| 1. |
- Burkill, Sarah, et al.
(author)
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The DQB1* 03:02 Genotype and Treatment for Pain in People With and Without Multiple Sclerosis
- 2020
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In: Frontiers in Neurology. - : Frontiers. - 1664-2295. ; 11
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Journal article (peer-reviewed)abstract
- Murine models have demonstrated that the major histocompatibility complex (MHC) is associated with pain-like behavior in peripheral nerve injury, however, the same association has not been shown when considering injury to the central nervous system (CNS), which more closely mimics the damage to the CNS experienced by MS patients. Previous research has indicated the DQB1*03:02 allele of the class II HLA genes as being associated with development of neuropathic pain in persons undergoing inguinal hernia surgery or with lumbar spinal disk herniation. Whether this HLA allele plays a part in susceptibility to pain, has not, as far as we are aware, been previously investigated. This study utilizes information on DQB1*03:02 alleles as part of the EIMS, GEMS, and IMSE studies in Sweden. It also uses register data for 3,877 MS patients, and 4,548 matched comparators without MS, to assess whether the DQB1*03:02 allele is associated with prescribed pain medication use, and whether associations with this genotype differ depending on MS status. Our results showed no association between the DQB1*03:02 genotype and pain medication in MS patients, with an adjusted odds ratio (OR) of 1.02 (95% CI 0.85-1.24). In contrast, there was a statistically significant association of low magnitude in individuals without MS [adjusted OR 1.18 (95% CI 1.03-1.35)], which provides support for HLA influence on susceptibility to pain in the general population. Additionally, the effect of zygosity was evident for the non-MS cohort, but not among MS patients, suggesting the DQB1*03:02 allele effect is modified by the presence of MS.
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| 2. |
- Hammarsten, Ola, et al.
(author)
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The ratio of cardiac troponin T to troponin I may indicate non-necrotic troponin release among COVID-19 patients
- 2022
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In: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 527, s. 33-37
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Journal article (peer-reviewed)abstract
- Background: Although cardiac troponin T (cTnT) and troponin I(cTnI) are expressed to similar amount in cardiac tissue, cTnI often reach ten-times higher peak levels compared to cTnT in patients with myocardial necrosis such as in acute myocardial infarction (MI). In contrast, similar levels of cTnT and cTnI are observed in other situations such as stable atrial fibrillation and after strenuous exercise.Objective: Examine cTnT and cTnI levels in relation to COVID-19 disease and MI. Methods: Clinical and laboratory data from the local hospital from an observational cohort study of 27 patients admitted with COVID-19 and 15 patients with myocardial infarction (MI) that were analyzed with paired cTnT and cTnI measurement during hospital care.Results: Levels of cTnI were lower than cTnT in COVID-19 patients (TnI/TnT ratio 0.3, IQR: 0.1-0.6). In contrast, levels of cTnI were 11 times higher compared to cTnT in 15 patients with MI (TnI/TnT ratio 11, IQR: 7-14). The peak cTnI/cTnT ratio among the patients with MI following successful percutaneous intervention were 14 (TnI/ TnT ratio 14, IQR: 12-23). The 5 COVID-19 patient samples collected under possible necrotic events had a cTnI/ cTnT ratio of 5,5 (IQR: 1,9-8,3).Conclusions: In patients with COVID-19, cTnT is often elevated to higher levels than cTnI in sharp contrast to patients with MI, indicating that the release of cardiac troponin has a different cause in COVID-19 patients.
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| 3. |
- Leopold, Tobias, et al.
(author)
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Feasibility of photodetachment isobar suppression of WF5- with respect to HfF5
- 2014
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In: International Journal of Mass Spectrometry. - : Elsevier BV. - 1387-3806 .- 1873-2798. ; 359, s. 12-18
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Journal article (peer-reviewed)abstract
- The feasibility of using laser photodetachment as a means for isobar suppression in accelerator mass spectrometry has been investigated for the special case of HfF5-/WF5-. A method for absolute photodetachrnent cross section measurements was applied and the cross sections of tungsten pentafluoride and hafnium pentafluoride negative ions were measured. The measurements indicate that the photodetachment cross section for WF5- is at least 100 times larger than for HfF5- at the wavelength of the fourth harmonic of the Nd:YAG laser at 266 nm. The absolute cross section for WF5- at this photon energy was found to be (2.8 +/- 0.3) x 10(-18) cm(2), while an upper limit of 2 x 10(-2) cm(2) was obtained for the HfF5- cross section. The measured cross sections indicate that an optical filtering scheme for isobar suppression in accelerator mass spectrometry for the case of Hf-182 should be feasible. (C) 2013 Elsevier B.V. All rights reserved.
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| 4. |
- Lindahl, Anton, 1982, et al.
(author)
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Experimental studies of partial photodetachment cross sections in K- below the K(7 2P) threshold
- 2012
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In: Physical Review A. - : American Physical Society. - 1050-2947. ; 85:3
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Journal article (peer-reviewed)abstract
- A collinear beams apparatus has been used to determine photodetachment cross sections for K− in the photon energy range 4.250–4.360 eV. State-selective detection, utilizing a resonance ionization scheme, was applied to measure partial cross sections for those channels which leave the residual K atoms in the excited 7 2S, 5 2F, and 5 2G states. The energy region studied encompassed the openings of the aforementioned channels, as well as the channel that leaves the K atom in the 7 2P state. Two previously unobserved resonances were seen in all three partial cross sections between the K(5 2G) and K(7 2P) thresholds. It is shown that a more reliable determination of resonance parameters can be made if the same resonances are observed in several channels. In the region below the K(5 2F) threshold, three previously observed resonances were investigated [Kiyan et al. Phys. Rev. Lett. 84 5979 (2000)]. A greatly increased modulation of the signal was obtained by detecting in the K(7 2S) channel instead of the K(5 2S) channel used in the previous study. Furthermore, the shapes of the cross sections in the threshold regions are discussed. A detailed description of the apparatus and the experimental procedure employed is presented in the paper.
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| 5. |
- Lindahl, Anton, 1982, et al.
(author)
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Observation of thresholds and overlapping resonances below the 10(2)P(1/2) and P-2(3/2) thresholds in the photodetachment of Cs
- 2013
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In: Physical Review A. - 1050-2947. ; 88:5
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Journal article (peer-reviewed)abstract
- A collinear beam apparatus has been used to study photodetachment of Cs-. Partial cross sections were measured using state-selective detection based on a resonance ionization scheme. Several resonances were observed in the Cs(10(2)S), Cs(6 2F), Cs(6 2G), and Cs(6 2H) final-state channels below the Cs(10(2)P3/2) channel opening. A model was developed to account for the interference between overlapping resonances. This model is essentially a generalization of the Fano [U. Fano, Phys. Rev. 124, 1866 (1961)] and Shore [B. W. Shore, Phys. Rev. 171, 43 (1968)] parametrizations for single resonances. Resonance parameters were extracted by fitting the model to the data sets. The openings of the Cs(10(2)S) and Cs(6 2F) channels, where the polarizabilities of the atomic states are large and positive, showed rapid onsets. In the case of the Cs(6(2)G) and Cs(6(2)H) channels, on the other hand, the photodetachment cross sections increased slowly with energy. For the Cs(6(2)H) channel this is the expected behavior, since it is the result of a large and negative polarizability of the 6(2)H state. In addition, the excitation of the Cs(6(2)H) state with respect to the Cs ground state was found to be 28 356.3(2) cm(-1), in agreement with a previous experiment.
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| 6. |
- Lindahl, Anton, 1982, et al.
(author)
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Threshold behaviour in photodetachment of K-
- 2012
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In: Journal of Physics: Conference Series (XXVII International Conference on Photonic, Electronic and Atomic Collisions (ICPEAC 2011)). - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 388:PART 2
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Conference paper (peer-reviewed)abstract
- A photodetachment experiment has been performed with the formation of atoms in highly excited states of high positive and negative polarizabilities. A semiclassical model has been developed to describe the effect of the repulsive polarization potential in the vicinity of the photoreaction threshold.
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| 7. |
- Lindahl, Anton, 1982, et al.
(author)
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Threshold Photodetachment in a Repulsive Potential
- 2012
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In: Physical Review Letters. - : American Physical Society. - 0031-9007. ; 108:3
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Journal article (peer-reviewed)abstract
- We report on the first experimental observation of a new threshold behavior observed in the 5 2G partial channel in photodetachment of K-. It arises from the repulsive polarization interaction between the detached electron and the residual K(5 2G) atom, which has a large negative dipole polarizability. In order to account for the observation in the K(5 2G) channel, we have developed a semiclassical model that predicts an exponential energy dependence for the cross section. The measurements were made with collinear laser-ion beams and a resonance ionization detection scheme.
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| 8. |
- Lindahl, Hannes, et al.
(author)
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IL-22 Binding Protein Promotes the Disease Process in Multiple Sclerosis
- 2019
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In: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 203:4, s. 888-898
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have mapped the specific sequence variants that predispose for multiple sclerosis (MS). The pathogenic mechanisms that underlie these associations could be leveraged to develop safer and more effective MS treatments but are still poorly understood. In this article, we study the genetic risk variant rs17066096 and the candidate gene that encodes IL-22 binding protein (IL-22BP), an antagonist molecule of the cytokine IL-22. We show that monocytes from carriers of the risk genotype of rs17066096 express more IL-22BP in vitro and cerebrospinal fluid levels of IL-22BP correlate with MS lesion load on magnetic resonance imaging. We confirm the pathogenicity of IL-22BP in both rat and mouse models of MS and go on to suggest a pathogenic mechanism involving lack of IL-22-mediated inhibition of T cell-derived IFN-gamma expression. Our results demonstrate a pathogenic role of IL-22BP in three species with a potential mechanism of action involving T cell polarization, suggesting a therapeutic potential of IL-22 in the context of MS.
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| 9. |
- Lindahl, Hannes
(author)
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Interleukin-22 binding protein in multiple sclerosis and experimental inflammation models
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults. Although the cause of the disease is unknown, several genetic and environmental risk factors have been identified. By studying these risk factors in experimental systems we can learn more about the biological events that precede overt disease and then use this knowledge in the development of better and safer MS treatments. The aim of the work presented in this thesis is to shed light on one of the established genetic risk factors, the single nucleotide polymorphism (SNP) rs17066096. Since this SNP is positioned close to the gene IL22RA2, we hypothesize that IL22RA2 mediates the effect on MS susceptibility. The gene product of IL22RA2 is interleukin-22 binding protein (IL-22BP), a soluble IL-22 antagonist. Consequently, in study I-IV below, we focus on the role of the IL-22-system in MS and experimental inflammation models. In study I we reveal the role of IL-22BP in MS animal model experimental autoimmune encephalomyelitis (EAE). Il22ra2-deleted mice have less severe paralysis, immune cell infiltration, and demyelination compared to wild type mice. In study II we further investigate the biology of IL-22BP in inflammation. We use the mouse strain from study I, but now in two skin inflammation models: contact hypersensitivity and an imiquimod-induced psoriasis model. In contrast to EAE, the Il22ra2-deleted mice have more severe disease in both skin inflammation models. In study III we show that the risk genotype of rs17066096 is associated with higher expression of IL22RA2 in monocyte-derived dendritic cells from healthy blood donors and that MS patients with more lesions on magnetic resonance imaging have higher cerebrospinal fluid levels of IL-22BP. Using an inducible Il22ra2-knockdown rat strain we show that a relatively modest decrease in Il22ra2 expression is enough to make the rats resistant to EAE. Similarly, heterozygous deletion of Il22ra2 in mice is sufficient to achieve a protective effect. Furthermore, we establish that the protective effect in Il22ra2-deleted mice is dependent on the presence of IL-22. In study IV we investigate the effect of IL-22 signaling on the initiation of an adaptive immune response. Using the rat strain from study III, we show that knockdown of Il22ra2 expression just prior to immunization causes a reduction in lymphocyte expansion, preferentially affecting B cells, as well as a reduction in antigen specific effector functions in B cells and Th1 cells. In conclusion, we present data in support of a disease-promoting role for IL-22BP in neuroinflammation in three species. We show that the effect is dependent on IL-22, which consequently has a therapeutic potential.
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| 10. |
- Lindahl, Hannes, et al.
(author)
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SARS-CoV-2 Antibodies in Commercial Immunoglobulin Products Show Markedly Reduced Cross-reactivities Against Omicron Variants
- 2023
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In: Journal of Clinical Immunology. - : Springer Nature. - 0271-9142 .- 1573-2592. ; 43:6, s. 1075-1082
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Journal article (peer-reviewed)abstract
- PurposePatients with antibody deficiencies often receive maintenance treatment with donor plasma-derived immunoglobulin (Ig) preparations to decrease the incidence and severity of infections. We have previously shown that IgG antibodies to the original SARS-CoV-2 strain were not consistently present in off-the-shelf Ig batches produced up to approximately 18 months after the first identified case of COVID-19 in the USA and that Ig batches with anti-SARS-CoV-2 IgG primarily contained vaccine-induced spike specific antibodies. This study aimed to investigate the degree of cross-reactivity between vaccine-induced anti-SARS-CoV-2 antibodies against Wuhan strain and subsequent viral variants.MethodsSamples were collected from 74 Ig batches supplied by three different commercial manufacturers. All batches were used at the Immunodeficiency Unit at the Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until September 2022. Antibody quantity and potential to neutralize virus entry into host cells were assessed against the original SARS-CoV-2 Wuhan strain and the following nine variants: Alpha, Beta, Delta, IHU, and the Omicron BA.1, BA.1.1, BA.1 with spike mutation L452R, BA.2, and BA.3.ResultsIg batches produced approximately 18 months after the SARS-CoV-2 outbreak (from around July 2021) and later consistently contained high quantities of antibodies that bind the Wuhan strain. The Ig batches had overall low reactivity to the SARS-CoV-2 nucleocapsid, which implies that plasma donor spike IgG essentially is the result of vaccination. We assessed the degree of cross-reactivity towards each virus variant by plotting the variant/Wuhan strain ratio, which was consistent regardless of production date, suggesting cross-reactivity with vaccine-induced antibodies rather than virus exposure in the plasma donor population. Viral variants that emerged later during the pandemic systematically had a lower reactivity ratio, except for the Delta and IHU variants. The Ig batches displayed markedly low neutralizing potential towards the Beta variant and all tested Omicron variants.ConclusionCommercial Ig batches currently contain large quantities of SARS-CoV-2 vaccine-induced antibodies. Cross-reactivity with variant strains is evident but varies, with markedly low neutralizing potential observed against Omicron variants.
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