| 1. |
- Tarkowski, Andrej, 1951, et al.
(författare)
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Current status of pathogenetic mechanisms in staphylococcal arthritis.
- 2002
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Ingår i: FEMS microbiology letters. - 0378-1097. ; 217:2, s. 125-32
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Forskningsöversikt (refereegranskat)abstract
- Interactions between staphylococci and the joint tissues of the host lead typically to rapidly progressing and highly destructive processes. Staphylococci possess a vast arsenal of components and products that contribute to the pathogenesis of joint infection. Occasionally these compounds have overlapping activities and act either in concert or alone. Host responsiveness to staphylococcal infection displays an even more complex pattern. Most of the cells and molecules that participate in the innate immune system protect the host against bacteria. However, the staphylococci have developed systems that counteract endogenous protective mechanisms. Interestingly, certain cells and molecules of the acquired immune system potentiate the severity of infection by triggering exaggerated responses to the staphylococcal danger signals. This review deals with the intricate host-bacterium interactions that occur during experimental septic arthritis, and outlines potential preventive and treatment modalities.
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| 2. |
- Aldridge, Jonathan, et al.
(författare)
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Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis.
- 2022
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:3
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with CTLA-4Ig blocks T cell activation and is clinically effective in rheumatoid arthritis (RA). However, it is unknown if specific CD4+ T cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4+ T cells in patients with untreated early RA (eRA).This study included 60 patients with untreated eRA from a larger randomised trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n = 17), anti-IL6 receptor (tocilizumab, n = 21) or anti-TNF (certolizumab-pegol, n = 22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI ≤ 2.8) at week 24. Proportions of 12 CD4+ T cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24 weeks of treatment.In patients treated with CTLA-4Ig, the proportions of PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline predicted CDAI remission at week 24. CD4+ T cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24 weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1+T follicular helper (TFh) cells.These findings indicate that circulating proportions PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.
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| 3. |
- Aldridge, Jonathan, et al.
(författare)
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T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3(+)Th2 phenotype
- 2020
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The majority of CD4(+)T helper (Th) cells found in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) express CXCR3, a receptor associated with Th1 cells. In blood, subsets of Th2 and Th17 cells also express CXCR3, but it is unknown if these cells are present in RA SF or how cytokines from these subsets affect cytokine/chemokine secretion by fibroblast-like synoviocytes (FLS) from patients with RA. Methods We examined the proportions of Th1, Th2, CXCR3(+)Th2, Th17, CXCR3(+)Th17, Th1Th17, peripheral T helper (TPh) and T follicular helper (TFh) cells in paired SF and blood, as well as the phenotype of TPh and TFh cells in RA SF (n = 8), by the use of flow cytometry. We also examined the cytokine/chemokine profile in paired SF and plasma (n = 8) and in culture supernatants of FLS from patients with chronic RA (n = 7) stimulated with Th-associated cytokines, by the use of cytometric bead arrays and ELISA. Cytokine receptor expression in FLS (n = 3) were assessed by the use of RNA sequencing and qPCR. Results The proportions of Th1 and CXCR3(+)Th2 cells were higher in SF than in blood (P < 0.05). TPh and PD-1(high)TFh in RA SF were primarily of a Th1 and a CXCR3(+)Th2 phenotype. Moreover, the levels of CXCL9, CXCL10, CCL20, CCL2, CXCL8, IL-6 and IL-10 were higher in SF than in plasma (P < 0.05). Lastly, IL-4, IL-13 and IL-17A induced RA FLS to secrete proinflammatory IL-6, CCL2, CXCL1 and CXCL8, while IFN gamma mainly induced CXCL10. Conclusion These findings indicate that not only Th1 but also CXCR3(+)Th2 cells may have a pathogenic role in RA synovial inflammation.
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| 4. |
- Bärebring, Linnea, et al.
(författare)
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Poor dietary quality is associated with increased inflammation in Swedish patients with rheumatoid arthritis
- 2018
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to study whether dietary quality was associated with disease activity and inflammation among patients with rheumatoid arthritis (RA). This cross-sectional analysis included 66 Swedish participants, who each completed a food frequency questionnaire (FFQ) at screening. Food intake was scored by a dietary quality index created by the Swedish National Food Agency. Disease activity was measured as Disease Activity Score 28 (DAS28), based on erythrocyte sedimentation rate (ESR), a patient administered visual analogue scale of perceived global health and the number of tender and swollen joints out of 28 examined. Inflammation was measured as ESR and C-reactive protein (hs-CRP). Associations between dietary quality, disease activity and inflammation were evaluated using multivariable linear regression analysis. High dietary quality (high intake of fish, shellfish, whole grain, fruit and vegetables and low intake of sausages and sweets) was not related to DAS28 (B = −0.02, p = 0.787). However, dietary quality was significantly negatively associated with hs-CRP (B = −0.6, p = 0.044) and ESR (B = −2.4, p = 0.002) after adjusting for body mass index, age, education, smoking and gender. Both hs-CRP and ESR decreased with increasing dietary quality. In conclusion, among patients with RA, high dietary quality was associated with reduced inflammation but not with disease activity.
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| 5. |
- Henningsson, Louise, 1979, et al.
(författare)
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Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a chronic destructive autoimmune disease characterised by periods of flare and remission. Today’s treatment is based on continuous immunosuppression irrespective of the patient’s inflammatory status. When the disease is in remission the therapy is withdrawn but withdrawal attempts often results in inflammatory flares, and re-start of the therapy is commenced when the inflammation again is prominent which leads both to suffering and increased risk of tissue destruction. An attractive alternative treatment would provide a disease-regulated therapy that offers increased anti-inflammatory effect during flares and is inactive during periods of remission. To explore this concept we expressed the immunoregulatory cytokine interleukin (IL)-10 gene under the control of an inflammation dependent promoter in a mouse model of RA - collagen type II (CII) induced arthritis (CIA). Haematopoetic stem cells (HSCs) were transduced with lentiviral particles encoding the IL-10 gene (LNT-IL-10), or a green fluorescence protein (GFP) as control gene (LNT-GFP), driven by the inflammation-dependent IL-1/IL-6 promoter. Twelve weeks after transplantation of transduced HSCs into DBA/1 mice, CIA was induced. We found that LNT-IL-10 mice developed a reduced severity of arthritis compared to controls. The LNT-IL-10 mice exhibited both increased mRNA expression levels of IL-10 as well as increased amount of IL-10 produced by B cells and non-B APCs locally in the lymph nodes compared to controls. These findings were accompanied by increased mRNA expression of the IL-10 induced suppressor of cytokine signalling 1 (SOCS1) in lymph nodes and a decrease in the serum protein levels of IL-6. We also found a decrease in both frequency and number of B cells and serum levels of anti-CII antibodies. Thus, inflammation-dependent IL-10 therapy suppresses experimental autoimmune arthritis and is a promising candidate in the development of novel treatments for RA.
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| 6. |
- Hulander, Erik, et al.
(författare)
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Diet intervention improves cardiovascular profile in patients with rheumatoid arthritis: results from the randomized controlled cross-over trial ADIRA.
- 2021
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Ingår i: Nutrition journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- The chronic inflammation in patients with rheumatoid arthritis (RA) increases the risk for cardiovascular diseases (CVD). The contribution of diet as a risk factor for CVD among these patients is however not fully understood. The aim of this study is to investigate if a proposed anti-inflammatory diet improves cardiovascular profile in weight stable patients with RA.Patients (n = 50) with RA were included in a cross-over trial. They were randomized to either a diet rich in whole grain, fatty fish, nuts, vegetables and fruit and supplemented with probiotics, or a control diet resembling average nutritional intake in Sweden, for ten weeks. After a 4-month washout they switched diet. Participants received food bags and dietary guidelines. Primary outcome was triglyceride (TG) concentration. Secondary outcomes were total-, high density lipoprotein- (HDL) and low density lipoprotein- (LDL) cholesterol, Apolipoprotein-B100 and -A1, lipoprotein composition, plasma phospholipid fatty acids and blood pressure.Forty-seven patients completed at least one period and they remained weight stable. There was a significant between-dietary treatment effect in TG and HDL-cholesterol concentration in favor of intervention (p = 0.007 and p = 0.049, respectively). Likewise, Apolipoprotein-B100/A1 ratio shifted toward a less atherogenic profile in favor of the intervention (p = 0.007). Plasma fatty acids increased in polyunsaturated- and decreased in monounsaturated- and saturated fatty acids between diet periods in favor of the intervention period.Blood lipid profile improved indicating cardioprotective effects from an anti-inflammatory dietary intervention in patients with RA.This trial is registered at ClinicalTrials.gov as NCT02941055 .
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| 7. |
- Hulander, Erik, et al.
(författare)
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Improvements in Body Composition after a Proposed Anti-Inflammatory Diet Are Modified by Employment Status in Weight-Stable Patients with Rheumatoid Arthritis, a Randomized Controlled Crossover Trial
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid Arthritis (RA) is an autoimmune disease affecting peripheral joints. Chronic activation of inflammatory pathways results in decreased function and the development of comorbidities, such as loss of lean mass while retaining total body mass. The objective of this report was to assess whether dietary manipulation affects body composition in patients with RA as a secondary outcome. Fifty patients were included in a randomized controlled crossover trial testing a proposed anti-inflammatory Mediterranean-style diet compared to a Western diet. Body composition was measured by bioelectrical impedance spectroscopy in patients without implants (n = 45). Regardless of treatment, fat-free mass increased and fat mass percentage decreased during weight stability, but no differences between intervention and control in the whole group (n = 42, all p > 0.20) were found. Interaction analysis revealed that participants who were non-employed (n = 15) significantly decreased in fat mass (-1.767 kg; 95% CI: -3.060, -0.475, p = 0.012) and fat mass percentage (-1.805%; 95% CI: -3.024, -0.586, p = 0.008) from the intervention compared to the control period. A Mediterranean-style diet improved body composition in non-employed participants (n = 15). The group as a whole improved regardless of dietary allocation, indicating a potential to treat rheumatoid cachexia by dietary manipulation.
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| 8. |
- Hulander, Erik, et al.
(författare)
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Proposed Anti-Inflammatory Diet Reduces Inflammation in Compliant, Weight-Stable Patients with Rheumatoid Arthritis in a Randomized Controlled Crossover Trial
- 2021
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166. ; 151:12, s. 3856-3864
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unclear to what extent adjuvant dietary intervention can influence inflammation in rheumatoid arthritis (RA). Objectives: The objective was to assess the effects of dietary manipulation on inflammation in patients with RA. Methods: In a crossover design, participants [n = 50, 78% females, median BMI (in kg/m2) 27, median age 63 y] were randomly assigned to begin with either a 10-wk portfolio diet of proposed anti-inflammatory foods (i.e., a high intake of fatty fish, whole grains, fruits, nuts, and berries) or a control diet resembling a Western diet with a 4-mo washout in between. This report evaluates the secondary outcome markers of inflammation among participants with stable medication. Analyses were performed using a linear mixed ANCOVA model. Results: There were no significant effects on CRP or ESR in the group as a whole. In those with high compliance (n = 29), changes in ESR within the intervention diet period differed significantly compared with changes within the control diet period (mean: -5.490; 95% CI: -10.310, -0.669; P = 0.027). During the intervention diet period, there were lowered serum concentrations of C-X-C motif ligand 1 (CXCL1) (mean: -0.268; 95% CI: -0.452, -0.084;P = 0.006), CXCL5 (mean: -0.278; 95% CI: -0.530, -0.026 P = 0.031), CXCL6 (mean: -0.251; 95% CI: -0.433, -0.069; P = 0.009), and tumor necrosis factor ligand superfamily member 14 (TNFSF14) (mean: -0.139; 95% CI: -0.275, -0.002; P = 0.047) compared with changes within the control diet period. Conclusion: A proposed anti-inflammatory diet likely reduced systemic inflammation, as indicated by a decreased ESR in those who completed the study with high compliance (n = 29). These findings warrant further studies to validate our results, and to evaluate the clinical relevance of changes in CXCL1, CXCL5, CXCL6, and TNFSF14 in patients with RA. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.
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| 9. |
- Levin, Malin, 1973, et al.
(författare)
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Evaluation of macrophage-specific promoters using lentiviral delivery in mice.
- 2012
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Ingår i: Gene therapy. - : Springer Science and Business Media LLC. - 1476-5462 .- 0969-7128. ; 19:11, s. 1041-7
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Tidskriftsartikel (refereegranskat)abstract
- In gene therapy, tissue-specific promoters are useful tools to direct transgene expression and improve efficiency and safety. Macrophage-specific promoters (MSPs) have previously been published using different delivery systems. In this study, we evaluated five different MSPs fused with green fluorescent protein (GFP) to delineate the one with highest specificity using lentiviral delivery. We compared three variants of the CD68 promoter (full length, the 343-bp proximal part and the 150-bp proximal part) and two variants (in forward and reverse orientation) of a previously characterized synthetic promoter derived from elements of transcription factor genes. We transduced a number of cell lines and primary cells in vitro. In addition, hematopoietic stem cells were transduced with MSPs and transferred into lethally irradiated recipient mice. Fluorescence activated cell sorting analysis was performed to determine the GFP expression in different cell populations both in vitro and in vivo. We showed that MSPs can efficiently be used for lentiviral gene delivery and that the 150-bp proximal part of the CD68 promoter provides primarily macrophage-specific expression of GFP. We propose that this is the best currently available MSP to use for directing transgene expression to macrophage populations in vivo using lentiviral vectors.
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| 10. |
- Lindqvist, Helen, 1977, et al.
(författare)
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A Randomized Controlled Dietary Intervention Improved the Serum Lipid Signature towards a Less Atherogenic Profile in Patients with Rheumatoid Arthritis
- 2021
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Diet is a major modifiable risk factor for cardiovascular disease (CVD). One explanation for this is its effect on specific lipids. However, knowledge on how the lipidome is affected is limited. We aimed to investigate if diet can change the new ceramide- and phospholipid-based CVD risk score CERT2 and the serum lipidome towards a more favorable CVD signature. In a crossover trial (ADIRA), 50 patients with rheumatoid arthritis (RA) had 10 weeks of a Mediterranean-style diet intervention or a Western-style control diet and then switched diets after a 4-month wash-out-period. Five hundred and thirty-eight individual lipids were measured in serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lipid risk scores were analyzed by Wilcoxon signed-rank test or mixed model and lipidomic data with multivariate statistical methods. In the main analysis, including the 46 participants completing >= 1 diet period, there was no significant difference in CERT2 after the intervention compared with the control, although several CERT2 components were changed within periods. In addition, triacylglycerols, cholesteryl esters, phosphatidylcholines, alkylphosphatidylcholines and alkenylphosphatidylcholines had a healthier composition after the intervention compared to after the control diet. This trial indicates that certain dietary changes can improve the serum lipid signature towards a less atherogenic profile in patients with RA.
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