| 1. |
- Alsterholm, Mikael, 1977, et al.
(författare)
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Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy
- 2023
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
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| 2. |
- Stener-Victorin, Elisabet, 1964, et al.
(författare)
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Perceptual matching for assessment of itch; reliability and responsiveness analyzed by a rank-invariant statistical method.
- 2003
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Ingår i: The Journal of investigative dermatology. - : Elsevier BV. - 0022-202X. ; 121:6, s. 1301-5
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the reliability and responsiveness of a new device-perceptual matching by Matcher (Cefar Medical AB, Lund, Sweden)-in the assessment of the progress of experimentally induced itch as well as determine the reliability of the method in patients with skin disease and itch. The perceptual matching unit electrically stimulates the skin of the fingers in the left hand. When the amplitude of the sensation corresponded to that of the experienced itch, the subject was instructed to halt the stimulation and a value was automatically saved in the electronic device. A total of 36 healthy subjects and nine patients participated in the study. The healthy subjects were asked to rate the level of itch every 30 s during the first 5 min and thereafter every minute. The reliability was determined in a test-retest procedure of the time points 5, 10, and 15 min after induction of itching. To test the stability of the method, the first sensation of pain in healthy subjects without itch was determined every 10th minute during 60 min. In patients, the test-retest procedure was repeated within 5 min. Perceptual matching was found to be a reliable method of itch assessment, with no evidence for random individual disagreement between the assessments. The augmented rank order coefficient ra was excellent: 1.00 at 5 min; 0.99 at 10 min; and 1.00 at 15 min. There was a clear indication of responsiveness for detecting changes in itch over time, p
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| 3. |
- Acevedo, Nathalie, et al.
(författare)
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Epigenetic alterations in skin homing CD4(+)CLA(+) T cells of atopic dermatitis patients
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- T cells expressing the cutaneous lymphocyte antigen (CLA) mediate pathogenic inflammation in atopic dermatitis (AD). The molecular alterations contributing to their dysregulation remain unclear. With the aim to elucidate putative altered pathways in AD we profiled DNA methylation levels and miRNA expression in sorted T cell populations -(CD4(+), -CD4(+)CD45RA(+) naive, -CD4(+)CLA(+), and -CD8(+)) from adult AD patients and healthy controls (HC). Skin homing -CD4(+)CLA(+) T cells from AD patients showed significant differences in DNA methylation in 40 genes compared to HC (p < 0.05). Reduced DNA methylation levels in the upstream region of the interleukin-13 gene (IL13) in -CD4(+)CLA(+) T cells from AD patients correlated with increased IL13 mRNA expression in these cells. Sixteen miRNAs showed differential expression in -CD4(+)CLA(+) T cells from AD patients targeting genes in 202 biological processes (p < 0.05). An integrated network analysis of miRNAs and CpG sites identified two communities of strongly interconnected regulatory elements with strong antagonistic behaviours that recapitulated the differences between AD patients and HC. Functional analysis of the genes linked to these communities revealed their association with key cytokine signaling pathways, MAP kinase signaling and protein ubiquitination. Our findings support that epigenetic mechanisms play a role in the pathogenesis of AD by affecting inflammatory signaling molecules in skin homing -CD4(+)CLA(+) T cells and uncover putative molecules participating in AD pathways.
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| 4. |
- Axberg Pålsson, Sandra, et al.
(författare)
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Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children. Currently, there is no RSV vaccine or universally accessible antiviral treatment available. Addressing the urgent need for new antiviral agents, we have investigated the capacity of a non-coding single-stranded oligonucleotide (ssON) to inhibit RSV infection. By utilizing a GFP-expressing RSV, we demonstrate that the ssON significantly reduced the proportion of RSV infected A549 cells (lung epithelial cells). Furthermore, we show that ssON's antiviral activity was length dependent and that both RNA and DNA of this class of oligonucleotides have antiviral activity. We reveal that ssON inhibited RSV infection by competing with the virus for binding to the cellular receptor nucleolin in vitro. Additionally, using a recombinant RSV that expresses luciferase we show that ssON effectively blocked RSV infection in mice. Treatment with ssON in vivo resulted in the upregulation of RSV-induced interferon stimulated genes (ISGs) such as Stat1, Stat2, Cxcl10, and Ccl2. This study highlights the possibility of using oligonucleotides as therapeutic agents against RSV infection. We demonstrate that the mechanism of action of ssON is the inhibition of viral entry in vitro, likely through the binding of the receptor, nucleolin and that ssON treatment against RSV infection in vivo additionally results in the upregulation of ISGs.
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| 5. |
- Bergenstråhle, Joseph, et al.
(författare)
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Spatial transcriptomic profiling of RespiratorySyncytial Virus (RSV) infection
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Despite the fact that the human Respiratory Syncytial Virus (RSV) was first discoveredback in 1956, it remains one of the leading causes of morbidity and mortality inyoung children. Transcriptome-wide spatially resolved transcriptomics is a technologyunder rapid development that introduces a new modality for exploratory examinationof cellular behavior. With this modality, we examine how RSV infection changes thelocal cellular environment in the lung by infecting mice with RSV and comparing itto control samples four days after infection. We find viral presence in all compartmentsof the tissue, well-defined induced tertiary lymphoid tissue within some of thesamples, compartmentalized infiltration of innate immune cells, as well as functionalenrichment of airway epithelial repair pathways.
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| 6. |
- Bondesson Lundeberg, Lena
(författare)
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Interaction between the nervous and immune systems in allergic contact dermatitis : a clinical and experimental study with emphasis on the role of VIP and serotonin
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The interaction between the nervous and immune systems was investigated in allergic contact dermatitis (ACD) with emphasis on the role of vasoactive intestinal peptide (VIP) and serotonin (S-HT). Dual dose-dependent effects of VIP on the migration of mononuclear and polymorphonuclear leukocytes were found. Serotonin and the serotonin antagonists ketanserin, methiotepin and tropisetron had an inhibitory effect on the migration of mononuclear leukocytes while no effect on polymorphonuclear leukocytes. In pharmacological concentrations at least, VIP may protect lymphocytes from metal toxicity. Topical application of VIP on the established patch test reaction to nickel sulphate and intracutaneous injection of VIP in the challenge phase caused a reduction of the diameter of the test reaction. In addition, CD4+ cells were reduced in number when VIP was topically applied. The secretion of interferon gamma increased when VIP was added to cultures of peripheral blood mononuclear cells from nickel-allergic subjects in both challenge and proliferative phase. Of serotonin and its antagonists, ketanserin reduced the diameter of the test reaction when applied topically. Basal epidermal serotonin immunoreactive (IR) cells found were possibly melanocytes. These cells became more dendritic and migrated upwards in the epidermis in the ACD reaction, compared with in control skin. There was also an increased concentration of serotonin in ACD vis-a-vis control skin. There was no significant difference in either distribution of VIP fibres or concentration of VIP between ACD-involved and uninvolved skin. However, the number of dermal mononuclear cells showing VIP2 receptor-IR in ACD skin was reduced. In conclusion, VIP and serotonin may play a pathophysiological role in ACD, and both VIP and ketanserin may have therapeutic potential.
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| 7. |
- Huttner, Hagen B, et al.
(författare)
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The age and genomic integrity of neurons after cortical stroke in humans
- 2014
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 17:6, s. 801-803
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Tidskriftsartikel (refereegranskat)abstract
- It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.
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| 8. |
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| 9. |
- Johansson, Catharina, et al.
(författare)
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Elevated Peripheral Allergen-Specific T Cell Response Is Crucial for a Positive Atopy Patch Test Reaction
- 2009
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 150:1, s. 51-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atopic eczema is a chronic inflammatory skin disease in which several subgroups of cases can be identified. Atopy patch testing (APT) reveals allergen sensitization also in atopic eczema patients devoid of detectable allergen-specific IgE, suggesting the importance of factors other than IgE in the reaction. Here we investigate the relationship between APT reactions and allergen-specific peripheral IgE and T cell reactivity in atopic eczema patients. Methods: Adult patients with atopic eczema (n = 64) and healthy controls (n = 24) were analyzed for reactivity to Malassezia sympodialis extract by APT, measurement of specific plasma IgE and in vitro determination of the frequency of allergen-reactive peripheral blood mononuclear cells producing interleukin-4 and interleukin-5 using the ELISpot method. Results: When combining the results of the APT, IgE measurements and the ELISpot analyses, reactivity to M. sympodialis was found in a majority of the atopic eczema patients (69%), whereas the healthy controls were negative throughout. T cell reactivity to M. sympodialis, manifested by production of both interleukins 4 and 5, was highly predictive for a positive APT reaction and displayed a strongly positive correlation with the APT score. In contrast, the allergen-specific IgE levels did not predict the APT outcome, and no correlation could be found between the IgE levels and the APT score. Conclusion: Peripheral allergen-specific T helper 2 cell-mediated reactivity appears to be required for a positive APT reaction to M. sympodialis. The diagnostic potential of measuring peripheral allergen-specific T cell responses should be considered in atopic eczema.
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| 10. |
- Järver, Peter, et al.
(författare)
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Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream ofTLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.
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| 11. |
- Kvastad, Linda, et al.
(författare)
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The spatial RNA integrity number assay for in situ evaluation of transcriptome quality
- 2021
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- The RNA integrity number (RIN) is a frequently used quality metric to assess the completeness of rRNA, as a proxy for the corresponding mRNA in a tissue. Current methods operate at bulk resolution and provide a single average estimate for the whole sample. Spatial transcriptomics technologies have emerged and shown their value by placing gene expression into a tissue context, resulting in transcriptional information from all tissue regions. Thus, the ability to estimate RNA quality in situ has become of utmost importance to overcome the limitation with a bulk rRNA measurement. Here we show a new tool, the spatial RNA integrity number (sRIN) assay, to assess the rRNA completeness in a tissue wide manner at cellular resolution. We demonstrate the use of sRIN to identify spatial variation in tissue quality prior to more comprehensive spatial transcriptomics workflows. Kvastad et al. develop the spatial RNA Integrity Number (sRIN) assay that evaluates the RNA integrity at cellular resolution. This method improves the resolution of a similar method called the RNA Integrity Number (RIN), demonstrating spatial variation in the quality of RNA samples.
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| 12. |
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| 13. |
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| 14. |
- Poux, Candice, et al.
(författare)
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A Single-Stranded Oligonucleotide Inhibits Toll-Like Receptor 3 Activation and Reduces Influenza A (H1N1) Infection
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The initiation of an immune response is dependent on the activation and maturation of dendritic cells after sensing pathogen associated molecular patterns by pattern recognition receptors. However, the response needs to be balanced as excessive pro-inflammatory cytokine production in response to viral or stress-induced pattern recognition receptor signaling has been associated with severe influenza A virus (IAV) infection. Here, we use an inhibitor of Toll-like receptor (TLR)3, a single-stranded oligonucleotide (ssON) with the capacity to inhibit certain endocytic routes, or a TLR3 agonist (synthetic double-stranded RNA PolyI:C), to evaluate modulation of innate responses during H1N1 IAV infection. Since IAV utilizes cellular endocytic machinery for viral entry, we also assessed ssON's capacity to affect IAV infection. We first show that IAV infected human monocyte-derived dendritic cells (MoDC) were unable to up-regulate the co-stimulatory molecules CD80 and CD86 required for T cell activation. Exogenous TLR3 stimulation did not overcome the IAV-mediated inhibition of co-stimulatory molecule expression in MoDC. However, TLR3 stimulation using PolyI:C led to an augmented pro-inflammatory cytokine response. We reveal that ssON effectively inhibited PolyI:C-mediated pro-inflammatory cytokine production in MoDC, notably, ssON treatment maintained an interferon response induced by IAV infection. Accordingly, RNAseq analyses revealed robust up-regulation of interferon-stimulated genes in IAV cultures treated with ssON. We next measured reduced IAV production in MoDC treated with ssON and found a length requirement for its anti-viral activity, which overlapped with its capacity to inhibit uptake of PolyI:C. Hence, in cases wherein an overreacting TLR3 activation contributes to IAV pathogenesis, ssON can reduce this signaling pathway. Furthermore, concomitant treatment with ssON and IAV infection in mice resulted in maintained weight and reduced viral load in the lungs. Therefore, extracellular ssON provides a mechanism for immune regulation of TLR3-mediated responses and suppression of IAV infection in vitro and in vivo in mice.
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| 15. |
- Sonkoly, Enikö, et al.
(författare)
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MicroRNAs : novel regulators involved in the pathogenesis of psoriasis?
- 2007
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 2:7
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in health and disease. Psoriasis is the most prevalent chronic inflammatory skin disease in adults, with a substantial negative impact on the patients' quality of life. Here we show for the first time that psoriasis-affected skin has a specific microRNA expression profile when compared with healthy human skin or with another chronic inflammatory skin disease, atopic eczema. Among the psoriasis-specific microRNAs, we identified leukocyte-derived microRNAs and one keratinocyte-derived microRNA, miR-203. In a panel of 21 different human organs and tissues, miR-203 showed a highly skin-specific expression profile. Among the cellular constituents of the skin, it was exclusively expressed by keratinocytes. The up-regulation of miR-203 in psoriatic plaques was concurrent with the down-regulation of an evolutionary conserved target of miR-203, suppressor of cytokine signaling 3 (SOCS-3), which is involved in inflammatory responses and keratinocyte functions. Our results suggest that microRNA deregulation is involved in the pathogenesis of psoriasis and contributes to the dysfunction of the cross talk between resident and infiltrating cells. Taken together, a new layer of regulatory mechanisms is involved in the pathogenesis of chronic inflammatory skin diseases.
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| 16. |
- Svedberg, Lena, 1958, et al.
(författare)
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Skin temperature in the extremities of healthy and neurologically impaired children.
- 2005
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Ingår i: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. - : Elsevier BV. - 1090-3798. ; 9:5, s. 347-54
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Tidskriftsartikel (refereegranskat)abstract
- Little emphasis has been accorded to peripheral skin temperature impairments in children with neurological disorders but attention has been paid to the significance of cold extremities (autonomic failure) for well-being and quality of life in adults stroke patients. Therefore, it seems important to investigate skin temperature in children with neurological disorder, especially when their communication is impaired. In the present study, we wanted to objectively verify any skin temperature differences between pre-school children with and without neurological disorders and also ascertain if any correlation existed between skin temperature and physical activity. Skin temperatures in 25 healthy children and 15 children with cerebral or spinal cord damages were assessed using infrared radiation. The temperatures were recorded on the palm and the dorsal surface of the hands and on the sole and dorsal surface of the feet three times at 15-minute intervals over 30min. A significant lower mean skin temperature in all measurement points was seen in non-walking children with cerebral damages compared to healthy controls. Also, the mean skin temperature was significantly lower in all foot measuring points in the children with cerebral damages that were unable to walk compared to those walking. In conclusion, as cold extremities may result in impaired well-being and hypothetically may be associated with other symptoms born by the child, further investigations of thermal dysfunction and autonomic function are of importance and treatment may be warranted.
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