widely used as immunomodulating agents for autoimmune diseases such as multiple sclerosis. Their possible impact on development of immunity to severe acute respiratory syndrome virus-2 (SARS-CoV-2) has raised concerns with the coronavirus disease 2019 (COVID-19) pandemic. We here evaluated the frequency of COVID-19-like symptoms and determined immunological responses in participants of an observational trial comprising several multiple sclerosis disease modulatory drugs (COMBAT-MS; NCT03193866) and in eleven patients after vaccination, with a focus on BCDT. Almost all seropositive and 17.9% of seronegative patients on BCDT, enriched for a history of COVID-19-like symptoms, developed anti-SARS-CoV-2 T cell memory, and T cells displayed functional similarity to controls producing IFN-gamma and TNF. Following vaccination, vaccine-specific humoral memory was impaired, while all patients developed a specific T cell response. These results indicate that BCDTs do not abrogate SARS-CoV-2 cellular memory and provide a possible explanation as to why the majority of patients on BCDTs recover from COVID-19.
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| 22. |
- Käck, Ulrika, et al.
(författare)
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Molecular allergy diagnostics refine characterization of children sensitized to dog dander
- 2018
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 142:4, s. 1113-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sensitization to dog dander is an important risk factor for rhinoconjunctivitis and asthma but is not sufficient for diagnosing dog allergy. Molecular allergy diagnostics offer new opportunities for refined characterization. Objectives: We sought to study the association between sensitization to all presently known dog allergen components and clinical symptoms of dog allergy in children evaluated by using nasal provocation tests (NPTs). Methods: Sixty children (age, 10-18 years) sensitized to dog dander extract underwent NPTs with dog dander extract. Measurement of IgE levels to dog dander and to Can f 1, Can f 2, Can f 3, and Can f 5 was performed with ImmunoCAP, and measurement of IgE levels to Can f 4 and Can f 6 was performed with streptavidin ImmunoCAP. An IgE level of 0.1 kU(A)/L or greater was considered positive. Results: There was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge result (P = .01). Sensitization to lipocalins (odds ratio [OR], 6.0; 95% CI, 1.04-34.5), in particular Can f 4 (OR, 6.80; 95% CI 1.84-25.2) and Can f 6 (OR, 5.69; 95% CI, 1.59-20.8), was associated with a positive NPT result. Monosensitization to Can f 5 was related to a negative NPT result (OR, 5.78; 95% CI, 1.01-33.0). Conclusion: Sensitization to an increasing number of dog allergen components and to lipocalins is associated with dog allergy. Monosensitization to Can f 5 should not be regarded primarily as a marker for dog allergy.
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| 23. |
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| 24. |
- Magalhaes, Isabelle, et al.
(författare)
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Facing the future : challenges and opportunities in adoptive T cell therapy in cancer
- 2019
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Ingår i: Expert Opinion on Biological Therapy. - : Taylor & Francis Group. - 1471-2598 .- 1744-7682. ; 19:8, s. 811-827
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In recent years, immunotherapy for the treatment of solid cancer has emerged as a promising therapeutic alternative. Adoptive cell therapy (ACT), especially T cell-based, has been found to cause tumor regression and even cure in a percentage of treated patients. Checkpoint inhibitors further underscore the potential of the T cell compartment in the treatment of cancer. Not all patients respond to these treatments; however, many challenges remain.AREAS COVERED: This review covers the challenges and progress in tumor antigen target identification and selection, and cell product manufacturing for T cell ACT. Tumor immune escape mechanisms and strategies to overcome those in the context of T cell ACT are also discussed.EXPERT OPINION: The immunotherapy toolbox is rapidly expanding and improving, and the future promises further breakthroughs in the T cell ACT field. The heterogeneity of the tumor microenvironment and the multiplicity of tumor immune escape mechanisms pose formidable challenges to successful T cell immunotherapy in solid tumors, however. Individualized approaches and strategies combining treatments targeting different immunotherapeutic aspects will be needed in order to expand the applicability and improve the response rates in future.
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| 25. |
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| 26. |
- Nilsson, Ola B., et al.
(författare)
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Designing a Multimer Allergen for Diagnosis and Immunotherapy of Dog Allergic Patients
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dog dander extract used for diagnosis and allergen-specific immunotherapy is often of variable and of poor quality.Objective: To assemble four well-established dog allergen components into one recombinant folded protein for improved diagnosis and vaccination of allergy to dog.Methods: A linked molecule, comprising the four dog lipocalin allergens Can f 1, Can f 2, Can f 4 and Can f 6 was constructed. The tetrameric protein was structurally characterized by small angle X-ray scattering, and compared with each single recombinant lipocalin allergen or an equimolar mix of the four allergens by analytical size exclusion chromatography, circular dichroism, allergen-specific IgE in serum by ELISA and allergen-dependent capacity to activate basophils. The immunogenicity of the fusion protein was evaluated in immunized mice by assessing splenocyte proliferation and antibody production.Results: The linked tetrameric construct was produced as a soluble fusion protein, with the specific folds of the four individual allergens conserved. This multi-allergen molecule was significantly more efficient (p < 0.001) than each single recombinant allergen in binding to dog-specific IgE, and the epitope spectrum was unaffected compared to an equimolar mix of the four allergens. Basophil degranulation revealed that the biologic activity of the linked molecule was retained. Immunization of mice with the linked construct induced comparable allergen-specific IgG responses with blocking capacity towards all included allergens and generated comparably low T-cell responses.Conclusion: We provide the first evidence for a linked recombinant molecule covering the major dog allergens for potential use in diagnostics and allergy vaccination of dog allergic patients.
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| 27. |
- Nilsson, Ola B., et al.
(författare)
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In vitro evolution of allergy vaccine candidates, with maintained structure, but reduced B cell and T cell activation capacity
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses. The aim of this study was to produce an allergy vaccine designed with the combined features of attenuated T cell activation, reduced anaphylactic properties, retained molecular integrity and induction of efficient IgE blocking IgG antibodies for safer and efficacious treatment of patients with allergy and asthma to cat. The template gene coding for rFel d 1 was used to introduce random mutations, which was subsequently expressed in large phage libraries. Despite accumulated mutations by up to 7 rounds of iterative error-prone PCR and biopanning, surface topology and structure was essentially maintained using IgE-antibodies from cat allergic patients for phage enrichment. Four candidates were isolated, displaying similar or lower IgE binding, reduced anaphylactic activity as measured by their capacity to induce basophil degranulation and, importantly, a significantly lower T cell reactivity in lymphoproliferative assays compared to the original rFel d 1. In addition, all mutants showed ability to induce blocking antibodies in immunized mice.The approach presented here provides a straightforward procedure to generate a novel type of allergy vaccines for safer and efficacious treatment of allergic patients.
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| 28. |
- Nilsson, Ola B., et al.
(författare)
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Mammalian-derived respiratory allergens - Implications for diagnosis and therapy of individuals allergic to furry animals
- 2014
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Ingår i: Methods. - : Elsevier BV. - 1046-2023 .- 1095-9130. ; 66:1, s. 86-95
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Tidskriftsartikel (refereegranskat)abstract
- Furry animals cause respiratory allergies in a significant proportion of the population. A majority of all mammalian allergens are spread as airborne particles, and several have been detected in environments where furry animals are not normally kept. The repertoire of allergens from each source belongs to a restricted number of allergen families. Classification of allergen families is particularly important for the characterization of allergenicity and cross-reactivity of allergens. In fact, major mammalian allergens are taken from only three protein families, i.e. the secretoglobin, lipocalin and kallikrein families. In particular, the lipocalin superfamily harbours major allergens in all important mammalian allergen sources, and cross-reactivity between lipocalin allergens may explain cross-species sensitization between mammals. The identification of single allergen components is of importance to improve diagnosis and therapy of allergic patients using component-resolved diagnostics and allergen-specific immunotherapy (ASIT) respectively. Major disadvantages with crude allergen extracts for these applications emphasize the benefits of careful characterization of individual allergens. Furthermore, detailed knowledge of the characteristics of an allergen is crucial to formulate attenuated allergy vaccines, e.g. hypoallergens. The diverse repertoires of individual allergens from different mammalian species influence the diagnostic potential and clinical efficacy of ASIT to furry animals. As such, detailed knowledge of individual allergens is essential for adequate clinical evaluation. This review compiles current knowledge of the allergen families of mammalian species, and discusses how this information may be used for improved diagnosis and therapy of individuals allergic to mammals.
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| 29. |
- Sjöberg, Beatrice G., et al.
(författare)
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Low levels of IgM antibodies against phosphorylcholine : a potential risk marker for ischemic stroke in men
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 203:2, s. 528-532
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Natural antibodies specific for phosphorylcholine (anti-PC) have been implicated as protective factors in atherosclerosis. We herein determined the relationship between IgM anti-PC and incidence of cardiovascular disease (CVD). METHODS: We studied 349 incident cases (200 men) of first events of CVD (coronary heart disease (CHD; n=203 or ischemic stroke; n=146) and 693 age- and sex-matched controls identified through 12 years of follow-up (1991-2003) of subjects from the cardiovascular cohort within the Malmö Diet and Cancer Study. Relative risks (RR) of CVD with 95% confidence intervals (CI) of incident CVD with adjustments for age, smoking, total cholesterol and blood pressure were determined. Anti-PC-levels were measured using ELISA (Athera CVDefine). RESULTS: As determined using Athera CVDefine, significant associations were attained with values of anti-PC below 17U/ml (corresponding to the lowest 9th percentile), which remained after taking confounders into account (RR: 1.79, 95% CI: 1.09-2.94, p=0.021). If men were studied separately, significance was evident at values below 17U/ml (RR: 2.01, 95% CI: 1.11-3.67, p=0.022), which was not the case among women. Furthermore, values below 17U/ml were also associated with ischemic stroke (RR=3.67, 95% CI: 1.34-10.1, p=0.01), but not with CHD. CONCLUSION: Low IgM anti-PC could be a novel risk marker for development of ischemic stroke in men. Further studies are needed to establish gender and subgroup differences.
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| 30. |
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| 31. |
- Thomas, Olivia G., et al.
(författare)
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Cross-reactive EBNA1 immunity targets alpha-crystallin B and is associated with multiple sclerosis
- 2023
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 9:20
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, for which and Epstein-Barr virus (EBV) infection is a likely prerequisite. Due to the homology between Epstein-Barr nuclear antigen 1 (EBNA1) and alpha-crystallin B (CRYAB), we examined antibody reactivity to EBNA1 and CRYAB peptide libraries in 713 persons with MS (pwMS) and 722 matched controls (Con). Antibody response to CRYAB amino acids 7 to 16 was associated with MS (OR = 2.0), and combination of high EBNA1 responses with CRYAB positivity markedly in-creased disease risk (OR = 9.0). Blocking experiments revealed antibody cross-reactivity between the homolo-gous EBNA1 and CRYAB epitopes. Evidence for T cell cross-reactivity was obtained in mice between EBNA1 and CRYAB, and increased CRYAB and EBNA1 CD4+ T cell responses were detected in natalizumab-treated pwMS. This study provides evidence for antibody cross-reactivity between EBNA1 and CRYAB and points to a similar cross-reactivity in T cells, further demonstrating the role of EBV adaptive immune responses in MS development.
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- Österlund, Camilla, 1978-, et al.
(författare)
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Non-proteolytic aeroallergens from mites, cat and dog exert adjuvant-like activation of bronchial epithelial cells
- 2011
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 155:2, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to seasonal or indoor allergens may cause sensitisation and development of allergic airway diseases. We have previously demonstrated that the non-proteolytic major house dust mite (HDM) allergen Der p 2 stimulates pro-inflammatory responses in bronchial epithelial cells. We aimed to determine if other clinically relevant non-proteolytic aeroallergens originating from HDMs, storage mites, cat, dog, birch and timothy also activate respiratory epithelial cells. Methods: Cultures of human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial cells and alveolar epithelial cell line A549 were exposed to recombinant (r)Der p 2, natural (n)Der f 2, rEur m 2, rLep d 2, rFel d 1, nFel d 1, rCan f 2, rBet v 1 or rPhl p 5a. A panel of secreted mediators and expression of cell adhesion receptors involved in recruitment, survival and adhesion of inflammatory cells in asthmatic airways was assessed. Results: The mite allergens rDer p 2, nDer f 2, rEur m 2 and rLep d 2 as well as the cat and dog allergens rFel d 1, nFel d 1 and rCan f 2 induced granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3α secretion from bronchial epithelial cells as well as surface expression of intracellular adhesion molecule-1. The pollen allergens rBet v 1 and rPhl p 5a from birch and timothy did not activate the cells. None of the studied allergens affected the alveolar epithelial cells. Conclusion: These results show that both mite and structurally unrelated cat and dog allergens can activate respiratory epithelial cells by adjuvant-like protease-independent mechanisms.
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