| 1. |
- 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, s. 1233-1242
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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 24weeks 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 24weeks, 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Lindqvist, Helen, 1977, et al.
(författare)
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Exploring the differences in serum metabolite profiles after intake of red meat in women with rheumatoid arthritis and a matched control group
- 2024
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Ingår i: European Journal of Nutrition. - 1436-6207. ; 63:1, s. 221-230
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Tidskriftsartikel (refereegranskat)abstract
- PurposeStudies have suggested that women with RA tend to avoid red meat more often than women without RA, based on their perception that it exacerbates their symptoms. Therefore, the aim of this study is to investigate and compare the postprandial metabolic response following the consumption of a red meat meal in patients with RA and a matched control group.MethodsParticipants were challenged with a meal with red meat and blood samples were collected before and at 0.5, 1, 2, 3 and 5 h after the meal. Serum metabolites were quantified by Nuclear Magnetic Resonance (NMR) analysis. Orthogonal Projections to Latent Structures with Discriminant Analysis (OPLS-DA) was used to evaluate separation by metabolites due to diagnosis of RA or not and to identify changes in metabolites related to RA. Incremental area under the curve was calculated for univariate comparisons for 23 metabolites.ResultsThe matched groups, including 22 women with RA and 22 women without RA, did not differ significantly in age, body mass index, diet quality or reported physical activity. OPLS-DA models had a limited quality indicating that there were no differences in metabolite patterns between the groups. However, phenylalanine was significantly higher in concentration in women with RA compared to controls in both fasting and postprandial samples.ConclusionTo conclude, this well-controlled postprandial intervention study found a significantly higher concentration of phenylalanine in both fasting and postprandial samples of women with RA compared to matched women without RA. These findings warrant further investigation in larger studies.
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| 8. |
- Lindqvist, Helen, 1977, et al.
(författare)
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Influence of Dietary n-3 Long Chain Polyunsaturated Fatty Acid Intake on Oxylipins in Erythrocytes of Women with Rheumatoid Arthritis
- 2023
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Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 28:2
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Tidskriftsartikel (refereegranskat)abstract
- Oxylipins derived from n-3 fatty acids are suggested as the link between these fatty acids and reduced inflammation. The aim of the present study was to explore the effect of a randomized controlled cross-over intervention on oxylipin patterns in erythrocytes. Twenty-three women with rheumatoid arthritis completed 2 x 11-weeks exchanging one cooked meal per day, 5 days a week, for a meal including 75 g blue mussels (source for n-3 fatty acids) or 75 g meat. Erythrocyte oxylipins were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were analyzed with multivariate data analysis. Orthogonal projections to latent structures (OPLS) with effect projections and with discriminant analysis were performed to compare the two diets' effects on oxylipins. Wilcoxon signed rank test was used to test pre and post values for each dietary period as well as post blue-mussel vs. post meat. The blue-mussel diet led to significant changes in a few oxylipins from the precursor fatty acids arachidonic acid and dihomo-gamma-linolenic acid. Despite significant changes in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and free EPA in erythrocytes in the mussel group, no concurrent changes in their oxylipins were seen. Further research is needed to study the link between n-3 fatty-acid intake, blood oxylipins, and inflammation.
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| 9. |
- Turesson Wadell, Anna, et al.
(författare)
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Dietary biomarkers and food records indicate compliance to study diets in the ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) trial
- 2023
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Ingår i: FRONTIERS IN NUTRITION. - 2296-861X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported intake of trial foods from telephone interviews. The aim of this study was to evaluate compliance using objective dietary biomarkers for whole grain, fruit and vegetables, margarine and oil, seafood and overall fat quality, as well as reported intake from food records of key components of the study diets. Methods: Fifty patients with rheumatoid arthritis were randomized to begin with the intervention diet (rich in whole grain, fruit and vegetables, margarine/oil and seafood) or the control diet (rich in meat and high-fat dairy) for 10 weeks, followed by a similar to 4 months wash-out period, and then switched diet. Compliance was evaluated using plasma alkylresorcinols (AR) as biomarkers for intake of whole grain wheat and rye, serum carotenoids for fruit and vegetables, plasma linoleic acid (LA, 18:2 n-6) and -alpha-linolenic acid (18:3, n-3) for margarine and cooking oil, plasma eicosapentaenoic acid (EPA, 20:5 n-3), -docosahexaenoic acid (DHA 22:6, n-3) and -docosapentaenoic acid (22:5 n-3) for seafood, and plasma fatty acid pattern for the overall dietary fat quality. Reported intake of whole grain, fruit, berries and vegetables, seafood, red meat, and fat quality was extracted from 3-d food records. Results: Plasma AR C21:0 and C23:0, LA, EPA, and DHA were higher while total serum carotenoids were lower after the intervention diet period compared to the control diet period (AR and carotenoids: p = <0.05, fatty acids: p = <0.001). Reported intake of whole grain, fruit, berries and vegetables, and seafood was higher and reported intake of red meat was lower during the intervention diet period compared to the control diet period (p = <0.001). Plasma- and reported fatty acid pattern differed as intended between the diet periods. Conclusion: This study indicates that the participants in the ADIRA trial were compliant to the study diets regarding intake of whole grain, cooking fat, seafood, and red meat, and the intended overall dietary fat quality. Compliance to instructions on fruit- and vegetable intake remains uncertain.
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| 10. |
- Turesson Wadell, Anna, et al.
(författare)
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Effects on health-related quality of life in the randomized, controlled crossover trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis).
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Rheumatoid Arthritis (RA) often report impaired health-related quality of life (HrQoL) such as difficulties in daily life, pain, fatigue and an affected social life. Even when lowering disease activity, pharmacological treatment does not always resolve these factors. The aim of the study was to investigate if a proposed anti-inflammatory diet improves HrQoL in patients with RA. In this controlled crossover trial, 50 patients were randomized to start with either an intervention diet (anti-inflammatory) or a control diet (usual Swedish intake) for ten weeks followed by a wash out period before switching to the other diet. Participants received food equivalent to ~1100 kcal/day, five days/week, and instructions to consume similarly for the remaining meals. HrQoL was evaluated using Health Assessment Questionnaire (HAQ), 36-item Short Form Survey (SF-36), Visual Analogue Scales (VAS) for pain, fatigue and morning stiffness, and a time scale for morning stiffness. Forty-seven participants completed ≥1 diet period and were included in the main analyses. No significant difference between intervention and control diet at end of diet periods was observed for any outcome. However, significant improvements were obtained for SF-36 Physical Functioning (mean: 5.79, SE: 2.12, 95% CI: 1.58, 10.01) during the intervention diet period. When excluding participants with anti-rheumatic medication changes, the differences between diet periods increased for most outcomes, favoring the intervention diet period, and the difference for SF-36 Physical Functioning became significant (n = 25, mean: 7.90, 95% CI: 0.56, 15.24, p = 0.036). In main analyses, the proposed anti-inflammatory diet did not significantly improve HrQoL for patients with RA compared to control diet. In sub-analyses, significant improvements in physical functioning were detected. Larger studies with consistent medication use and in populations more affected by the disease may be needed to obtain conclusive evidence.
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