| 1. |
- Andréasson, Per, 1963-
(författare)
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Emotional Empathy, Facial Reactions, and Facial Feedback
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human face has a fascinating capability to express emotions. The facial feedback hypothesis suggests that the human face not only expresses emotions but is also able to send feedback to the brain and modulate the ongoing emotional experience. It has furthermore been suggested that this feedback from the facial muscles could be involved in empathic reactions. This thesis explores the concept of emotional empathy and relates it to two aspects concerning activity in the facial muscles. First, do people high versus low in emotional empathy differ in regard to in what degree they spontaneously mimic emotional facial expressions? Second, is there any difference between people with high as compared to low emotional empathy in respect to how sensitive they are to feedback from their own facial muscles? Regarding the first question, people with high emotional empathy were found to spontaneously mimic pictures of emotional facial expressions while people with low emotional empathy were lacking this mimicking reaction. The answer to the second question is a bit more complicated. People with low emotional empathy were found to rate humorous films as funnier in a manipulated sulky facial expression than in a manipulated happy facial expression, whereas people with high emotional empathy did not react significantly. On the other hand, when the facial manipulations were a smile and a frown, people with low as well as high emotional empathy reacted in line with the facial feedback hypothesis. In conclusion, the experiments in the present thesis indicate that mimicking and feedback from the facial muscles may be involved in emotional contagion and thereby influence emotional empathic reactions. Thus, differences in emotional empathy may in part be accounted for by different degree of mimicking reactions and different emotional effects of feedback from the facial muscles.
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| 2. |
- Dorell, Åsa, et al.
(författare)
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Family Health Conversations have positive outcomes on families : A mixed method study
- 2017
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Ingår i: Open Nursing Journal. - : Bentham Open. - 1874-4346. ; :11, s. 14-25
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Tidskriftsartikel (refereegranskat)abstract
- Background: A Family Systems Nursing intervention, “Family Health Conversations” (FamHC) was conducted in order to strengthen the health of families having relatives at residential home for older people. Having a family member living in a residential home affects the entire family and can be hard to handle. Family members require encouraging and open communication support from nurse during and after relocation to a residential home.Objectives: The aims of this study were to evaluate the responses to and effects of the Family Health Conversations in families with a member living at a residential home for older people and to integrate the empirical results with a theoretical assumption upon which the intervention was based.Methods: A mixed method research design was used. The Swedish Health-Related Quality of Life Survey and the Family Hardiness Index were administered before and 6 months after the intervention. Qualitative data was collected by semi-structured interviews with each family 6 months post-intervention. The sample included families of residents, a total of 10 families comprising 22 family members.Result: Main finding was that FamHCs helped family members process their feelings about having a member living at a residential home and made it easier for them to deal with their own situations. FamHCs helped to ease their consciences, improve their emotional well-being, and change their beliefs about their own insufficiency and guilt. Seeing problems from a different perspective facilitated the families’ thinking in a new way.Conclusion: These findings showed that FamHC can be an important type of intervention to improve family functioning and enhance the emotional well-being.
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| 3. |
- Fritzson, Ingela, et al.
(författare)
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N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors
- 2011
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Ingår i: MedChemComm. - : Royal Society of Chemistry (RSC). - 2040-2511 .- 2040-2503. ; 2:9, s. 895-898
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Tidskriftsartikel (refereegranskat)abstract
- In our continuing program to develop Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors, a series of N-substituted salicylamides were synthesized and their ability to selectively inhibit PfDHODH was examined. The synthetic program was based on 2-hydroxy-N-(2-phenylethyl)benzamide (1) that weakly inhibits both PfDHODH and human DHODH (hDHODH). Structure activity relationships were examined for developing derivatives. Selective PfDHODH inhibitors with improved potency were obtained by introducing a 2,2-diphenylethyl substitution on the salicylamidic nitrogen. Biological activity of the most potent compounds was confirmed on parasite infected cells in vitro.
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| 4. |
- Klasson Sundin, Maria, 1961-
(författare)
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Barnets religionsfrihet – en villkorad rättighet? : En filosofisk undersökning utifrån FN:s barnkonvention
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation uses philosophical tools to examine the child’s right to freedom of religion within the context of the United Nations Convention on the Rights of the Child (CRC) and other international human rights instruments.Article 14 of the CRC establishes the right of the child to freedom of thought, conscience and religion. It also establishes the right of the child's parents to guide and support the child in its exercise of the right to freedom of religion, while adjusting this support according to the child's evolving capacities. The emphasis of the study is on how to understand the child as, on the one hand, agent and subject in the exercise of this right and, on the other, dependent on parental support and guidance. For this purpose, the theoretical underpinnings of the child’s right to freedom of religion are examined with a particular focus on the conceptualization of this right in relation to children. With the text of the CRC as a starting point, different theories on rights, autonomy and religion are analyzed in order to find those compatible with both aspects of Article 14: the child as agent and the child as dependent. Theories that demand fully developed cognitive abilities in order to be a moral agent and a rights holder are rejected, as are theories in which the parents are the sole decision-makers on the basis of their own view of what is in the child's interests. In the same way, conceptions of religion in purely cognitive terms, or not taking into account dimensions of practice and observance accessible to children, are rejected.The conclusion drawn from the analysis is that relational conceptualizations of rights and autonomy and multi-dimensional conceptualizations of religion are best served to include both aspects of the child's right to freedom of religion. In viewing all humans, adults and children alike, as both active agents and vulnerably dependent on others, these conceptualizations challenge traditional views on rights and autonomy, and modern views of religion. In the final chapter, aspects of these relational conceptions are put together into a relational, mutuality-oriented model of the child's right to freedom of religion.
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| 5. |
- Lundström, Emeli, et al.
(författare)
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HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 72:6, s. 1018-1025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES:Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients.METHODS:665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR.RESULTS: HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL—cardiolipin IgG and IgM, β2-glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04—while HLA-DRB1*13 was associated with IgG antibodies (β2-glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD.CONCLUSIONS:The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability.
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| 6. |
- Muth, Andreas, 1974, et al.
(författare)
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Nationellt vårdprogram för adrenala incidentalom - Programmet har harmoniserats med europeiska riktlinjer – ger förenklad handläggning av patienter.
- 2017
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 114
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Tidskriftsartikel (refereegranskat)abstract
- Swedish guidelines for the management of adrenal incidentalomas Adrenal incidentalomas are seen in about five percent of abdominal CT examinations, and in most cases represent non-hormone-producing adrenocortical adenomas, but hormone-producing or malignant lesions occur. Revised Swedish guidelines for the evaluation and management of adrenal incidentalomas based on recently published European guidelines are presented. The importance of a thorough radiological, clinical and biochemical initial evaluation is emphasized. Long-term biochemical follow-up is not recommended and use of CT contrast medium »washout« calculation is omitted. No radiological evaluation or follow-up indicated for adrenal incidentalomas <1 cm size. For patients with diagnosed lipid rich adenomas (≤ 10 HU) 1-4 cm in size no radiological follow-up is suggested after initial evaluation.
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| 7. |
- Pal, Kumar Bhaskar, et al.
(författare)
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Quinoline-galactose hybrids bind selectively with high affinity to a galectin-8 N-terminal domain
- 2018
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Ingår i: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 16:34, s. 6295-6305
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Tidskriftsartikel (refereegranskat)abstract
- Quinolines, indolizines, and coumarins are well known structural elements in many biologically active molecules. In this report, we have developed straightforward methods to incorporate quinoline, indolizine, and coumarin structures into galactoside derivatives under robust reaction conditions for the discovery of glycomimetic inhibitors of the galectin family of proteins that are involved in immunological and tumor-promoting biological processes. Evaluation of the quinoline, indolizine and coumarin-derivatised galactosides as inhibitors of the human galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9N, and 9C revealed quinoline derivatives that selectively bound galectin-8N, a galectin with key roles in lymphangiogenesis, tumor progression, and autophagy, with up to nearly 60-fold affinity improvements relative to methyl β-d-galactopyranoside. Molecular dynamics simulations proposed an interaction mode in which Arg59 had moved 2.5 Å and in which an inhibitor carboxylate and quinoline nitrogen formed structure-stabilizing water-mediated hydrogen bonds. The compounds were demonstrated to be non-toxic in an MTT assay with several breast cancer cell lines and one normal cell line. The improved affinity, selectivity, and low cytotoxicity suggest that the quinoline-galactoside derivatives provide an attractive starting point for the development of galectin-8N inhibitors potentially interfering with pathological lymphangiogenesis, autophagy, and tumor progression.
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| 8. |
- Pusa, Susanna, 1982-
(författare)
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Vägen mot implementering av familjecentrerad omvårdnad
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: När människor är inkluderade i varandras liv påverkar en förändring av livssituationen hos en person även de övriga personerna som står den nära. Det innebär att när en person drabbas av ohälsa eller sjukdom påverkas även personens familj. Familjens upplevelse av den situation som uppstår i samband med ohälsa kan dessutom negativt påverka familjemedlemmarnas medvetenhet om familjens tillgängliga styrkor och resurser, vilket i sin tur kan påverka familjers kamp för att återfå och bibehålla hälsa. Traditionellt sett har vården fokuserat på att erbjuda stöd på personnivå, och främst då till patienter. De senaste decennierna har dock en tendens uppmärksammats till ökad förståelse för att hela familjen behöver inkluderas i omvårdnaden. Att anamma ett familjecentrerat förhållningssätt – det vill säga, att se och möta familjen som en enhet och som ett system – har visat sig ha flera fördelar utifrån såväl patient- och familje- som sjuksköterskeperspektiv. Detta har medfört en efterfrågan på forskning om hur familjecentrerad omvårdnad kan läras ut och implementeras i den kliniska hälso- och sjukvården.Syfte: Det övergripande syftet med avhandlingen är att belysa erfarenheter av stöd från distriktssköterskor/sjuksköterskor till familjer i ordinärt boende, samt att utvärdera implementering av familjecentrerade samtal.Metod: Avhandlingen inkluderar tre studier med kvalitativ design och en studie med mixad-metod design. I delstudie I samlades data in genom tio fokusgruppintervjuer med 36 distriktssköterskor och analyserades sedan med en fenomenologisk hermeneutisk metod. Datainsamlingen för delstudie II bestod av ljudinspelade familjecentrerade samtal med sju familjer, samt sju avslutande brev riktade till familjerna som distriktssköterskorna/sjuksköterskorna skrev efter samtalen med familjerna. Familjesamtalen och breven analyserades med hjälp av kvalitativ innehållsanalys. I delstudie III analyserades individuella intervjuer med 21 distriktssköterskor/sjuksköterskor med kvalitativ innehållsanalys. Mixad metod användes i delstudie IV, där kvantitativa data från instrumentet Families’ Importance in Nursing Care – Nurses’ Attitudes (FINC-NA) integrerades med kvalitativa data från individuella intervjuer med 14 distriktssköterskor/sjuksköterskor.Resultat: Resultatet visar att distriktssköterskor/sjuksköterskor strävar efter att stödja familjer (I, IV) och att familjecentrerad omvårdnad i form av familjecentrerade samtal kan vara ett sätt att stöda familjer att dela med sig av sina upplevelser och känslor både inom familjen och med distriktssköterskan/ sjuksköterskan (II, IV). Det upplevda stödet från såväl familjen som distriktssköterskan/sjuksköterskan ansågs värdefullt för att bättre hantera situationen och framtiden (II). Distriktssköterskorna/sjuksköterskorna uppfattade den webbaserade utbildningen i familjecentrerad omvårdnad inklusive familjecentrerade samtal som överlag funktionell och välanpassad (III). Utbildningen med den påföljande implementeringen beskrevs bidra till ett förändrat förhållningssätt hos dem, där de tänkte och arbetade mer inkluderande och stödjande gentemot familjer, även när de inte utförde familjecentrerade samtal enligt den tänkta strukturen (III, IV). Utvärderingen av implementeringen av de familjecentrerade samtalen visade att införandet av familjecentrerade samtal fortgick även om de inte hade implementerats fullt ut som avsett. Acceptans och lämplighet utvärderades överlag positivt, dock framkom personliga, sociala och organisatoriska hinder, vilka påverkade genomförandet, användningen och metodtroheten (IV).Konklusion: Stöd från distriktssköterskor/sjuksköterskor till familjer är en omvårdnadshandling som förutsätter medveten omsorg i ett aktivt möte med familjen, där varje enskild person, men även familjen som enhet, behöver beaktas. Detta stöd för familjers hälsa kan ske genom familjecentrerad omvårdnad. En webbaserad utbildning för distriktssköterskor/sjuksköterskor i familjecentrerad omvårdnad och familjecentrerade samtal utgör ett adekvat steg i processen att implementera detta arbetssätt i den kliniska verksamheten. Sammanfattningsvis bidrar avhandlingen till kunskap om hur stödjande familjecentrerade samtal kan implementeras i klinisk verksamhet och vilka aspekter som kan påverka detta.
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| 9. |
- Rajput, Vishal Kumar, et al.
(författare)
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Galactose-amidine derivatives as selective antagonists of galectin-9
- 2016
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Ingår i: Canadian Journal of Chemistry. - : Canadian Science Publishing. - 0008-4042 .- 1480-3291. ; 94:11, s. 936-939
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Tidskriftsartikel (refereegranskat)abstract
- The family of galectin proteins involved in adhesion, growth regulation, immunity, and inflammatory events are important targets for development of small molecule antagonists. Here, N-sulfonyl amidine galactopyranoside derivatives obtained via a multicomponent reaction between galactose alkyne derivatives, sulfonyl azides, and amines were evaluated as antagonists of galectin-1,-2,-3,-4N (N-terminal domain),-4C (C-terminal domain),-8N,-9N, and-9C in a competitive fluorescence polarization assay. Highly selective compounds against galectin-9N with up to 30-fold improved affinity compared to the reference methyl β-d-galactopyranoside were identified. Molecular dynamics simulation suggested that the selectivity and affinity for galectin-9N originate from the N-sulfonyl amidine moieties forming tridentate hydrogen bonds to two asparagine side chains and one phenyl stacking edge-to-face to an arginine side chain. These selective galectin-9N antagonists are of significant value as chemical tools for studying galectin-9 biology and chemistry as well as possible starting structures for the discovery of galectin-9-targeting drugs influencing, e.g., immune regulation.
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| 10. |
- Salameh, Bader A., et al.
(författare)
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1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors
- 2010
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 18:14, s. 5367-5378
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Tidskriftsartikel (refereegranskat)abstract
- Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di-and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3. (C) 2010 Elsevier Ltd. All rights reserved.
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| 11. |
- Salomonsson, Emma, et al.
(författare)
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Monovalent Interactions of Galectin-1
- 2010
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 49:44, s. 9518-9532
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-1, beta-galactoside binding lectin involved in immunoregulation and cancer, binds natural and many synthetic multivalent glycoconjugates with an apparent glycoside cluster effect, that is, affinity above and beyond what would be expected from the concentration of the determinant sugar. Here we have analyzed the mechanism of such cluster effects in solution at physiological concentration using a fluorescence anisotropy assay with a novel fluorescent high-affinity galectin-1 binding probe. The interaction of native dimeric and monomeric mutants of rat and human galectin-1 with mono- and divalent small molecules, fetuin, asialofetuin, and human serum glycoproteins was analyzed. Surprisingly, high-affinity binding did not depend much on the dimeric state of galectin-1 and thus is due mainly to monomeric interactions of a single carbohydrate recognition domain. The mechanism for this is unknown, but one possibility includes additional interactions that high-affinity ligands make with an extended binding site on the carbohydrate recognition domain, It follows that such weak additional interactions must be important for the biological function of galectin-1 and also for the design of galectin-1 inhibitors.
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| 12. |
- Salomonsson, Emma, et al.
(författare)
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Mutational tuning of galectin-3 specificity and biological function.
- 2010
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 285, s. 35079-35091
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Tidskriftsartikel (refereegranskat)abstract
- Galectins are defined by a conserved beta-galactoside binding site, which has been linked to many of their important functions in e.g. cell adhesion, signaling and intracellular trafficking. Weak adjacent sites may enhance or decrease affinity for natural beta-galactoside containing glycoconjugates, but little is known about the biological role of this modulation of affinity (fine specificity). We have now produced 10 mutants of human galectin-3, with changes in these adjacent sites, which have altered carbohydrate-binding fine specificity but which retain the basic beta-galactoside binding activity as show by glycan-array binding and a solution-based fluorescence anisotropy assay. Each mutant was also tested in two biological assays to provide a correlation between fine specificity and function. Galectin-3 R186S, which has selectively lost affinity for LacNAc, a disaccharide moiety commonly found on glycoprotein glycans, has lost the ability to activate neutrophil leukocytes and intracellular targeting into vesicles. K176L has increased affinity for beta-galactosides substituted with GlcNAcbeta1-3 as found in poly-N-acetyllactosaminoglycans, and increased potency to activate neutrophil leukocytes, even though it has lost other aspects of galectin-3 fine specificity. G182A has altered carbohydrate-binding fine specificity and altered intracellular targeting into vesicles, a possible link to the intracellular galectin-3-mediated anti-apoptotic effect known to be lost by this mutant. Finally, the mutants have helped to define the differences in fine specificity shown by Xenopus, mouse and human galectin-3 and as such, evidence for adaptive change during evolution.
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| 13. |
- Siegbahn, Anna, et al.
(författare)
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Rules for priming and inhibition of glycosaminoglycan biosynthesis; probing the beta 4GalT7 active site
- 2014
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 5:9, s. 3501-3508
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Tidskriftsartikel (refereegranskat)abstract
- beta-1,4-Gatactosyltransferase 7 (beta 4GalT7) is an essential enzyme in the biosynthesis of glycosaminoglycan (GAG) chains of proteoglycans (PGs). Mammalian cells produce PGs, which are involved in biological processes such as cell growth and differentiation. The PGs consist of a core protein, with one or several GAG chains attached. Both the structure of the PGs and the GAG chains, and the expression of the enzymes involved in their biosynthesis and degradation, vary between normal cells and tumor cells. The biosynthesis of GAG chains is initiated by xylosylation of a serine residue of the core protein, followed by galactosylation by beta 4GalT7. The biosynthesis can also be initiated by exogenously added beta-D-xylopyranosides with hydrophobic aglycons, which thus can act as acceptor substrates for beta 4GalT7. To determine the structural requirements for beta 4GalT7 activity, we have cloned and expressed the enzyme and designed a focused library of 2-naphthyl beta-D-xylopyranosides with modifications of the xylose moiety. Based on enzymatic studies, that is galactosylation and its inhibition, conformational analysis and molecular modeling using the crystal structure, we propose that the binding pocket of beta 4GalT7 is very narrow, with a precise set of important hydrogen bonds. Xylose appears to be the optimal acceptor substrate for galactosylation by beta 4GalT7. However, we show that modifications of the xylose moiety of the beta-D-xylopyranosides can render inhibitors of galactosylation. Such compounds will be valuable tools for the exploration of GAG and PG biosynthesis and a starting point for development of anti-tumor agents.
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| 14. |
- Singh, Birendra, et al.
(författare)
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Haemophilus influenzae surface fibril (Hsf) is a unique twisted hairpin-like trimeric autotransporter
- 2015
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Ingår i: International Journal of Medical Microbiology. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 305:1, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- The Haemophilus surface fibril (Hsf) is an extraordinary large (2413 amino acids) trimeric autotransporter, present in all encapsulated Haemophilus influenzae. It contributes to virulence by directly functioning as an adhesin. Furthermore, Hsf recruits the host factor vitronectin thereby inhibiting the host innate immune response resulting in enhanced survival in serum. Here we observed by electron microscopy that Hsf appears as an 100. nm long fibril at the bacterial surface albeit the length is approximately 200. nm according to a bioinformatics based model. To unveil this discrepancy, we denaturated Hsf at the surface of Hib by using guanidine hydrochloride (GuHCl). Partial denaturation induced in the presence of GuHCl unfolded the Hsf molecules, and resulted in an increased length of fibres in comparison to the native trimeric form. Importantly, our findings were also verified by E. coli expressing Hsf at its surface. In addition, a set of Hsf-specific peptide antibodies also indicated that the N-terminal of Hsf is located near the C-terminal at the base of the fibril. Taken together, our results demonstrated that Hsf is not a straight molecule but is folded and doubled over. This is the first report that provides the unique structural features of the trimeric autotransporter Hsf.
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| 15. |
- Sundin, Maria, 1965, et al.
(författare)
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Exoplaneter
- 2018
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Ingår i: Svenska Matematiker Samfundets Bulletin. ; :Februari 2018, s. 20-24
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 16. |
- Svenungsson, Elisabet, et al.
(författare)
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A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 69:5, s. 834-840
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE. Methods Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped. Results The STAT4 risk allele was more frequent in patients with SLE with previous arterial events (combined OR (ORc)=1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The association was mainly attributable to an accumulation of the risk allele among patients with ICVD (ORc=2.3, CI 1.6 to 3.3). There was no association with IHD or VTE. The presence of two or more aPLs was associated with the risk allele (ORc=1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression analyses treatment for hypertension, at least one STAT4 risk allele, older age, IgG anti-cardiolipin antibodies and longer SLE duration remained independently associated with previous ICVD (p≤0.02 for all). Conclusion Patients with SLE with the STAT4 risk allele had a strikingly increased risk of ICVD, comparable in magnitude to that of hypertension. The results imply that a genetic predisposition is an important and previously unrecognised risk factor for ICVD in SLE, and that aPLs may be one underlying mechanism.
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| 17. |
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