| 1. |
- Kahn, Robin, et al.
(författare)
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Capillary leak syndrome was associated with more severe multisystem inflammatory syndrome in children during the COVID-19 pandemic
- 2024
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - 0803-5253.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity. Methods: All eligible individuals aged 0–18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied. They were all included in the Pediatric Rheumatology Quality Register and clinical and laboratory data were compared between patients with and without CLS. Results: We included 31 patients (61% male) with MIS-C in the study. The median age at diagnosis was 10.6 years (range 1.99–17.15) and 45% developed CLS. All six patients who required intensive care had CLS. Patients with CLS also had a higher incidence of reduced cardiac function, measured as low ejection fraction. The CLS group exhibited significantly higher C-reactive protein values (p < 0.001) and N-terminal pro-B-type natriuretic peptide levels (p < 0.001), as well as lower platelet counts (p = 0.03), during the first week of treatment. Individuals with CLS also received more intense immunosuppression. Conclusion: CLS was a common complication of MIS-C in our study and these patients had a more severe disease course that required more intensive treatment.
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| 2. |
- Arve-Butler, Sabine, et al.
(författare)
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Identification of novel autoantigens as potential biomarkers in juvenile idiopathic arthritis associated uveitis
- 2023
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 10, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many children with juvenile idiopathic arthritis (JIA) have autoantibodies, targeting nuclear components (anti-nuclear antibodies, ANA). ANA in JIA is associated with uveitis, an eye inflammation which may cause permanent vision impairment if not detected and treated. However, ANA-testing is neither specific nor sensitive enough to be a clinically reliable predictor of uveitis risk, and the precise autoantigens targeted by ANA in JIA are largely unknown. If identified, specific autoantibodies highly associated with uveitis could be used as biomarkers to facilitate identification of JIA patients at risk.METHODS: Antibodies from six ANA-positive, oligoarticular JIA patients, with and without uveitis, were explored by two large-scale methods: (1) screening against 42,100 peptides on an autoimmunity profiling planar array, and (2) immunoprecipitations from cell lysates with antigen identification by mass spectrometry. Three hundred thirty-five peptide antigens, selected from proteins identified in the large-scale methods and the scientific literature were investigated using a bead-based array in a cohort of 56 patients with oligoarticular- or RF-negative polyarticular JIA, eight of which were having current or previous uveitis.RESULTS: In the planar array, reactivity was detected against 332 peptide antigens. The immunoprecipitations identified reactivity towards 131 proteins. Only two proteins were identified by both methods. In the bead-based array of selected peptide antigens, patients with uveitis had a generally higher autoreactivity, seen as higher median fluorescence intensity (MFI) across all antigens, compared to patients without uveitis. Reactivity towards 17 specific antigens was significantly higher in patients with uveitis compared to patients without uveitis. Hierarchical clustering revealed that patients with uveitis clustered together.CONCLUSION: This study investigated autoantigens in JIA and uveitis, by combining two exploratory methods and confirmation in a targeted array. JIA patients with current or a history of uveitis had significantly higher reactivity towards 17 autoantigens and a generally higher autoreactivity compared to JIA patients without uveitis. Hierarchical clustering suggests that a combination of certain autoantibodies, rather than reactivity towards one specific antigen, is associated with uveitis. Our analysis of autoantibodies associated with uveitis in JIA could be a starting point for identification of prognostic biomarkers useful in JIA clinical care.
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| 3. |
- Schmidt, Tobias, et al.
(författare)
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Synovial monocytes contribute to chronic inflammation in childhood-onset arthritis via IL-6/STAT signalling and cell-cell interactions
- 2023
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Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Monocytes are key effector cells in inflammatory processes. We and others have previously shown that synovial monocytes in childhood-onset arthritis are activated. However, very little is known about how they contribute to disease and attain their pathological features. Therefore, we set out to investigate the functional alterations of synovial monocytes in childhood-onset arthritis, how they acquire this phenotype, and whether these mechanisms could be used to tailorize treatment.METHODS: The function of synovial monocytes was analysed by assays believed to reflect key pathological events, such as T-cell activation-, efferocytosis- and cytokine production assays using flow cytometry in untreated oligoarticular juvenile idiopathic arthritis (oJIA) patients (n=33). The effect of synovial fluid on healthy monocytes was investigated through mass spectrometry and functional assays. To characterize pathways induced by synovial fluid, we utilized broad-spectrum phosphorylation assays and flow cytometry, as well as inhibitors to block specific pathways. Additional effects on monocytes were studied through co-cultures with fibroblast-like synoviocytes or migration in transwell systems.RESULTS: Synovial monocytes display functional alterations with inflammatory and regulatory features, e.g., increased ability to induce T-cell activation, resistance to cytokine production following activation with LPS and increased efferocytosis. In vitro, synovial fluid from patients induced the regulatory features in healthy monocytes, such as resistance to cytokine production and increased efferocytosis. IL-6/JAK/STAT signalling was identified as the main pathway induced by synovial fluid, which also was responsible for a majority of the induced features. The magnitude of synovial IL-6 driven activation in monocytes was reflected in circulating cytokine levels, reflecting two groups of low vs. high local and systemic inflammation. Remaining features, such as an increased ability to induce T-cell activation and markers of antigen presentation, could be induced by cell-cell interactions, specifically via co-culture with fibroblast-like synoviocytes. CONCLUSIONS: Synovial monocytes in childhood-onset arthritis are functionally affected and contribute to chronic inflammation, e.g., via promoting adaptive immune responses. These data support a role of monocytes in the pathogenesis of oJIA and highlight a group of patients more likely to benefit from targeting the IL-6/JAK/STAT axis to restore synovial homeostasis.
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| 4. |
- Berthold, Elisabet, et al.
(författare)
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The risk of depression and anxiety is not increased in individuals with juvenile idiopathic arthritis - results from the south-Swedish juvenile idiopathic arthritis cohort
- 2022
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Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 20:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildren with chronic diseases are reported to have increased risk of psychiatric comorbidity. Few studies have investigated this risk in juvenile idiopathic arthritis (JIA), with conflicting results. We performed a population-based, longitudinal cohort study of the risk of depression and anxiety in south-Swedish patients with juvenile arthritis.MethodsThe south-Swedish JIA cohort (n = 640), a population-based cohort with validated JIA diagnosis 1980 – 2010 and comparators, a reference group of 3200 individuals free from JIA, matched for sex, year of birth and residential region, was used. Data on comorbid diagnosis with depression or anxiety were obtained from the Skåne Healthcare Register, containing all healthcare contacts in the region, from 1998 to 2019. We used Cox proportional models for the calculation of hazard ratios.ResultsDuring the study period, 1998 to 2019, 93 (14.5%) of the individuals in the JIA group were diagnosed with depression, and 111 (17.3%) with anxiety. Corresponding numbers among the references was 474 (14.8%) with depression and 557 (17.4%) with anxiety. Hazard ratio for depression was 1.1 (95% CI 0.9 – 1.5) in females and 0.8 (95% CI 0.5 – 1.4) in males, and for anxiety 1.2 (95% CI 0.9 – 1.5) in females and 0.6 (95% CI 0.4 – 1.1) in males. There were no statistically significant hazard ratios when analyzing subgroups of JIA patients with long disease duration or treatment with disease-modifying antirheumatic drugs.ConclusionsIndividuals with JIA do not have any statistically increased risk of being diagnosed with depression or anxiety compared to matched references.
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| 5. |
- Kahn, Robin, et al.
(författare)
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Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms
- 2022
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8 weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2 weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8 weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8 weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
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| 6. |
- Ödman, Anders, et al.
(författare)
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Stenar kan tala! : Vä kyrka i klarare belysning
- 2021
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Ingår i: Vä kyrka 900 år : 2021 - 2021. - 9789152709535 ; , s. 55-101
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- En byggnads och stilanalys visar koret sannolikt varit ett solitärt kapell byggt på 1000-talet. Genom dendrokronologiska dateringar har en sannolik datering till omkring 1120 också för det romanska måleriet framkommit. Två valvbärande kolonner visar sig vara av lokal Önnestadsyenit vilka har hämtats i blockterräng vid Djurröd och sannolikt polerats i Vä. Det sannolika polerverkat undersöktes på 1960-talet av arkeologer men först nu kan dess funktion sökas.
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| 7. |
- Schmidt, Tobias, et al.
(författare)
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Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment - a distinct inflammatory pattern for oligoarticular juvenile arthritis
- 2020
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA). Methods Paired synovial fluid, blood samples (n = 13), and synovial biopsies (n = 3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro. Monocyte/macrophage distribution, polarization, and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence, and in situ hybridization. Results Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNγ)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p < 0.001), CD86 (p < 0.001), and CD206 (p < 0.001), but not CD163, as compared to paired circulating monocytes. Additionally, polarization was extensively explored at the mRNA level and synovial fluid monocytes differentially expressed classical markers of M1(IFNγ)/M2(IL-4) polarization compared to circulating monocytes. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p < 0.01). Synovial fluid induced M2 markers (CD16 and CD206), but not M1 (CD40) or CD86 in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies. Conclusion Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies.
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| 8. |
- Berthold, Elisabet, et al.
(författare)
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Outcome in Juvenile Idiopathic arthritis : a population-based study from Sweden
- 2019
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: As the treatment arsenal for children with juvenile idiopathic arthritis (JIA) has expanded during the last decades, follow-up studies are needed on children diagnosed in the era of biological treatment to evaluate if this has improved the outcome. Our aim was to study the epidemiology and outcome of JIA in southern Sweden using a population-based cohort of children with a validated diagnosis of JIA collected over 9 years. Methods: Potential cases of JIA between 2002 and 2010 were collected after a database search, using the ICD codes M08-M09. The study area was Skåne, the southernmost county of Sweden (population 1.24 million; 17.6% aged < 16 years). The JIA diagnosis was validated and subcategorized through medical record review based on the criteria defined by the International League of Associations for Rheumatism (ILAR). Parameters on disease activity and pharmacologic treatment were recorded annually until the end of the study period (December 31, 2015). Results: In total, 251 cases of JIA were confirmed. The mean annual incidence rate for JIA was estimated to be 12.8/100,000 children < 16 years, with the highest age-specific annual incidence at the age of 2 years (36/100,000). Oligoarthritis was the largest subgroup (44.7%), and systemic JIA was the smallest subgroup (2.8%). Methotrexate was the most common disease-modifying anti-rheumatic drug prescribed (60.6%). Tumor necrosis factor alpha inhibitors were used as treatment for 23.9% of the children. Only 40.0% of the follow-up years, with a median follow-up time of 8 years, were free of arthritis or uveitis. Uveitis occurred in 10.8% of the children (8.0% chronic uveitis), and the need for joint corrective orthopedic surgery was 9.2%. Conclusions: The incidence of JIA in this well-defined, population-based cohort is slightly lower than in previously published studies from Scandinavia. The need for orthopedic surgery and the presence of uveitis are diminished compared to studies with patients diagnosed more than 20 years ago. Children with JIA however still experience disease activity more than 50% of the time. In conclusion, we still have long-term challenges in the care for children with JIA, in spite of state-of-the-art treatment.
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