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Lipids in Health and Disease Aug 2023The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA).
METHODS
The literature and relevant reviews were searched for published clinical studies on the relationship between JIA and blood lipid levels. The Newcastle-Ottawa scale (NOS) was applied to evaluate the risk and methodological value of the included case‒control and cohort studies. Standardized mean differences (SMDs) and 95% confidence intervals were derived for all variables with adequate unprocessed data. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.
RESULTS
In total, 16 studies were incorporated through screening. The analysis findings revealed that the levels of very low-density lipoprotein cholesterol [SMD=-0.411, 95% CI (-0.774~-0.048), P = 0.026], high-density lipoprotein cholesterol [SMD=-0.528, 95% CI (-0.976~-0.079), P = 0.021], and apolipoprotein A1 [SMD=-1.050, 95% CI (-1.452~-0.647), P = 0.000] in JIA patients were statistically lower than those observed in healthy controls. The level of low-density lipoprotein cholesterol [SMD = 0.202, 95% CI (0.003 ~ 0.400), P = 0.046] was significantly higher in JIA patients than in healthy controls. In JIA patients, body mass index [SMD=-0.189, 95% CI (-0.690 ~ 0.311), P = 0.459], high-density lipoprotein [SMD =-1.235, 95% CI (-2.845 ~ 0.374), P = 0.133), low-density lipoprotein [SMD = 0.616, 95% CI (-0.813 ~ 2.046), P = 0.398), triglycerides (SMD = 0.278, 95% CI (-0.182 ~ 0.738), P = 0.236], total cholesterol [SMD=-0.073, 95% CI (-0.438 ~ 0.293), P = 0.696] and apolipoprotein B levels [SMD = 0.226, 95% CI (-0.133 ~ 0.585), P = 0.217] were not significantly different from those in healthy controls.
CONCLUSIONS
The outcomes of this meta-analysis suggest that dyslipidemia is common in JIA patients compared to healthy controls. Patients with JIA have a significantly increased risk of atherosclerosis and cardiovascular disease later in life.
Topics: Humans; Arthritis, Juvenile; Apolipoproteins B; Cholesterol, HDL; Cholesterol, LDL; Lipoproteins, HDL
PubMed: 37626321
DOI: 10.1186/s12944-023-01885-1 -
RMD Open Aug 2023The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood...
Children with extended oligoarticular and polyarticular juvenile idiopathic arthritis have alterations in B and T follicular cell subsets in peripheral blood and a cytokine profile sustaining B cell activation.
OBJECTIVES
The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood and the cytokine environment present in circulation in children with extended oligoarticular juvenile idiopathic arthritis (extended oligo JIA) and polyarticular JIA (poly JIA) when compared with healthy controls, children with persistent oligoarticular JIA (persistent oligo JIA) and adult JIA patients.
METHODS
Blood samples were collected from 105 JIA patients (children and adults) and 50 age-matched healthy individuals. The frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/or ELISA in all groups included.
RESULTS
The frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with extended oligo JIA and poly JIA, but not persistent oligo JIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared with controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in paediatric extended oligo JIA and poly JIA patients when compared with controls. These immunological alterations were not found in adult JIA patients in comparison to controls.
CONCLUSIONS
Our results suggest a potential role and/or activation profile of B and Th17-like Tfh cells in the pathogenesis of extended oligo JIA and poly JIA, but not persistent oligo JIA.
Topics: Humans; Child; Interleukin-17; Arthritis, Juvenile; Interleukin-6; T-Lymphocyte Subsets; Cytokines
PubMed: 37652558
DOI: 10.1136/rmdopen-2022-002901 -
Mediterranean Journal of Rheumatology Mar 2024We have summarised the existing evidence supporting the concept that systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are part of the... (Review)
Review
AIM
We have summarised the existing evidence supporting the concept that systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are part of the same Still's disease spectrum.
METHODS
A PubMed/Embase database search was conducted using specific search strings and free text words to screen for relevant articles. The search was limited to studies in humans, published up to June 2023, in English-language.
SUMMARY
sJIA and AOSD are rare autoinflammatory disorders that have similar pathophysiological and clinical features. The clinical presentations of sJIA and AOSD are highly variable, with differential diagnoses that include a broad range of malignancies, infectious diseases, and autoimmune disorders, which contribute to delays in diagnosis. Several sets of classification exist to help diagnose patients in clinical practice; the International League of Associations for Rheumatology criteria for sJIA and the Yamaguchi and Fautrel criteria for AOSD are the most-used criteria. The therapeutic strategy for Still's disease aims to relieve signs and symptoms, prevent irreversible joint damage and potentially life-threatening complications, and avoid deleterious side effects of treatment. Recently, targeted therapies such as interleukin (IL)-1 and IL-6 inhibitors have become available for the treatment of sJIA and AOSD. While these biologics were originally largely reserved for patients in whom non-steroidal anti-inflammatory drugs, corticosteroids and conventional synthetic disease-modifying anti-rheumatic drugs had failed, they are increasingly used earlier in the treatment paradigm. Among IL-1 inhibitors, canakinumab is the only biologic approved in the US for the treatment of both sJIA and AOSD.
PubMed: 38756937
DOI: 10.31138/mjr.290323.dat -
Arthritis Research & Therapy Oct 2023Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. Some patients remain in an active state even though they were administrated with a combination of...
OBJECTIVES
Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. Some patients remain in an active state even though they were administrated with a combination of corticosteroid and methotrexate. Existing research has suggested that interferon and Janus kinase played an important role in pathogenesis. Existing research has suggested the efficacy of JAK inhibitors (JAKi). Our retrospective study aimed to investigate the efficacy of tofacitinib in refractory JDM patients.
METHODS
A total of eighty-eight patients in China who had been diagnosed with JDM and subjected to tofacitinib therapy for over 3 months were retrospectively analyzed. Skin and muscle manifestations were assessed using the Cutaneous Assessment Tool-binary method (CAT-BM), Childhood Myositis Assessment Scale (CMAS), and kinase. Pulmonary function was assessed using a high-resolution CT (computerized tomography) scan and pulmonary symptoms. All patients were subjected to regular follow-up, and core measures were assessed every 3 months after initiation. Furthermore, the data were analyzed using the Wilcoxon single test, Mann-Whitney U test, and chi-square test.
RESULTS
Compared with the baseline data, skin and muscle manifestations were found significantly improved during the respective follow-up visit. At the most recent follow-up, nearly 50% of patients achieved a clinical complete response and six patients received tofacitinib monotherapy. Sixty percent of patients suffering from interstitial lung disease well recovered on high-resolution CT. Seventy-five percent of patients showed a reduction in the size or number of calcinosis, and 25% of patients showed completely resolved calcinosis.
CONCLUSION
In this study, the result suggested that tofacitinib therapy exerted a certain effect on skin manifestations, muscle manifestations, interstitial lung disease (ILD), calcinosis, as well as downgrade of medication. In-depth research should be conducted to focus on the correlation between the pathogenesis of JDM and JAKi.
Topics: Humans; Child; Dermatomyositis; Retrospective Studies; Janus Kinase Inhibitors; Lung Diseases, Interstitial; Calcinosis
PubMed: 37853451
DOI: 10.1186/s13075-023-03170-z -
Zeitschrift Fur Rheumatologie Feb 2024This study aimed to update the prevalence estimates of inflammatory rheumatic diseases (IRD) in Germany.
OBJECTIVE
This study aimed to update the prevalence estimates of inflammatory rheumatic diseases (IRD) in Germany.
METHODS
A systematic literature search in PubMed and Web of Science (last search 08 November 2022) identified original articles (regional and nationwide surveys and claims data analyses for arthritides, connective tissue diseases, and vasculitides) on prevalences for the period 2014-2022. Data sources, collection period, case definition, and risk of bias are reported. Prevalences were estimated from available national data, with consideration of international data.
RESULTS
Screening by two authors yielded 263 hits, of which 18 claims data analyses and 2 surveys met the inclusion criteria. Prevalences ranged from 0.42 to 1.85% (rheumatoid arthritis), 0.32-0.5% (ankylosing spondylitis), 0.11-0.32% (psoriatic arthritis), 0.037-0.14% (systemic lupus erythematosus), 0.07-0.77% (Sjögren's disease/sicca syndrome), 0.14-0.15% (polymyalgia rheumatica, ≥ 40 years), 0.04-0.05% (giant cell arteritis, ≥ 50 years), and 0.015-0.026% (ANCA-associated vasculitis). The risk of bias was moderate in 13 and high in 7 studies. Based on the results, we estimate the prevalence of IRD in Germany to be 2.2-3.0%, which corresponds to approximately 1.5-2.1 million affected individuals. The prevalence of juvenile idiopathic arthritis was reported to be around 0.10% (0.07-0.10%) of 0-18-year-olds, corresponding to about 14,000 children and adolescents in Germany.
CONCLUSION
This systematic review shows an increase in the prevalence of IRD in Germany, which is almost exclusively based on claims data analyses. In the absence of multistage population studies, the available data are, overall, uncertain sources for prevalence estimates, with a moderate to high risk of bias.
Topics: Child; Adolescent; Humans; Prevalence; Arthritis, Rheumatoid; Spondylitis, Ankylosing; Polymyalgia Rheumatica; Sjogren's Syndrome; Lupus Erythematosus, Systemic; Rheumatic Fever; Giant Cell Arteritis; Rheumatic Diseases
PubMed: 36749363
DOI: 10.1007/s00393-022-01302-5 -
Frontiers in Immunology 2023Among immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies, particularly in Juvenile Idiopathic Arthritis...
INTRODUCTION
Among immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies, particularly in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. The uncontrolled activation of monocytes and excessive production of inflammatory factors contribute to the damage of bone-cartilage joints. Despite the moderate beneficial effect of current therapies and clinical trials, there is still a need for alternative strategies targeting monocytes to treat RA.
METHODS
To explore such an alternative strategy, we investigated the effects of targeting the CXCR4 receptor using the histamine analog clobenpropit (CB). Monocytes were isolated from the blood and synovial fluids of JIA patients to assess CB's impact on their production of key inflammatory cytokines. Additionally, we administered daily intraperitoneal CB treatment to arthritic mice to evaluate its effects on circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, as indicators of disease progression.
RESULTS
Our findings demonstrated that CXCR4 targeting with CB significantly inhibited the spontaneous and induced-production of key inflammatory cytokines by monocytes isolated from JIA patients. Furthermore, CB treatment in a mouse model of collagen-induce arthritis resulted in a significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, leading to a reduction in disease progression.
DISCUSSION
In conclusion, targeting CXCR4 with the small amino compound CB shows promise as a therapeutic option for chronic and viral-induced inflammatory diseases, including RA. CB effectively regulated inflammatory cytokine production of monocytes, presenting a potential targeted approach with potential advantages over current therapies. These results warrant further research and clinical trials to explore the full therapeutic potential of targeting CXCR4 with CB-like molecules in the management of various inflammatory diseases.
Topics: Animals; Humans; Mice; Arthritis, Juvenile; Arthritis, Rheumatoid; Bone Resorption; Cytokines; Disease Progression; Histamine; Inflammation; Receptors, CXCR4
PubMed: 37822935
DOI: 10.3389/fimmu.2023.1178172 -
International Journal of Molecular... Aug 2023The impact of JAK/STAT inhibitors, which are used in various inflammatory diseases, on cardiovascular risk is controversial and has recently raised safety concerns. Our...
The impact of JAK/STAT inhibitors, which are used in various inflammatory diseases, on cardiovascular risk is controversial and has recently raised safety concerns. Our study investigates the direct effects of tofacitinib on macrophage cholesterol metabolism, which is crucial for atherosclerosis plaque development and stability. Cultured human macrophages THP-1 were used to assess the impact of tofacitinib on cell cholesterol efflux and synthesis via radioisotopic methods, and on cholesterol uptake by measuring the cell cholesterol content with a fluorometric assay. The cholesterol acceptors and donors were either standard lipoproteins or sera from patients with juvenile idiopathic arthritis (JIA) and from control subjects. Tofacitinib significantly increased the macrophage cholesterol efflux to all acceptors; it reduced cholesterol uptake from both the normal and hypercholesterolemic sera; and it reduced cholesterol synthesis. The treatment of macrophages with tofacitinib was able to increase the cholesterol efflux and decrease cholesterol uptake when using sera from untreated JIA patients with active disease as cholesterol acceptors and donors, respectively. In conclusion, our in vitro data support the concept that tofacitinib has a favorable impact on macrophage cholesterol metabolism, even in the presence of sera from rheumatologic patients, and suggest that other mechanisms may be responsible for the cardiovascular risk associated with tofacitinib use in selected patient populations.
Topics: Humans; Lipid Metabolism; Piperidines; Arthritis, Juvenile; Janus Kinase Inhibitors; Macrophages
PubMed: 37628747
DOI: 10.3390/ijms241612571 -
Pediatric Rheumatology Online Journal Sep 2023In juvenile idiopathic arthritis (JIA) clinical remission is unattainable in some patients despite modern biologic disease-modifying antirheumatic drugs (bDMARD) therapy... (Observational Study)
Observational Study
BACKGROUND
In juvenile idiopathic arthritis (JIA) clinical remission is unattainable in some patients despite modern biologic disease-modifying antirheumatic drugs (bDMARD) therapy and switching bDMARD is required. The best choice of second-line bDMARD remains unclear. This retrospective observational study aims to describe the pattern, timing, frequency, and reasons for bDMARD switching among children diagnosed with non-systemic JIA.
METHODS
Patients were identified by combining unique personal identification numbers, the International Code of Diagnosis (ICD10) for JIA and biologic therapy. Clinical characteristics were collected retrospectively from the electronic medical records. Included were 200 children diagnosed with non-systemic JIA initiating their first biologic drug between January 1st, 2012, and March 1st, 2021. We compared characteristics of non-switchers vs switchers and early switchers (≤ 6 months) vs late switchers (> 6 months).
RESULTS
The median age at diagnosis was 7.7 years. We found that 37% switched to a different bDMARD after a median age of 6.3 years after diagnosis. In total, and 17.5% of patients switched at least twice, while 6% switched three or more times. The most common reason for switching was inefficacy (57%) followed by injection/infusion reactions (15%) and uveitis (13%). 77% were late switchers, and switched primarily due to inefficacy. All patients started a tumor necrosis factor inhibitor (TNFi) as initial bDMARD (Etanercept (ETN): 49.5%, other TNFis: 50.5%). The patients who started ETN as first-line bDMARD were more likely to be switchers compared to those who started another TNFi.
CONCLUSION
During a median 6.3-year follow-up biologic switching was observed in more than one third, primarily due to inefficacy.
Topics: Humans; Child; Arthritis, Juvenile; Retrospective Studies; Antirheumatic Agents; Etanercept; Tumor Necrosis Factor Inhibitors; Biological Products
PubMed: 37742033
DOI: 10.1186/s12969-023-00897-6 -
RMD Open Dec 2023This study investigates the diagnostic role of synovial tissue analysis in children presenting with arthritis and assesses its prognostic significance to predict...
OBJECTIVES
This study investigates the diagnostic role of synovial tissue analysis in children presenting with arthritis and assesses its prognostic significance to predict clinical outcome in juvenile idiopathic arthritis (JIA).
METHODS
Synovial samples of paediatric patients undergoing synovial biopsy between 1995 and 2020 were analysed histologically and immunohistochemically. Relationships between histological/immunohistochemical parameters and clinical variables were assessed.
RESULTS
Synovial biopsy was performed for diagnosis in 65 cases allowing to correctly classify 79% of patients.At histological analysis on 42 JIA samples, any difference in the number of synovial lining layers, subsynovial elementary lesions, fibrin deposit, Krenn Synovitis Score, inflammatory infiltrate score and pattern emerged between JIA subsets or on treatment exposure. Synovial tissue analysis predicted outcome: higher number of synovial layers predicted worse disease course (>4 flares during follow-up; 4.5 vs 3.0, p=0.035), even after adjusting for age at diagnosis and observation time (OR 2.2, p=0.007); subjects who had switched>2 biological disease-modifying antirheumatic drugs had higher prevalence of subsynovial elementary lesions (55.6% vs 10.3%, p=0.005) and fibrin deposits in synovial lining (60.0% vs 22.6%, p=0.049), even after adjustment for observation time and age at diagnosis (OR 8.1, p=0.047). At immunohistochemistry on 31 JIA samples, higher CD3 expression was described in polyarticular compared with oligoarticular subset (p=0.040). Patients with severe disease course had higher CD20+ rate (OR 7, p=0.023), regardless of JIA subset and treatment exposure.
CONCLUSIONS
Synovial tissue analysis might support the clinicians in the diagnostic approach of paediatric patients presenting with arthritis and guide the clinical management in JIA.
Topics: Humans; Child; Arthritis, Juvenile; Prognosis; Synovial Membrane; Synovitis; Disease Progression; Fibrin
PubMed: 38097272
DOI: 10.1136/rmdopen-2023-003296 -
Arthritis Research & Therapy Feb 2024Juvenile idiopathic arthritis (JIA) is one of the most prevalent rheumatic disorders in children and is classified as an autoimmune disease (AID). While a robust genetic...
BACKGROUND
Juvenile idiopathic arthritis (JIA) is one of the most prevalent rheumatic disorders in children and is classified as an autoimmune disease (AID). While a robust genetic contribution to JIA etiology has been established, the exact pathogenesis remains unclear.
METHODS
To prioritize biologically interpretable susceptibility genes and proteins for JIA, we conducted transcriptome-wide and proteome-wide association studies (TWAS/PWAS). Then, to understand the genetic architecture of JIA, we systematically analyzed single-nucleotide polymorphism (SNP)-based heritability, a signature of natural selection, and polygenicity. Next, we conducted HLA typing using multi-ethnicity RNA sequencing data. Additionally, we examined the T cell receptor (TCR) repertoire at a single-cell level to explore the potential links between immunity and JIA risk.
RESULTS
We have identified 19 TWAS genes and two PWAS proteins associated with JIA risks. Furthermore, we observe that the heritability and cell type enrichment analysis of JIA are enriched in T lymphocytes and HLA regions and that JIA shows higher polygenicity compared to other AIDs. In multi-ancestry HLA typing, B*45:01 is more prevalent in African JIA patients than in European JIA patients, whereas DQA1*01:01, DQA1*03:01, and DRB1*04:01 exhibit a higher frequency in European JIA patients. Using single-cell immune repertoire analysis, we identify clonally expanded T cell subpopulations in JIA patients, including CXCL13BHLHE40 T cells which are significantly associated with JIA risks.
CONCLUSION
Our findings shed new light on the pathogenesis of JIA and provide a strong foundation for future mechanistic studies aimed at uncovering the molecular drivers of JIA.
Topics: Child; Humans; Arthritis, Juvenile; Genetic Predisposition to Disease; Proteins; Alleles
PubMed: 38336809
DOI: 10.1186/s13075-024-03280-2