| 1. |
|
|
| 2. |
- Asarnoj, A., et al.
(författare)
-
IgE to peanut allergen components : relation to peanut symptoms and pollen sensitization in 8-year-olds
- 2010
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 65:9, s. 1189-1195
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Allergen-specific IgE testing is often performed with crude peanut extract, but the results may be difficult to interpret because of cross-reactions between peanut and other plant allergens. The aim was to investigate IgE reactivity to peanut allergen components in children from a birch-rich region in relation to pollen sensitization and peanut symptoms. Methods: From a birth cohort, clinical parameters were obtained through questionnaires and IgE antibody levels to peanut and birch pollen were measured. Different peanut/birch sensitization phenotypes were defined among 200 selected children. IgE reactivity to peanut and pollen allergen components was analysed using microarray technique. Results: Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 (n = 46) vs 17% of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 (n = 23), P < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3 reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more often reported peanut symptoms than children with IgE only to Ara h 2 (97% vs 70%, P = 0.016), particularly respiratory symptoms (50% vs 9%, P = 0.002). Conclusions: IgE analysis to peanut allergen components may be used to distinguish between peanut-sensitized individuals at risk of severe symptoms and those likely to have milder or no symptoms to peanut if sensitized to pollen allergens and their peanut homologue allergens.
|
|
| 3. |
- Azeez, Ahmed, 1991-, et al.
(författare)
-
Out-of-phase thermomechanical fatigue crack propagation in a steam turbine steel — modelling of crack closure
- 2021
-
Ingår i: International Journal of Fatigue. - : Elsevier. - 0142-1123 .- 1879-3452. ; 149
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding of crack growth behaviour is necessary to predict accurate fatigue lives. Out-of-phase thermomechanical fatigue crack propagation tests were performed on FB2 steel used in high-temperature steam turbine sections. Testing results showed crack closure where the compressive part of the fatigue cycle affected crack growth rate. Crack closing stress was observed to be different, and had more influence on the growth rate, than crack opening stress. Crack growth rate was largely controlled by the minimum temperature of the cycle, which agreed with an isothermal crack propagation test. Finite element models with stationary sharp cracks captured the crack closure behaviour.
|
|
| 4. |
- Azeez, Ahmed, 1991-, et al.
(författare)
-
The effect of dwell times and minimum temperature on out-of-phase thermomechanical fatigue crack propagation in a steam turbine steel - Crack closure prediction
- 2022
-
Ingår i: International Journal of Fatigue. - : Elsevier Science Ltd. - 0142-1123 .- 1879-3452. ; 162
-
Tidskriftsartikel (refereegranskat)abstract
- Exploring crack growth behaviour is needed to establish accurate fatigue life predictions. Cracked specimens were tested under strain-controlled out-of-phase thermomechanical fatigue conditions. The tests included dwell times and three different minimum temperatures. Higher minimum temperature gave faster crack growth rates while the additions of dwell times showed no effects. Crack closure was observed in all the tests where the addition of dwell times and change in minimum temperature displayed little to no effect on crack closure stresses. Finite element models with a sharp stationary crack and material parameters switching provided acceptable predictions for the maximum, minimum, and crack closure stresses.
|
|
| 5. |
- Balachandramurthi, Arun Ramanathan, 1989-, et al.
(författare)
-
Anisotropic fatigue properties of Alloy 718 manufactured by Electron Beam Powder Bed Fusion
- 2020
-
Ingår i: International Journal of Fatigue. - : Elsevier. - 0142-1123 .- 1879-3452. ; 141
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, Alloy 718 specimens manufactured by Electron Beam Powder Bed Fusion process are subjected to two different post-treatments to have different microstructural features. Low cycle fatigue testing has been performed both parallel and transverse to the build direction. EB-PBF Alloy 718 exhibits anisotropic fatigue behaviour; the fatigue life is better along the parallel direction compared to the transverse direction. The anisotropy in fatigue life is related to the anisotropy in the Young’s modulus. The pseudo-elastic stress vs. fatigue life approach is presented as a potential solution to handle anisotropy in fatigue life assessment of additively manufactured engineering components. © 2020 The Authors
|
|
| 6. |
- Balachandramurthi, Arun Ramanathan
(författare)
-
Fatigue Properties of Additively Manufactured Alloy 718
- 2018
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Additive Manufacturing (AM), commonly known as 3D Printing, is a disruptive modern manufacturing process, in which parts are manufactured in a layer-wise fashion. Among the metal AM processes, Powder Bed Fusion (PBF) technology has opened up a design space that was not formerly accessible with conventional manufacturing processes. It is, now, possible to manufacture complex geometries, such as topology-optimized structures, lattice structures and intricate internal channels, with relative ease. PBF is comprised of Electron Beam Melting (EBM) and Selective Laser Melting (SLM) processes.Though AM processes offer several advantages, the suitability of these processes to replace conventional manufacturing processes must be studied in detail; for instance, the capability to produce components of consistent quality. Therefore, understanding the relationship between the AM process together with the post treatment used and the resulting microstructure and its influence on the mechanical properties is crucial, to enable manufacturing of high-performance components. In this regard, for AM built Alloy 718, only a limited amount of work has been performed compared to conventional processes such as casting and forging. The aim of this work, therefore, is to understand how the fatigue properties of EBM and SLM built Alloy 718, subjected to different thermal post-treatments, is affected by the microstructure. In addition, the effect of as-built surface roughness is also studied.Defects can have a detrimental effect on fatigue life. Numerous factors such as the defect type, size, shape, location, distribution and nature determine the effect of defects on properties. Hot Isostatic Pressing (HIP) improves fatigue life as it leads to closure of most defects. Presence of oxides in the defects, however, hinders complete closure by HIP. Machining the as-built surface improves fatiguelife; however, for EBM manufactured material, the extent of improvement is dependent on the amount of material removed. The as-built surface roughness, which has numerous crack initiation sites, leads to lower scatter in fatigue life. In both SLM and EBM manufactured material, fatigue crack propagation is transgranular. Crack propagation is affected by grain size and texture of the material.
|
|
| 7. |
- Balachandramurthi, Arun Ramanathan, et al.
(författare)
-
Influence of defects and as-built surface roughness on fatigue properties of additively manufactured Alloy 718
- 2018
-
Ingår i: Materials Science & Engineering. - : Elsevier BV. - 0921-5093 .- 1873-4936. ; 735, s. 463-474
-
Tidskriftsartikel (refereegranskat)abstract
- Electron beam melting (EBM) and Selective Laser Melting (SLM) are powder bed based additive manufacturing (AM) processes. These, relatively new, processes offer advantages such as near net shaping, manufacturing complex geometries with a design space that was previously not accessible with conventional manufacturing processes, part consolidation to reduce number of assemblies, shorter time to market etc. The aerospace and gas turbine industries have shown interest in the EBM and the SLM processes to enable topology-optimized designs, parts with lattice structures and part consolidation. However, to realize such advantages, factors affecting the mechanical properties must be well understood – especially the fatigue properties. In the context of fatigue performance, apart from the effect of different phases in the material, the effect of defects in terms of both the amount and distribution and the effect of “rough†as-built surface must be studied in detail. Fatigue properties of Alloy 718, a Ni-Fe based superalloy widely used in the aerospace engines is investigated in this study. Four point bending fatigue tests have been performed at 20 Hz in room temperature at different stress ranges to compare the performance of the EBM and the SLM material to the wrought material. The experiment aims to assess the differences in fatigue properties between the two powder bed AM processes as well as assess the effect of two post-treatment methods namely – machining and hot isostatic pressing (HIP). Fractography and metallography have been performed to explain the observed properties. Both HIPing and machining improve the fatigue performance; however, a large scatter is observed for machined specimens. Fatigue properties of SLM material approach that of wrought material while in EBM material defects severely affect the fatigue life. © 2018 Elsevier B.V.
|
|
| 8. |
- Balachandramurthi, Arun Ramanathan, 1989-, et al.
(författare)
-
Microstructural influence on fatigue crack propagation during high cycle fatigue testing of additively manufactured Alloy 718
- 2019
-
Ingår i: Materials Characterization. - : Elsevier BV. - 1044-5803 .- 1873-4189. ; 149, s. 82-94
-
Tidskriftsartikel (refereegranskat)abstract
- A study of the microstructure of additively manufactured Alloy 718 was performed in order to better understand the parameters that have an influence on the fatigue properties of the material. The specimens were manufactured using two powder bed fusion techniques – Electron Beam Melting (EBM) and Selective Laser Melting (SLM). Four point bending fatigue tests were performed at room temperature with a stress ratio of R = 0.1 and 20 Hz frequency, on material that was either in hot isostatically pressed (HIP) and solution treated and aged (STA) condition or in STA condition without a prior HIP treatment. The grains in the SLM material in the HIP + STA condition have grown considerably both in the hatch and the contour regions; EBM material, in contrast, shows grain growth only in the contour region. Fractographic analysis of the specimens in HIP + STA condition showed a faceted appearance while the specimens in STA condition showed a more planar crack appearance. The crack propagation occurred in a transgranular mode and it was found that precipitatessuch as NbC, TiN or δ-phase, when present, did not affect the crack path. The areas with larger grains corresponded to the faceted appearance of the fracture surface. This could be attributed to the plastic zone ahead of the crack tip being confined within one grain, in case of the larger grains, which promotes single shear crack growth mode
|
|
| 9. |
- Balachandramurthi, Arun Ramanathan, 1989-, et al.
(författare)
-
Microstructure tailoring in Electron Beam Powder Bed Fusion Additive Manufacturing and its potential consequences
- 2019
-
Ingår i: Results in Materials. - : Elsevier. - 2590-048X. ; 1
-
Tidskriftsartikel (refereegranskat)abstract
- Electron Beam Powder Bed Fusion process for Alloy 718 was investigated, in the sense of microstructural evolution with varying process conditions. The existence of a geometric relationship between the melt front and the processing parameters was observed. By understanding and capitalizing on this relationship, it was possible to obtain columnar, equiaxed or bimodal microstructure.
|
|
| 10. |
- Balachandramurthi, Arun Ramanathan, 1989-, et al.
(författare)
-
On the microstructure of laser beam powder bed fusion alloy 718 and its influence on the low cycle fatigue behaviour
- 2020
-
Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 13:22
-
Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing of Alloy 718 has become a popular subject of research in recent years. Understanding the process-microstructure-property relationship of additively manufactured Alloy 718 is crucial for maturing the technology to manufacture critical components. Fatigue behaviour is a key mechanical property that is required in applications such as gas turbines. Therefore, in the present work, low cycle fatigue behaviour of Alloy 718 manufactured by laser beam powder bed fusion process has been investigated. The material was tested in as-built condition as well as after two different thermal post-treatments. Three orientations with respect to the building direction were tested to evaluate the anisotropy. Testing was performed at room temperature under controlled amplitudes of strain. It was found that defects, inclusions, strengthening precipitates, and Young’s modulus influence the fatigue behaviour under strain-controlled conditions. The strengthening precipitates affected the deformation mechanism as well as the cycle-dependent hardening/softening behaviour. The defects and the inclusions had a detrimental effect on fatigue life. The presence of Laves phase in LB-PBF Alloy 718 did not have a detrimental effect on fatigue life. Young’s modulus was anisotropic and it contributed to the anisotropy in strain-life relationship. Pseudo-elastic stress vs. fatigue life approach could be used to handle the modulus-induced anisotropy in the strain-life relationship. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
|
|
| 11. |
- Balachandramurthi, Arun Ramanathan, et al.
(författare)
-
On the microstructure of laser beam powder bed fusion alloy 718 and its influence on the low cycle fatigue behaviour
- 2020
-
Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 13:22, s. 1-21
-
Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing of Alloy 718 has become a popular subject of research in recent years. Understanding the process-microstructure-property relationship of additively manufactured Alloy 718 is crucial for maturing the technology to manufacture critical components. Fatigue behaviour is a key mechanical property that is required in applications such as gas turbines. Therefore, in the present work, low cycle fatigue behaviour of Alloy 718 manufactured by laser beam powder bed fusion process has been investigated. The material was tested in as-built condition as well as after two different thermal post-treatments. Three orientations with respect to the building direction were tested to evaluate the anisotropy. Testing was performed at room temperature under controlled amplitudes of strain. It was found that defects, inclusions, strengthening precipitates, and Young’s modulus influence the fatigue behaviour under strain-controlled conditions. The strengthening precipitates affected the deformation mechanism as well as the cycle-dependent hardening/softening behaviour. The defects and the inclusions had a detrimental effect on fatigue life. The presence of Laves phase in LB-PBF Alloy 718 did not have a detrimental effect on fatigue life. Young’s modulus was anisotropic and it contributed to the anisotropy in strain-life relationship. Pseudo-elastic stress vs. fatigue life approach could be used to handle the modulus-induced anisotropy in the strain-life relationship.
|
|
| 12. |
- Balachandramurthi, Arun Ramanathan, 1989-
(författare)
-
Towards understanding the fatigue behaviour of Alloy 718 manufactured by Powder Bed Fusion processes
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Additive Manufacturing (AM) is a disruptive modern manufacturing process in which parts are manufactured in a layer-wise fashion. Among the metal AM processes, Powder Bed Fusion (PBF) technology — comprised of Electron Beam Powder Bed Fusion (EB-PBF) and Laser Beam Powder Bed Fusion (LB-PBF) —has opened up a design space that was formerly unavailable with conventionalmanufacturing processes. PBF processes offer several advantages; however, thesuitability of these processes to replace the conventional processes must be investigatedin detail. Therefore, understanding the AM process – post-processing –microstructure – property relationships is crucial for the manufacturing of high performance components. In this regard, only limited work has been done towards understanding the fatigue behaviour of PBF Alloy 718. The aim of this work, therefore, is to understand how the fatigue behaviour of PBF Alloy 718 is affected by its microstructure. Besides, the influence of the rough as-built surface is also investigated. In general, the <100> fibre texture along the build direction that resulted from PBF processing of Alloy 718 led to anisotropy in Young's modulus. Consequently,the fatigue performance under controlled amplitudes of strain was anisotropic such that the low-modulus direction had longer fatigue life and vice versa. This texture-induced elasticity-dependent anisotropic strain-life behaviour couldbe normalized by the pseudo-elastic stress vs fatigue life approach.Inclusions and defects had a detrimental effect on fatigue performance. Numerousfactors, such as their geometry, volume fraction, and distribution, determinedthe effect on fatigue behaviour. Hot Isostatic Pressing (HIP) eliminated most defect sand led to an improvement in fatigue performance. However, HIP did not alter the inclusions, which acted as crack initiation sites and reduced fatigue life. The rough as-built surface, which had numerous notch-like crack initiation sites, deteriorated fatigue performance; however, it lowered the scatter in fatigue life. Machining off the as-built surface improved fatigue life but increased the scatter.
|
|
| 13. |
- Balachandramurthi Ramanathan, Arun, et al.
(författare)
-
Additive Manufacturing of Alloy 718 via Electron Beam Melting : Effect of Post-Treatment on the Microstructure and the Mechanical Properties.
- 2018
-
Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Alloy 718 finds application in gas turbine engine components, such as turbine disks, compressor blades and so forth, due to its excellent mechanical and corrosion properties at elevated temperatures. Electron beam melting (EBM) is a recent addition to the list of additive manufacturing processes and has shown the capability to produce components with unique microstructural features. In this work, Alloy 718 specimens were manufactured using the EBM process with a single batch of virgin plasma atomized powder. One set of as-built specimens was subjected to solution treatment and ageing (STA); another set of as-built specimens was subjected to hot isostatic pressing (HIP), followed by STA (and referred to as HIP+STA). Microstructural analysis of as-built specimens, STA specimens and HIP+STA specimens was carried out using optical microscopy and scanning electron microscopy. Typical columnar microstructure, which is a characteristic of the EBM manufactured alloy, was observed. Hardness evaluation of the as-built, STA and HIP+STA specimens showed that the post-treatments led to an increase in hardness in the range of ~50 HV1. Tensile properties of the three material conditions (as-built, STA and HIP+STA) were evaluated. Post-treatments lead to an increase in the yield strength (YS) and the ultimate tensile strength (UTS). HIP+STA led to improved elongation compared to STA due to the closure of defects but YS and UTS were comparable for the two post-treatment conditions. Fractographic analysis of the tensile tested specimens showed that the closure of shrinkage porosity and the partial healing of lack of fusion (LoF) defects were responsible for improved properties. Fatigue properties were evaluated in both STA and HIP+STA conditions. In addition, three surface conditions were also investigated, namely the 'raw' as-built surface, the machined surface with the contour region and the machined surface without the contour region. Machining off the contour region completely together with HIP+STA led to significant improvement in fatigue performance.
|
|
| 14. |
- Blöndal, Viiu, et al.
(författare)
-
Allergic sensitisation and type-2 inflammation is associated with new-onset and persistent allergic disease
- 2023
-
Ingår i: Clinical and Translational Allergy. - : Wiley-Blackwell. - 2045-7022. ; 13:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease.Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow-up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type-2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN).Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05-12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20-22.7] and 6.32 [1.52-26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29-9.49] and 6.73 [2.00-22.6], respectively).Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy.
|
|
| 15. |
- Brommage, Robert, et al.
(författare)
-
NOTUM inhibition increases endocortical bone formation and bone strength
- 2019
-
Ingår i: Bone Research. - : Springer Science and Business Media LLC. - 2095-4700 .- 2095-6231. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- The disability, mortality and costs caused by non-vertebral osteoporotic fractures are enormous. Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures. Cortical bone is a major determinant of non-vertebral bone strength. To identify novel osteoporosis drug targets, we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable genes. Cortical bone thickness was substantially elevated in Notum(-/-) mice. NOTUM is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not osteoclasts. Three orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were developed. They increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone formation. Thus, inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.
|
|
| 16. |
- Calmunger, Mattias, et al.
(författare)
-
Characterization of austenitic stainless steels deformed at elevated temperature
- 2017
-
Ingår i: Metallurgical and Materials Transactions. A. - : Springer-Verlag New York. - 1073-5623 .- 1543-1940. ; 48A:10, s. 4525-4538
-
Tidskriftsartikel (refereegranskat)abstract
- Highly alloyed austenitic stainless steels are promising candidates to replace more expansive nickel-based alloys within the energy-producing industry. The present study investigates the deformation mechanisms by microstructural characterisation, mechanical properties and stress-strain response of three commercial austenitic stainless steels and two commercial nickel-based alloys using uniaxial tensile tests at elevated temperatures from 400 C up to 700 C. The materials showed different influence of temperature on ductility, where the ductility at elevated temperatures increased with increasing nickel and solid solution hardening element content. The investigated materials showed planar dislocation driven deformation at elevated temperature. Scanning electron microscopy showed that deformation twins were an active deformation mechanism in austenitic stainless steels during tensile deformation at elevated temperatures up to 700 C.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Calmunger, Mattias, et al.
(författare)
-
Surface Phase Transformation in Austenitic Stainless Steel Induced by Cyclic Oxidation in Humidified Air
- 2015
-
Ingår i: Corrosion Science. - : Pergamon Press. - 0010-938X .- 1879-0496. ; 100, s. 524-534
-
Tidskriftsartikel (refereegranskat)abstract
- The formation of α’ martensite at the surface of an AISI 304 stainless steel subjected to cyclic heating in humidified air is reported. The α’ martensite formed during the cooling part of the cyclic tests due to local depletion of Cr and Mn and transformed back to austenite when the temperature again rose to 650 °C. The size of the α’ martensite region increased with increasing number of cycles. Thermodynamical simulations were used as basis for discussing the formation of α’ martensite. The effect of the α’ martensite on corrosion is also discussed.
|
|
| 20. |
- Deng, Dunyong, et al.
(författare)
-
On the Dwell-Fatigue Crack Propagation Behavior of a High-Strength Ni-Base Superalloy Manufactured by Selective Laser Melting
- 2020
-
Ingår i: Metallurgical and Materials Transactions. A. - : SPRINGER. - 1073-5623 .- 1543-1940. ; 51, s. 962-972
-
Tidskriftsartikel (refereegranskat)abstract
- This study focuses on the dwell-fatigue crack propagation behavior of IN718 manufactured via selective laser melting (SLM). The dwell-fatigue test condition is 823 K (550 with a long 2160-s dwell-holding period. Effects of heat treatment and loading direction on dwell-fatigue crack propagation rates are studied. A grain boundary delta precipitate seems to be slightly beneficial to the dwell-fatigue cracking resistance of SLM IN718. A comparison has been made between SLM IN718 and forged counterparts at different temperatures, indicating that a creep damage mechanism is likely dominant for SLM IN718 under the present test condition. A general discussion of the inferior creep resistance of SLM IN718 is also included. The anisotropic dwell-fatigue cracking resistance has also been studied and rationalized with the effective stress intensity factor calculated from finite element modeling.
|
|
| 21. |
- Ebisawa, M., et al.
(författare)
-
Measurement of Ara h 1-, 2-, and 3-specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children
- 2012
-
Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 23:6, s. 573-581
-
Tidskriftsartikel (refereegranskat)abstract
- To cite this article: Ebisawa M, Moverare R, Sato S, Maruyama N, Borres MP, Komata T. Measurement of Ara h 1-, 2-, and 3-specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children. Pediatr Allergy Immunol 2012: 23: 573581. Abstract Background: Food challenges are time-consuming, expensive, and not always possible to perform. Therefore, new tools to diagnose food allergy are desired. The aim was to evaluate IgE antibodies to peanut allergens in the diagnosis of peanut allergy in Japanese children using ImmunoCAP (R) and IgE immunoblotting. Methods: The study included 213-yr-old consecutive patients (n = 57) referred to our specialist clinic for investigation of current peanut allergy using food challenge. All children had a previous doctors diagnosis of peanut allergy and were on elimination diet. Serum samples were analyzed for IgE reactivity to peanut, recombinant (r) Ara h 1, 2, 3, 5, 8, and 9. IgE immunoblotting (n = 23) was performed using extracts from raw and roasted peanut. Results: Twenty-six of the children failed (allergic group), and 31 passed the peanut challenge (tolerant group). The rAra h 2 ImmunoCAP test was superior in its ability to differentiate between children in the allergic and tolerant groups with a sensitivity and specificity of 88% and 84%, respectively (cutoff, 0.35 kUA/l). The combination of rAra h 1, 2, and 3 resulted in a higher specificity (94%) when IgE to all of them was the criteria for positivity. ImmunoCAP generally showed a good agreement with immunoblotting using both raw and roasted peanut for IgE reactivity to Ara h 1, 2, and 3. Conclusions: Measurement of IgE antibodies to rAra h 1, 2, and 3 is useful in the diagnosis of peanut allergy and in the investigation of reactions to raw and roasted peanut.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Eriksson, Robert, et al.
(författare)
-
A low cycle fatigue life model for a shot peened gas turbine disc alloy
- 2019
-
Ingår i: International Journal of Fatigue. - : ELSEVIER SCI LTD. - 0142-1123 .- 1879-3452. ; 124, s. 34-41
-
Tidskriftsartikel (refereegranskat)abstract
- Turbine disks in gas turbines are subjected to cyclic load at high temperature, making, especially the fir tree type blade attachments, susceptible to fatigue. Shot peening of the fir tree attachments may be used to increase the fatigue life by introducing compressive residual stresses. In the current study, both polished and shot peened notched specimens made from alloy 718 were subjected to low cycle fatigue at 450-550 degrees C. The shot peening generally increased the fatigue life, although the effect diminished for high loads. It was shown that the effect of shot peening could be handled as mean stress effects in a life model based on a Smith-Watson-Topper (SWT) type parameter, sigma(max)Delta epsilon/2. A material model which captured the mean stress was set up to get the SWT parameter at the notch root. It was shown that thermal relaxation of residual stresses and initial strain hardening from cold work could be excluded from the finite element analysis used to establish the mean stress; this since the plasticity in the first cycle dominated the plastic deformation of the specimen. Overall, the SWT-based life model worked satisfactorily. However, the prediction of correct mean stresses at 550 degrees C proved somewhat difficult as the degree of mean stress relaxation at this temperature varies widely in available literature data.
|
|
| 26. |
- Eriksson, Robert, et al.
(författare)
-
Evaluation of notch effects in low cycle fatigue of alloy 718 using critical distances
- 2018
-
Ingår i: 12TH INTERNATIONAL FATIGUE CONGRESS (FATIGUE 2018). - : E D P SCIENCES.
-
Konferensbidrag (refereegranskat)abstract
- Gas turbine disks contain many notch-like features acting as stress raisers. The fatigue life based on the notch root stress may be overly conservative as the steep stress gradient in front of the notch may give rise to so-called notch support. In the current work, the theory of critical distances was applied to the prediction of the total fatigue life of low cycle fatigued, notched specimens made from alloy 718. The fatigue tests were performed at 450 degrees C and 550 degrees C. It was found that, for lives shorter than 5000-10000 cycles, the notched specimens had longer lives than would have been expected based on the notch root strain. For lives longer than 5000-10000 cycles, there were no notch support. The life prediction for notched specimens could be significantly improved by basing the prediction on the strain chosen some distance from the notch (the critical distance). An expression for calculating the critical distance based on the notch root strain was suggested.
|
|
| 27. |
- Everberg, Henrik, et al.
(författare)
-
Affinity Purification of Egg-White Allergens for Improved Component-Resolved Diagnostics
- 2011
-
Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 154:1, s. 33-41
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Egg is a common cause of food-allergic reactions, especially among young children. Some egg-allergic patients do, however, tolerate heated egg products and component-resolved diagnostics (CRD) may facilitate prediction of different disease manifestations. Commercially available preparations of the egg-white allergens, ovomucoid, ovalbumin, conalbumin and lysozyme, have been reported to contain impurities which interfere with accurate CRD. Methods: Commercial preparations of the 4 egg-white allergens were characterized using allergen-specific monoclonal chimeric human/mouse IgE antibodies in experimental ImmunoCAP (R) tests. Further purification of commercial ovomucoid, ovalbumin and conalbumin preparations was performed by chromatography based on affinity to monoclonal antibodies. Purity was monitored by size exclusion chromatography, SDS-PAGE, Western blotting and experimental ImmunoCAP tests using allergen-specific chimeric IgE antibodies. IgE reactivity to the highly purified egg components was analyzed in 83 samples from egg white-sensitized individuals. Results: Preparations of commercially available ovomucoid, ovalbumin and conalbumin were found to contain other egg allergens which were removed by chromatographic purification. No impurities were detected in the commercial lysozyme preparation. Previously unknown complexes between the target allergens and contaminating allergens were detected and removed by affinity chromatography. IgE reactivity to ovalbumin was most common in the analyzed samples (87%), followed by ovomucoid (72%), conalbumin (69%) and lysozyme (58%). Conclusions: In this study we demonstrate the advantage of using monoclonal antibodies for purification, and monoclonal chimeric IgE antibodies for characterization, of egg allergens intended for CRD. Our study also established that ovalbumin, ovomucoid, conalbumin and lysozyme are all major allergens.
|
|
| 28. |
- Funck-Brentano, Thomas, et al.
(författare)
-
Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice
- 2018
-
Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 238:1, s. 13-23
-
Tidskriftsartikel (refereegranskat)abstract
- WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, mu CT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.
|
|
| 29. |
- Färdig, Martin, et al.
(författare)
-
Eosinophil-derived neurotoxin levels in early childhood and association with preschool asthma - A prospective observational study
- 2023
-
Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 53:11, s. 1198-1211
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Eosinophil-derived neurotoxin (EDN) is related to childhood asthma, while normal values are lacking. We aimed to document serum EDN levels at 1 and 3 years in general and in non-atopic children, and explore if EDN levels differed by sex or were associated with preschool asthma at 3 years.Methods: From the PreventADALL birth cohort, we included 1233 children with EDN analysed using ImmunoCAP at 1 and/or 3 years. Non-atopic children had no history of wheeze, asthma, allergic sensitization or atopic dermatitis. Preschool asthma was defined as having ≥3 episodes of bronchial obstruction between 2 and 3 years, plus doctor diagnosed asthma and/or asthma medication use by 3 years. The upper limit of normal (ULN) of EDN was defined as the 95th percentile. With Youden Index we calculated EDN cut-off levels for risk of preschool asthma.Results: The overall median (ULN) EDN levels were 27.4 (121) μg/L at 1 year (n = 787), and 20.1 (87.8) μg/L at 3 years (n = 857). Non-atopic children had EDN levels of 24.0 (107) μg/L at 1 year (n = 147), and 17.3 (84.6) μg/L at 3 years (n = 173). EDN levels were higher in boys compared to girls; 32.0 (133) versus 24.5 (97.0) μg/L at 1 year, and 20.9 (96.3) versus 19.0 (72.4) μg/L at 3 years. Preschool asthma was observed in 109/892 (12.2%) children. Higher EDN levels at 1 (>26.7 μg/L) and 3 (≥20.5 μg/L) years were associated with preschool asthma; adjusted OR (95% CI) 2.20 (1.09, 4.41) and 4.68 (2.29, 9.55), respectively.Conclusion and Clinical Relevance: We report EDN values in early childhood, demonstrating higher levels at 1 compared to 3 years and in boys compared to girls at both ages. Higher EDN levels at both ages were associated with preschool asthma. However, EDN cut-off levels for preschool asthma were overall lower than the ULN of non-atopic children, limiting translation into clinical practice.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Ito, Komei, et al.
(författare)
-
The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children
- 2012
-
Ingår i: Clinical and Molecular Allergy. - : Springer Science and Business Media LLC. - 1476-7961. ; 10:1, s. 1-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundCow's milk allergy is one of the most common food allergies among younger children. We investigated IgE antibodies to milk, and IgE and IgG4 antibodies to casein, α-lactalbumin and β-lactoglobulin in cow's milk allergic (CMA) and non-allergic (non-CMA) children in order to study their clinical usefulness.MethodsEighty-three children with suspected milk allergy (median age: 3.5 years, range: 0.8-15.8 years) were diagnosed as CMA (n = 61) or non-CMA (n = 22) based on an open milk challenge or convincing clinical history. Their serum concentrations of allergen-specific (s) IgE and IgG4 antibodies were measured using ImmunoCAP®. For the sIgG4 analysis, 28 atopic and 31 non-atopic control children were additionally included (all non-milk sensitized).ResultsThe CMA group had significantly higher levels of milk-, casein- and β-lactoglobulin-sIgE antibodies as compared to the non-CMA group. The casein test showed the best discriminating performance with a clinical decision point of 6.6 kUA/L corresponding to 100% specificity. All but one of the CMA children aged > 5 years had casein-sIgE levels > 6.6 kUA/L. The non-CMA group had significantly higher sIgG4 levels against all three milk allergens compared to the CMA group. This was most pronounced for casein-sIgG4 in non-CMA children without history of previous milk allergy. These children had significantly higher casein-sIgG4 levels compared to any other group, including the non-milk sensitized control children.ConclusionsHigh levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.
|
|
| 34. |
- Karsten, Carley, et al.
(författare)
-
Evaluating the Performance of Two Automated Anti-drug Antibodies Assays for Infliximab and Adalimumab Without Acid Dissociation
- 2024
-
Ingår i: AAPS Journal. - : Springer. - 1550-7416. ; 26:5
-
Tidskriftsartikel (refereegranskat)abstract
- Monitoring anti-drug antibodies (ADAs) to infliximab and adalimumab is critical to treatment management in various autoimmune disorders. The growing need for proactive therapeutic monitoring further requires the detection of ADAs in the presence of measurable concentrations of infliximab or adalimumab. To provide robust analytical assays for clinical application, we evaluated two automated immunoassays developed using ImmunoCAP™ technology and based on the bridging format to measure serum ADAs to infliximab and adalimumab respectively. Without an acid-dissociation step, these research prototype assays can detect a positive control monoclonal ADA towards infliximab and adalimumab, ranging from < 25 ng/ml to 10,000 ng/mL. Both assays exhibit imprecision less than 20% at different ADA titer levels and can distinguish ADAs towards different drug targets. In method comparison using authentic patient samples, the quantitative results of the ADA assays are not directly comparable to two existing clinical immunoassays for ADAs (correlation coefficient rs = 0.673 for infliximab ADAs; rs = 0.510 for adalimumab ADAs), presumably due to the lack of commutable ADA standards and the polyclonal nature of ADAs. Nevertheless, there is qualitative agreement between the methods when evaluating putative positive and negative patient samples (overall agreement 0.83 for infliximab ADAs; 0.76 for adalimumab ADAs). Biotin and high levels of rheumatoid factors may interfere with the performance of the automated assays due to competitive binding with the biotinylated drug and non-specific formation of bridging complexes. The two ImmunoCAP assays can provide new analytical methods for proactive therapeutic monitoring of adalimumab and infliximab.
|
|
| 35. |
- Kuitunen, M., et al.
(författare)
-
High IgE levels to -lactalbumin, -lactoglobulin and casein predict less successful cow's milk oral immunotherapy
- 2015
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 70:8, s. 955-962
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundA new treatment option for persistent cow's milk allergy (CMA) is oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG(4) antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome. MethodsSeventy-six children (5-17years) with challenge-verified CMA were subjected to a 6-month OIT protocol. The treatment aimed at reaching a maintenance dose of 200ml CM (high dose=HD). Those who did not reach target were analysed as a low-dose (LD) group. Sera were characterized before and after OIT regarding serum levels of IgE and IgG(4) to milk and five milk allergen components evaluated together with clinical CMA symptoms and outcome of OIT. ResultsFifty-five (72%) patients reached the maintenance dose (HD) during therapy. High specific IgE levels towards the milk allergens -lactalbumin (P=0.048), -lactoglobulin (P=0.006) and casein (P=0.015) before OIT start were associated with lower maintenance dose reached. Patients who developed desensitization had a larger increase in IgG(4) levels to -lactalbumin (P=0.034), -lactoglobulin (P=0.010), casein (P=0.047) and lactoferrin (P=0.030) during treatment than those who failed. ConclusionsComponent-resolved diagnostics before OIT can help to identify children with lower probability of a successful OIT outcome, as high IgE levels to -lactalbumin, -lactoglobulin and casein are associated with lower maintenance dose reached. An increase in the IgG(4) concentration to milk components during treatment indicated effective desensitization.
|
|
| 36. |
- Lindström, Stefan B., 1974-, et al.
(författare)
-
Service-life assessment of aircraft integral structures based on incremental fatigue damage modeling
- 2023
-
Ingår i: International Journal of Fatigue. - : Elsevier BV. - 0142-1123 .- 1879-3452. ; 172
-
Tidskriftsartikel (refereegranskat)abstract
- The Ottosen–Stenström–Ristinmaa (OSR) incremental fatigue damage model is adapted for fatigue-life assessment of integral airframes milled from 7050-T7451 aluminum plates. For validation, variable-amplitude high-cycle fatigue experiments are conducted for circumferentially notched, axisymmetric specimens, and for a geometry similar to an aircraft fuselage frame, with flanges, stiffeners, and web panels. We also describe how the parameters of the OSR model can be modified to account for surface roughness, and for setting acceptable failure probability.
|
|
| 37. |
|
|
| 38. |
- Lundkvist, M., et al.
(författare)
-
Characterization of anti-natalizumab antibodies in multiple sclerosis patients
- 2013
-
Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 19:6, s. 757-764
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A small proportion of multiple sclerosis (MS) patients treated with natalizumab develop anti-drug antibodies. Objective: The objective of this paper is to characterize the anti-natalizumab antibody response and to investigate differences between persistently and transiently antibody-positive patients. Methods: Screening for anti-natalizumab antibodies was performed using a standardized bridging ELISA. Antibody-positive samples were further analyzed for IgM and IgG1-4 antibodies using ELISA and ImmunoCAP (R). Results: Anti-natalizumab antibodies developed in 57 of 1379 (4.1%) treated patients after a median treatment duration of three months. Of the positive patients, 20 (35%) patients reverted to negative, 19 (33%) patients were confirmed persistently positive and 18 (32%) patients were unconfirmed positive. Significantly higher anti-natalizumab antibody levels were detected in persistently compared to transiently positive patients. A cutoff value predicting persistence of antibodies could be determined with a sensitivity of 0.84 and a specificity of 0.80. IgM and IgG4 antibody levels were significantly higher in persistently compared to transiently positive patients, and IgG1, IgG2 and IgG4 increased significantly over time. Conclusions: The level of total anti-natalizumab antibodies in a first positive sample can be used to predict patients at risk for persisting antibody positivity. However, neither IgM nor IgG1-4 antibodies could be used to discriminate between transiently and persistently positive patients.
|
|
| 39. |
|
|
| 40. |
- Maruyama, N., et al.
(författare)
-
Measurement of specific IgE antibodies to Ses i 1 improves the diagnosis of sesame allergy
- 2016
-
Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 46:1, s. 163-171
-
Tidskriftsartikel (refereegranskat)abstract
- Background The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. Objective The aim was to identify the allergen components useful to diagnose sesame-allergic children with the goal to reduce the number of OFCs needed. Methods Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). Results Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the best diagnostic performance of the allergen components in ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI, 0.826-0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95% CI, 0.589-0.805). The clinical sensitivity and specificity for the rSes i 1 ImmunoCAP test at optimal cut-off (3.96 kUA/L) were 86.1% and 85.7%, respectively. Conclusion and Clinical Relevance Sensitization to Ses i 1 is strongly associated with clinical sesame allergy. Measurement of specific IgE to rSes i 1 could reduce the numbers of OFCs needed.
|
|
| 41. |
- Mindus, Stephanie, et al.
(författare)
-
Respiratory symptoms, exacerbations and sleep disturbances are more common among participants with asthma and chronic airflow limitation : an epidemiological study in Estonia, Iceland and Sweden
- 2024
-
Ingår i: BMJ open respiratory research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic airflow limitation (CAL) is a hallmark of chronic obstructive pulmonary disease but is also present in some patients with asthma. We investigated respiratory symptoms, sleep and health status of participants with and without CAL with particular emphasis on concurrent asthma using data from adult populations in Iceland, Estonia and Sweden investigated within the Burden of Obstructive Lung Disease study.METHODS: All participants underwent spirometry with measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) before and after bronchodilation. CAL was defined as postbronchodilator FEV1/FVC below the lower limit of normal. IgE-sensitisation and serum concentrations of eosinophil-derived neurotoxin (S-EDN) were assessed in a subsample. The participants were divided into four groups: no self-reported doctor's diagnosed asthma or CAL, asthma without CAL, CAL without asthma and asthma and CAL: χ2 test and analysis of variance were used in bivariable analyses and logistic and linear regression when analysing the independent association between respiratory symptoms, exacerbations, sleep-related symptoms and health status towards CAL, adjusting for centre, age, sex, body mass index, smoking history and educational level.RESULTS: Among the 1918 participants, 190 (9.9%) had asthma without CAL, 127 (6.6%) had CAL without asthma and 50 (2.6%) had CAL with asthma. Having asthma with CAL was associated with symptoms such as wheeze (adjusted OR (aOR) 6.53 (95% CI 3.53 to 12.1), exacerbations (aOR 12.8 (95% CI 6.97 to 23.6), difficulties initiating sleep (aOR 2.82 (95% CI 1.45 to 5.48), nocturnal gastro-oesophageal reflux (aOR 3.98 (95% CI 1.79 to 8.82)) as well as lower physical health status. In these analyses, those with no asthma and no CAL were the reference group. The prevalence of IgE-sensitisation was highest in both asthma groups, which also had higher levels of S-EDN.CONCLUSION: Individuals with self-reported asthma with CAL suffer from a higher burden of respiratory and sleep-related symptoms, higher exacerbation rates and lower health status when compared with participants with asthma alone or CAL alone.
|
|
| 42. |
- Movérare, Robert, et al.
(författare)
-
Change in the pattern of IgE reactivity to timothy grass and birch pollen allergens over a 20-year period
- 2006
-
Ingår i: Journal of investigational allergology & clinical immunology. - 1018-9068 .- 1698-0808. ; 16:5, s. 274-278
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have shown that the prevalence of allergy and allergen sensitization has increased in recent years. However, the changes in the pattern of IgE reactivity to individual allergens are mostly unknown. Objective: The aim of this preliminary study was. to assess the change in IgE reactivity profile to individual timothy grass and/or birch pollen allergens in sera from sensitized individuals randomly collected 20 years apart. Methods: Serum samples from 51 sensitized individuals were obtained from 2 cross-sectional surveys performed in 1973 and 1994 using random samples from Vammala, Finland. The sera were analyzed for IgE reactivity to timothy grass and/or birch pollen extracts, recombinant (r)Phl p 1, 2, 5, 6, 7, 11, 12, native (n)Phl p 4, and rBet v 1, 2 and 4 by immunoassay (ImmunoCAP). Results: The median (range) concentrations of IgE antibodies to timothy grass and birch pollen were higher in 1994 than in 1973 (6.47 [0.35 to > 100] kU(A)/L vs 1.53 [0.40-25.3] kU(A)[L; P=.0035). The prevalence of IgE reactivity to some allergens was higher in 1994 than in 1973, particularly rPhl p 5 (52% vs 19%), rPhl p 6 (43% vs 12%), and rBet v 1 (100% vs 29%). There was a correlation between timothy grass pollen-specific serum IgE levels and the numbers of IgE reactivities to individual allergens (p=0.76, P <.001). Conclusions: The increase in specific IgE levels together with a possible increase in the prevalence of IgE reactivity to the major allergens Phl p 5 and Bet v 1 between 1973 and 1994 may have contributed to the increase in atopic conditions in Finland.
|
|
| 43. |
- Moverare, Robert, et al.
(författare)
-
Evaluation of IgE Antibodies to Recombinant Peanut Allergens in Patients with Reported Reactions to Peanut
- 2011
-
Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 156:3, s. 282-290
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Peanut may cause severe reactions in allergic individuals. The objective was to evaluate IgE antibodies to various recombinant (r) peanut and birch pollen allergens in relation to IgE levels to whole peanut extract and severe allergic reactions to peanut. Methods: Seventy-four Swedish peanut-allergic patients (age: 14-61 years) reported previous peanut exposure and associated symptoms using a questionnaire. Their IgE reactivity to peanut, birch pollen and individual allergen components was analyzed using ImmunoCAP(R). Results: Of the 48 subjects sensitized to Ara h 1, 2 or 3, 60% had peanut-specific IgE levels >15 kU(A)/l, while 100% of the subjects without detectable IgE to these allergens had low peanut-specific IgE levels (<10 kU(A)/l). The levels of IgE to rAra h 8, rBet v 1 and birch pollen were highly correlated (r(S) = 0.94, p < 0.0001). Fifty-eight patients reported adverse reactions after accidental or deliberate peanut exposure (oral, inhalation or skin) of whom 41 had IgE to rAra h 1, 2 or 3. Symptoms of respiratory distress were associated with sensitization to Ara h 1, 2 or 3 (56 vs. 18%, p < 0.01). Two cases of anaphylaxis were reported among the individuals sensitized to Ara h 1-3. IgE to rAra h 8, rAra h 9, profilin or cross-reactive carbohydrate determinants were not associated with severe symptoms. Conclusions: The results indicate that IgE reactivity to Ara h 1, 2 and 3 is associated with severe reactions after exposure to peanut in Swedish patients.
|
|
| 44. |
- Movérare, Robert, et al.
(författare)
-
Human Allergen-Specific IgG Subclass Antibodies Measured Using ImmunoCAP Technology
- 2017
-
Ingår i: International Archives of Allergy and Immunology. - : KARGER. - 1018-2438 .- 1423-0097. ; 172:1, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge of human IgG subclass antibody responses to various allergens has been hampered by a lack of reliable standardized assays. The aim here was to develop quantitative immunoassays for human IgG1, IgG2, and IgG3 antibodies using ImmunoCAP (R) technology and to evaluate their application. Methods: Enzyme conjugates with isotype-specific monoclonal antibodies and calibrators composed of purified myeloma paraproteins were developed for each assay and used together with other standardized assay reagents for the Phadia (R) 100 instrument. The calibrators were adjusted to the international reference preparation IRP 67/86. The assays were characterized and used together with other standard ImmunoCAP assays to measure antibodies to various allergens in preliminary studies. Results: The new assays had limits of quantitation of 1.0 (IgG1), 4.6 (IgG2), and 0.04 mg(A)/L (IgG3), and coefficients of variation of <20%. Only some minor cross -reactivity with IgG2 was observed for the specific IgG1 assay. The specific IgG2 assay showed a bias for the allotype G2m(23) and compensation factors were used to adjust the measured concentrations accordingly. Preliminary studies indicated a strong and stable IgG4 antibody response to P-lactoglobulin in healthy individuals, a high IgG1 and even higher IgG2 antibody response to house dust mite in sensitized and nonsensitized subjects, and a mixed IgG subclass response to venom allergens in allergic patients with increasing IgG4 antibody levels during venom immunotherapy. Conclusions: The new research assays are valuable tools for immunological studies, enabling the characterization of antibody profiles using a standardized approach, and facilitating data interpretation and the comparison of results across studies.
|
|
| 45. |
|
|
| 46. |
- Movérare, Robert
(författare)
-
Immunological mechanisms involved in seasonal pollen allergy and allergen-specific immunotherapy
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Th1/Th2-like T-cell responses were studied by stimulating peripheral blood mononuclear cells (PBMCs) with allergens or antigens followed by restimulation with mitogens to induce high cytokine synthesis. Allergen-stimulation in vitro induced Th2-skewed cytokine synthesis by PBMCs from birch-pollen-allergic patients. The IL-4 and IL-13 production correlated with theserum levels of allergen-specific IgE.Allergic patients were treated by conventional birch-pollen-specific immunotherapy (IT).After a short initial fall, there was a significant increase in allergen-specific proliferation andIL-4, IL-5 and IL-10 production by PBMCs when reaching the maintenance dose and duringthe subsequent pollen season. The increase in IL-4 correlated with a temporary increase inspecific serum IgE. The tetanus toxoid-specific IL-5 and IL-10 production was also increased,suggesting that systemic changes in the capacity to produce Th2-like cytokines might occurduring the early phase of IT. There was no indication of an immune deviation from Th2- toTh1/Th0-like immune response to allergens during 18 months of IT. The enhanced prolifera-tive response to allergens was absent in allergic patients after IT indicating that induction ofperipheral T-cell tolerance might be part of the mechanism.A pollen-specific rush IT (RIT) study was performed over three years. RIT was generallywell tolerated and led to significant clinical improvements. A fast increase in total and specificserum IgE during the early months of RIT was noticed followed by decreased levels. SpecificIgG and IgG4 increased continuously over a two-year period. Decreased medication duringthe third year of RIT correlated with the relative decrease in specific IgE.Measuring cytokine synthesis by allergen-stimulated PEMCs and antibody levels in serummay be useful in monitoring immunological responses during IT.
|
|
| 47. |
|
|
| 48. |
- Movérare, Robert, et al.
(författare)
-
Mugwort-Sensitized Individuals from North Europe, South Europe and North America Show Different IgE Reactivity Patterns
- 2011
-
Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 154:2, s. 164-172
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sensitization to weed pollen allergens at the molecular level is not fully understood. We studied IgE reactivity to the major mugwort allergen Art v 1 in relation to allergens from other weed pollen and cross-reactive components in mugwort-sensitized subjects. Methods: Art v 1 and Amb a 1 were affinity purified and coupled to experimental ImmunoCAP (R) tests. Samples from North Europe (n = 50), South Europe (n = 19) and North America (n = 41) were analyzed for IgE against mugwort pollen, weed allergen components, pan-allergens and cross-reactive carbohydrate determinants (CCDs). Results: The prevalence of IgE reactivity (> 0.35 kU(A)/l) to Art v 1 was significantly higher in samples from North Europe than in those from North America. IgE to Amb a 1 was more common in North America than in North and South Europe, while IgE to Par j 2 was common in South Europe, less common in North America, and absent in North Europe. IgE to Art v 3 in mugwort-allergic patients was more common in North Europe than in South Europe and North America, while IgE to Sal k 1 was similar between the areas. Subjects with an Art v 1/mugwort-specific IgE ratio < 0.5 had more often IgE to Amb a 1, profilin, polcalcin and CCDs than subjects with a ratio > 0.5. Conclusions: Mugwort-sensitized subjects have different IgE reactivity profiles to weed allergens, reflecting their exposure to various pollens. Subjects with a low ratio between the IgE levels to Art v 1 and mugwort have a diverse IgE reactivity profile, indicating a role for cross-reactive allergens in their mugwort sensitization.
|
|
| 49. |
- Movérare, Robert, et al.
(författare)
-
Purification and characterization of the major oak pollen allergen Que a 1 for component-resolved diagnostics using ImmunoCAP
- 2008
-
Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 146:3, s. 203-211
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to purify the major oak pollen allergen, Que a 1, to perform biochemical and immunological characterization of the allergen and to develop an experimental native (n) Que a 1 ImmunoCAP(R). METHODS: Que a 1 was purified from oak pollen extract using affinity chromatography and characterized by SDS-PAGE, two-dimensional (2D) PAGE, mass spectrometry (MS), N-terminal sequencing and specific IgE inhibition on ImmunoCAP. Samples from 16 subjects sensitized to oak pollen were analyzed by ImmunoCAP for IgE reactivity to nQue a 1, and recombinant (r)Bet v 1 and 2 (profilin). They were also studied in IgE immunoblotting. RESULTS: The purity of nQue a 1 was >95%, since a single band was observed on silver-stained SDS-PAGE. The identity was verified by MS analysis, and 2D-PAGE revealed several isoforms. The obtained N-terminal sequence of 50-amino-acid residues from nQue a 1 showed a 58-74% sequence identity with other pathogenesis-related class 10 allergens. Specific IgE inhibition verified a preserved immunoreactivity (70-92% inhibition). All subjects were sensitized to Que a 1 and Bet v 1, and two to profilin. The IgE antibody levels to nQue a 1 were generally lower than to rBet v 1. The obtained results correlated well with IgE immunoblotting. CONCLUSIONS: We present a highly purified and extensively characterized preparation of nQue a 1. Que a 1 seems to be an allergen of equal importance in oak pollen as Bet v 1 in birch pollen. An nQue a 1 ImmunoCAP will be useful in component-resolved diagnostics.
|
|
| 50. |
- Movérare, Robert, et al.
(författare)
-
Reference values of serum total IgE in Uppsala : comparison over four decades
- 2023
-
Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 128
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Total immunoglobulin E (IgE) analysis is a common tool in allergy diagnosis. Suggested reference values for IgE are divergent and sometimes based on outdated assay methods. We aimed to validate the published reference values (geometric mean [GM]: 13.2 kU/L, upper limit of normal [ULN], 114 kU/L) shown in an Uppsala cohort from 1974 using Phadebas IgE PRIST, and the suggested clinical threshold of 100 kU/L (Zetterström and Johansson 1981).METHODS: Immunoglobulin E was measured in two Uppsala cohorts from 1997 (Blood bank) and 2011 to 2013 (the European community respiratory health survey part III [ECRHS III]) using ImmunoCAP™ Total IgE. For the reference value calculations, exclusion criteria were atopy (both cohorts), doctor's diagnosis of asthma and self-reported allergy (hay fever, rhinitis, rash) (only ECRHS III). Upper limit of normal was defined as mean + 2 standard deviations (SD) calculated using log-transformed values and back-transformation of the ULN prior to presentation. Common imputation methods for results below the assay range were evaluated.RESULTS: The average GM was 14.2 kU/L (Blood bank, n = 63; imputation method range: 16.9-17.4 kU/L; ECRHS III, n = 113: 10.7-11.6 kU/L) and the overall mean ULN was 118 kU/L (Blood bank: 113-130 kU/L; ECRHS III: 104-128 kU/L). The clinical sensitivity and specificity of the 100 kU/L IgE threshold were 37.8 and 94.3% for atopy, 34.9 and 89.5% for doctor's diagnosis of asthma, and 24.5 and 97.3% for any self-reported allergy (ECRHS III).CONCLUSION: The calculated ULN values were similar between the cohorts. We conclude that the total IgE reference values shown for Uppsala subjects from 1974 are still valid and suitable also for the ImmunoCAP Total IgE assay. The 100 kU/L threshold for total IgE had a low sensitivity but high specificity for atopy, asthma, and allergy.
|
|
