| 11. |
- Montgomery, Scott, et al.
(författare)
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Hospital admission due to infections in multiple sclerosis patients
- 2013
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Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 20:8, s. 1153-1160
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Multiple sclerosis (MS) patients are at increased infection risk. Here the influences of susceptibility, severity and surveillance bias on infection-related hospital admission are assessed.Methods: Swedish registers identified 20 276 patients with MS, matched with 203 951 people from the general population without MS. Risk of first hospital admission for infection and mortality over 36 years was estimated by Poisson regression.Results: Multiple sclerosis was associated with an increased hospital admission risk for all infections, with an adjusted relative risk (and 95% confidence interval) of 4.26 (4.13-4.40). A proportion of this raised risk was probably due to surveillance and referral bias, although a raised risk remained when MS was compared with other immune-mediated diseases. The 1-month mortality rate following hospital admission for infection was higher in MS patients than in the comparison cohort, with a relative risk of 4.69 (4.21-5.22). There was no clear temporal trend in the results, and risks were higher in males and varied by MS phenotype.Conclusions: Higher hospital admission rates among MS patients for infection are likely to be due to a combination of surveillance bias, cautious medical management and greater susceptibility to severe infections. MS-related functional limitations may increase infection risk and this should be considered in MS management.
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| 12. |
- Lundberg, Peter, et al.
(författare)
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Kvantifiering av leversteatos: diagnostisk utvärdering av protonmagnetresonansspektroskopi jämfört med histologiska metoder
- 2016
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Konferensbidrag (refereegranskat)abstract
- BakgrundLeversteatos är den vanligaste manifestationen av leversjukdom i västvärlden. Leverbiopsi med semikvantitativ histologisk gradering är referensmetod vid gradering av leversteatos. Med protonmagnetsresonansspektroskopi (1H-MRS), en metod som föreslagits ersätta leverbiopsi för värdering av steatos, kan leverns innehåll av triglycerider mätas icke-invasivt. Triglyceridinnehåll >5,00 % används ofta som ett diagnostiskt kriterium för leversteatos vid undersökning med 1H-MRS. Syftet med studien var att jämföra 1H-MRS med semikvantitativ histologisk steatosgradering och kvantitativ histologisk steatosmätning.MetodPatienter remitterade för utredning av förhöjda leverenzymer in-kluderades i studien. Samtliga patienter genomgick klinisk undersökning, laboratorieprovtagning samt 1H-MRS direkt följd av leverbiopsi. För konventionell histologisk semikvantitativ gradering av steatos användes kriterierna utarbetade av Brunt och medarbetare. Kvantitativ mätning av fett i biopsierna utfördes genom att med hjälp av stereologisk punkträkning (SPC) mäta andelen av ytan som innehöll fettvakuoler.ResultatI studien inkluderades 94 patienter, varav 37 hade icke-alkoholor-sakad fettleversjukdom (NAFLD), 49 hade andra leversjukdomar och 8 hade normal leverbiopsi. En stark korrelation noterades mel-lan 1H-MRS och SPC (r=0,92, p<0,0001; к=0.82). Korrelationen mellan 1H-MRS och Brunts kriterier (к=0.26) samt mellan SPC och Brunts kriterier (к=0.38) var betydligt sämre. När patologens gradering (Brunts kriterier) användes som referensmetod för diag-nos av leversteatos så hade alla patienter med triglyceridinnehåll >5,00 % mätt med 1H-MRS steatos (specificitet 100 %). Emellertid hade 22 av 69 patienter med triglyceridinnehåll ≤5,00 % också le-versteatos enligt Brunts kriterier (sensitivitet 53 %). Motsvarande siffror när man använde gränsvärdet 3,02 % var sensitivitet 79 % och specificitet 100 %. Vid ytterligare reduktion av gränsvärdet för triglyceridinnehåll till 2,00 % ökade sensitiviteten till 87 % med upprätthållande av hög specificitet (94 %).Slutsats1H-MRS och SPC uppvisade en mycket hög korrelation vid kvantifiering av leversteatos. SPC borde därför föredras framför Brunts kriterier när noggrann histologisk kvantifiering av leversteatos är önskvärd. Många patienter kan ha histologisk leversteatos trots triglyceridinnehåll ≤5,00 % mätt med 1H-MRS. Gränsvärdet för diagnostisering av leversteatos med 1H-MRS bör därför reduceras.
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| 13. |
- Hellström Ängerud, Karin, et al.
(författare)
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Differences in symptoms in relation to myocardial infarction.
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: In myocardial infarction (MI) rapid diagnosis and treatment is crucial for the prognosis. Previous research has found that symptom presentation influence pre hospital delay times but studies about differences in MI symptoms between patients with ST-elevation myocardial infarction (STEMI) and non ST-elevation myocardial infarction (NSTEMI) are sparse and inconclusive. To enhance the understanding of symptom presentation in regard to MI type, we aimed to describe symptoms in relation to MI type and to find predictors of STEMI versus NSTEMI in patients with MI.Methods: Patients with MI (n=694) from the SymTime study were included. SymTime was a multicentre cross-sectional study of symptoms and actions in the prehospital phase of MI and data were collected using a previously validated questionnaire administered to MI patients within 24 h of admission to hospital.Results: Patients with STEMI were younger, more often men and smokers. Patients with NSTEMI were more likely to have a history of hypertension, MI and stroke. Chest pain was the most common symptom in both groups. Pain, discomfort, or pressure located in the jaw or teeth, vertigo/pre-syncope, cold sweat and nausea/vomiting were significantly more frequent in patients with STEMI (Table 1). In a multivariate logistic regression model patients with STEMI were more likely to present with cold sweat (OR 4.13, 95% CI 2.71–6.29) jaw pain (OR 2.14, 95% CI 1.02–4.50), and nausea (OR 2.01, 95% CI 1.20–3.33), and less likely to have a history of stroke (OR 0.35, 95% CI 0.15–0.84), fluctuating symptoms (OR 0.54, 95% CI 0.36–0.83) and anxiety (OR 0.54, 95% CI 0.32–0.92) compared to patients with NSTEMI.Conclusion: Patients with STEMI differed significantly from those with NSTEMI regarding symptom presentation. This knowledge is important for health care personnel to recognize symptoms alarming for STEMI when evaluating patients with MI symptoms.
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| 14. |
- Eriksson, Catharina, 1955-, et al.
(författare)
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Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus
- 2003
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 12:10, s. 766-774
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Tidskriftsartikel (refereegranskat)abstract
- The expression of chemokine receptors on T-cells and chemokine levels in the blood was studied in 23 patients with SLE (ACR criteria), seven patients with rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002, respectively). The decrease of CXCR5 was confined to SLE patients with inactive disease (SLEDAI < 6) compared with active disease (SLEDAI &GE; 6) and controls. CXCR2 and CCR1 were increased in patients with active SLE compared with patients with inactive disease (P = 0.001 and P = 0.01, respectively) and with controls ( P = 0.02 and P = 0.053, respectively). The levels of the chemokines MIP-1β MCP-1, SDF-1α, IP-10 and RANTES were significantly elevated in SLE patients compared with controls. Patients with renal involvement had increased surface expression of CXCR3 and CCR3 (P = 0.04 in both) and a lower level of soluble IP-10 compared with patients without renal disease (P = 0.025) and compared with controls (P = 0.001). The ratio between CCR5 and CCR3 was significantly increased in RA patients compared with SLE patients and controls supporting a Th1 overweight in RA. In conclusion, patients with SLE showed abnormal T-cell expression of several chemokine receptors and levels of soluble chemokines in their plasma/ serum.
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| 15. |
- Eriksson, Catharina, 1955-, et al.
(författare)
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Autoantibodies predate the onset of Systemic Lupus Erythematosus in northern Sweden
- 2011
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 13:1, s. R30-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Autoantibodies have a central role in systemic lupus erythematosus (SLE). The presence of autoantibodies preceding disease onset by years has been reported both in patients with SLE and those with rheumatoid arthritis, suggesting a gradual development of these diseases. To identify autoantibodies in a Northern European population predating the onset of symptoms of SLE and their relationship to presenting symptoms.METHODS: The register of patients fulfilling the American College of Rheumatology (ACR) criteria for SLE and with a given date for the onset of symptoms was co-analysed with the register of the Medical Biobank, Umea, Sweden. Thirty-eight patients were identified as having donated blood samples prior to symptom onset. A nested case-control study (1:4) was performed with 152 age- and sex-matched controls identified from within the Biobank register. Antibodies against anti- Sjogren's syndrome antigen A (Ro/SSA) (60 and 52 kDa), anti- Sjogren's syndrome antigen B (La/SSB), anti-Smith antibody (Sm), ribonucleoprotein (RNP), scleroderma-70 (Scl-70), anti- histidyl-tRNA synthetase antibody (Jo-1), double-stranded DNA (dsDNA); Centromere protein B and histones were analysed using the anti-nuclear antibody test II (ANA-II) Plus Test System (Athena Multi-Lyte(R)) on a Bio-Plex Array Reader (Luminex200). ANA were analysed using indirect immunofluorescence on Human Epidermal cells-2 (HEp2-cells) at a sample dilution of 1:100.RESULTS: Autoantibodies against nuclear antigens were detected 5.6 (+/- 4.7; mean +/- SD) years before the onset of symptoms and 8.7 (+/- 5.6) years before diagnosis in 63% of the individuals who subsequently developed SLE. The sensitivity (45.7%) was highest for ANA with a specificity of 95%, followed by anti-dsDNA and anti-Ro/SSA antibodies both with sensitivities of 20.0% at specificities of 98.7% and 97.4%, respectively. The odds ratio (OR) for anti-dsDNA predicting disease was 18.13 (CI 95%; 3.58-91.84), and for ANA 11.5 (CI 95%; 4.54-28.87). Anti-Ro/SSA antibodies appeared first, 6.6 (+/- 2.5) years prior to symptom onset. The mean number of autoantibodies in pre-diseased individuals was 1.4 and after disease onset 3.1 (P< 0.0005). The time predating disease was shorter, and the number of autoantibodies greater, in those individuals with serositis as a presenting symptom in comparison to those with arthritis and skin manifestations.CONCLUSIONS: Autoantibodies against nuclear antigens were detected in individuals developing SLE several years before the onset of symptoms and diagnosis. The most sensitive autoantibodies were ANA, Ro/SSA and dsDNA, with the highest predictive OR for anti-dsDNA antibodies. The first autoantibodies detected were anti-Ro/SSA.
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| 16. |
- Eriksson, Catharina, 1955-, et al.
(författare)
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Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha
- 2005
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 64:3, s. 403-407
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Tidskriftsartikel (refereegranskat)abstract
- Background: Research on autoantibody formation in patients treated with TNFα inhibitors has produced contradictory results. Objective: To study the prevalence of autoantibodies in patients with rheumatoid arthritis treated with the TNFα inhibitor infliximab. Methods: 53 patients (48 female, 11 male) treated with infliximab for rheumatoid arthritis were followed for autoantibody production before treatment and after 14, 30, and 54 weeks. Six patients treated with etanercept were studied for comparison. The analyses included antibodies against nuclear antigens (ANA), extractable nuclear antigens, double stranded (ds)DNA (by ELISA, IIF on Crithidia luciliae for IgM and IgG, and Farr assay), nucleosomes, cardiolipin, smooth muscle, mitochondria, proteinase 3, and myeloperoxidase antigens. Results: The number of patients treated with infliximab who developed antibodies against dsDNA of both IgG and IgM class (tested by IIF) increased significantly. The prevalence of patients positive for IgG class increased to 66% at 30 weeks and 45% at 54 weeks, and of IgM class to 85% and 70%, respectively. The titre and number of patients expressing antibodies against nucleosomes and ANA also increased significantly. The number of rheumatoid factor or anticardiolipin positive patients was stable and there was no increase in antibodies against the other antigens. A lupus-like syndrome was seen in one patient. No patient treated with etanercept developed any of these autoantibodies. Conclusions: Patients treated with infliximab may develop anti-dsDNA antibodies of both IgM and IgG class, anti-nucleosome antibodies, and ANA, with a gradual increase until 30 weeks.
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| 17. |
- Eriksson, Catharina, 1955-
(författare)
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Immunological mechanisms in systemic autoimmunity : autoantibodies and chemokines in systemic lupus erythematosus and during treatment with TNF inhibitors in rheumatoid arthritis
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that, without powerful treatment, may lead to irreversible joint damage. During the past decade, anti-cytokine therapy has become available, e.g., infliximab, a chimeric antibody targeting the pro-inflammatory cytokine TNF that has a central role in the inflammatory process in RA patients. Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that may affect all organs and is characterized by a massive antibody production. Chemokines, chemokine receptors and lipoprotein receptor-related protein 1(CD91) are regulators of inflammation in autoimmune diseases and T-cell migration. Objectives. The aim of this study was to get a deeper understanding how TNF blocking treatment influences inflammatory mechanisms and autoantibody formation in RA with special reference to similarities and differences with SLE. Methods. In patients with RA treated with anti-TNF, and in SLE patients (ACR criteria) clinical evaluation was performed and blood samples analyzed. Autoantibodies were analyzed using indirect immunofluorescence, ELISA and multiplex flow cytometry in samples from anti-TNF treated RA patients (n=59) followed longitudinally for 54 weeks, in pre-diseased samples from SLE patients (n=38) and matched population-based controls (n=152). T-cell expression of chemokine receptors and CD91 was analyzed by flow cytometry, whilst serum levels of chemokines were determined using ELISA in anti-TNF treated RA-patients (n=24) followed longitudinally (30 weeks), and cross-sectionally in SLE-patients (n=23). Expression of mRNA for chemokines was analyzed in T-cells from SLE-patients (n=10) using PCR. Results. After treatment with infliximab, RA patients produced ANA, anti-dsDNA and anti-nucleosome antibodies, but not anti-ENA antibodies. Although these antibodies are considered typical for SLE only one patient developed a transient lupus-syndrome. Antibodies against cell nuclear antigens, including ENA, were detected several years before the first clinical symptom of SLE; anti-SSA was the earliest detectable antibody. In RA-patients before infliximab treatment, the T-cell expression of several chemokine receptors was elevated compared with healthy controls. In contrast, only one soluble chemokine, IP-10 was elevated. After treatment the levels of soluble MIP-1β, MCP-1 and IP-10, and the T-cell expression of CCR2 were decreased. In SLE-patients MIP-1β, MCP-1, SDF-1, IP-10 and RANTES in blood were elevated, whilst expression of CXCR5 and CCR6 on T-cells was lower than in healthy controls. T-cell expression of CXCR2 and CCR1 was elevated in active disease (measured as SLEDAI index), whereas the CXCR5 and CCR2 expression was lower in inactive SLE. In SLE patients with nephritis IP-10 was lower and T-cell expression of CXCR3 and CCR3 elevated compared with patients without nephritis. The expression of CD91 was higher on T-cells from patients not responsive to infliximab treatment compared with responders. Conclusion. These findings indicate that anti-TNF (infliximab) treatment in RA-patients has a major impact on the production of autoantibodies and chemokines. The autoantibody profile in infliximab-treated patients was similar to that predating disease onset in SLE patients with the exception of anti-ENA being detectable in SLE, but the development of lupus-syndromes was rare. The expression of CD91 on T-cells may predict responsiveness to infliximab. The expression of chemokine receptors in SLE- patients seemed to be related to disease activity. Anti-nuclear antibodies were detectable years before clinical disease onset in patients who developed SLE suggesting a gradual pathogenic process.
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| 18. |
- Eriksson, Catharina, 1955-, et al.
(författare)
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T-cell expression of CD91 : a marker of unresponsiveness to anti-TNF therapy in rheumatoid arthritis
- 2010
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 118:11, s. 837-845
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the expression of thrombospondin-1 (TSP-1) and its receptors, lipoprotein receptor-related protein/cluster of differentiation (CD)91, calreticulin (CRT), and CD47, on T cells and monocytes from patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) therapy. The surface expression of CD91 and associated components on CD3- and CD14-positive cells was examined using flow cytometry in 12 patients with established RA before and after beginning therapy and compared with that of 9 healthy controls and 12 patients with early RA treated with conventional therapies. CD3-positive cells from anti-TNF non-responders showed significantly greater expression of CD91 expression than those from responders (p<0.05) after 6 weeks and when all measurements were pooled (p<0.001). CD91 expression on CD3-positive cells from non-responders to other therapies was at the same level as in healthy controls. In contrast, CD14-positive cells showed no differences in CD91 expression between patients and controls or between responders and non-responders to anti-TNF therapy. The expression of TSP-1, CRT, and CD47 showed no differences between responders and non-responders. The results suggest T-lymphocyte expression of CD91 to be a biomarker that signifies unresponsiveness to anti-TNF therapy in patients with RA and may be used to identify potential responders and non-responders.
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| 19. |
- Strålberg, Fredrik, et al.
(författare)
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Inhibition of lipopolysaccharide-induced osteoclast formation and bone resorption in vitro and in vivo by cysteine proteinase inhibitors
- 2017
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Ingår i: Journal of Leukocyte Biology. - : FEDERATION AMER SOC EXP BIOL. - 0741-5400 .- 1938-3673. ; 101:5, s. 1233-1243
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation-induced bone destruction is a major treatment target in many inflammatory skeletal diseases. The aim of this study was to investigate if the cysteine proteinase inhibitors cystatin C, fungal cysteine proteinase inhibitor (E-64), and N-benzyloxycarbonyl-arginylleucyl-valyl-glycyl-diazomethane acetate (Z-RLVG-CHN2) can inhibit LPS-induced osteoclast formation. Mouse bone marrow macrophages (BMMs) were isolated and primed with receptor activator of NF-kappa B ligand (RANKL) for 24 h, followed by stimulation with LPS, with and without inhibitors. Adult mice were injected locally with LPS and then treated with E-64 and osteoclast formation assessed by the number of cathepsin K+ multinucleated cells. Cystatin C inhibited LPS-induced osteoclast formation time and concentration dependently (IC50 = 0.3 mu M). The effect was associated with decreased mRNA and protein expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K and of the osteoclastogenic transcription factors c-Fos and NFATc1. LPS-induced osteoclast formation on bone slices was also inhibited by cystatin C, resulting in decreased pit formation and release of bone matrix proteins. Similar data were obtained with E-64 and Z-RLVG-CHN2. Cystatin C was internalized in BMMs stimulated by LPS but not in unstimulated BMMs. Osteoclast formation induced by LPS was dependent on TNF-alpha, and the 3 inhibitors abolished LPS-induced TNF superfamily 2 (gene encoding TNF-alpha; Tnfsf2) mRNA expression without affecting Il1b, Il6, or oncostatin M (Osm) expression. Formation of osteoclasts in the skull bones after local LPS stimulation was inhibited by E-64. It is concluded that cysteine proteinase inhibitors effectively inhibit LPS-induced osteoclast formation in vivo and in vitro by inhibition of TNF-alpha expression. The targeting of cysteine proteinases might represent a novel treatment modality for prevention of inflammatory bone loss. RAHAMSON M, 1988, FEBS LETTERS, V236, P14 RAHAMSON M, 1990, BIOCHEMICAL JOURNAL, V268, P287
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| 20. |
- Fan, Yue, et al.
(författare)
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Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations.METHODS: Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies.RESULTS: We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype.CONCLUSIONS: Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.
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