Polyarticular Juvenile Idiopathic Arthritis Research Articles

A population pharmacokinetic model using allometric scaling for baricitinib in patients with juvenile idiopathic arthritis.

Baricitinib is approved for the treatment of rheumatoid arthritis (RA) in more than 70 countries, and juvenile idiopathic arthritis (JIA) in the European Union. Population pharmacokinetic (PK) models were developed in a phase 3 trial to characterize PK in pediatric patients with JIA and identify weight-based dosing regimens. The phase 3, randomized, double-blind, placebo-controlled withdrawal, efficacy and safety trial, JUVE-BASIS, enrolled patients (aged 2 to <18 years) with polyarticular course JIA. During a safety/PK period, baricitinib concentration data from age-based dose cohorts were compared to concentrations from adult patients receiving 4-mg QD. PK data were used to develop a population PK model with allometric scaling to determine a weight-based posology in pediatric patients with JIA that matched the adult 4-mg exposure. Baricitinib plasma concentrations from 217 pediatric patients were used to characterize PK. Based on the adult model, pediatric PK was best described using a 2-compartment model with allometric scaling on clearance and volume of distribution and renal function (estimated with glomerular filtration rate [GFR], a known covariate affecting PK of baricitinib) on clearance. The PK modeling suggested the optimal dosing regimen based on weight for pediatric patients as: 2-mg QD for patients 10 to <30 kg and 4-mg QD for patients ≥30 kg. The use of a population PK model of baricitinib treatment in adult patients with RA, with the addition of allometric scaling for weight on clearance and volume terms, was useful to predict exposures and identify weight-based dosing in pediatric patients with JIA.

Assessment of Bone Mineral Density in a cohort of Juvenile Idiopathic Arthritis patients

Introduction: Low bone mass is encountered in patients with Juvenile idiopathic arthritis (JIA) as a serious long-term complication of this pediatric condition and may be associated with fractures and its complications.&#x0D; The present study aimed to evaluate the frequency of low bone mineral density (BMD) and fragility fractures in patients with JIA in its polyarticular or oligo articular forms. Secondary, our aim was to identify factors associated with low bone mass.&#x0D; Patients and methods: This is a retrospective study conducted on 26 patients with JIA meeting the ILAR criteria for poly or oligoarticular form. Patients were divided into two groups according to their age : group1 including patients aged over 16 years-old and group 2 including patients aged under 16 years-old. Sociodemographic, clinical, biological and functional data were collected by consulting patient’s medical records. Bone mineral density was measured at three different sites: whole body, lumbar spine and hip using the dual-energy X-ray absorptiometry (DXA) equipment. Data were entered and analyzed using SPSS version 11.5 software.&#x0D; Results: Twenty-six JIA patients including 20 females (74.1%) and six males (22.2%) were enrolled with a mean disease duration of 20.23 years [2-54 years]. The mean age was 28.2 years [7-58 years]. The distribution of JIA subtypes among patients was as follows: 6 with oligo articular JIA and 20 with polyarticular JIA. Sixteen patients (59%) practiced regular physical activity. In our series, the frequency of low bone mineral density was 41% in children with JIA and 68 % in adults with JIA. Only two patients presented a fragility fracture in adulthood represented by a hip fracture following low-energy trauma and treated surgically in both cases. No patient received an anti-osteoporotic treatment. In-group 1, there was a significant correlation between low bone mass and weight (p=0.020), BMI (p=0.028), disease duration (p=0.045), positivity of AAN (p=0.050), disease activity (p=0.019), oral corticosteroid (p=0.034) and biologic treatment (p=0.043). In-group 2, a statistically significant correlation was found between low bone mass and age at the time of JIA diagnosis (p=0.041), weight (p=0.03), physical activity (p=0.05), disease duration (p=0.021), functional impact of the disease assessed by the HAQ score (p=0.018), oral corticosteroid therapy (p=0.014) and biological therapy (p=0.012).&#x0D; Conclusion: our study showed that a combination of factors contributed to compromise bone health in patients with JIA. Fragility fractures were rare and occurring mainly in adulthood. An adequate control of disease activity, proper management of treatment, adequate calcium and vitamin D intake, as well as regular physical activity, may contribute to preserve bone health in those patients.

Evaluation of medication withdrawal in patients with non-systemic juvenile idiopathic arthritis in Japan using a web-based survey.

Although treatments for juvenile idiopathic arthritis (JIA) have seen considerable advancements, there remains a lack of clear guidelines on withdrawing medications. This study aimed to investigate the current strategies for discontinuing non-systemic JIA treatment. A web-based questionnaire was distributed to members of the Pediatric Rheumatology Association of Japan. According to 126 responses, the most significant factors influencing JIA treatment tapering were the duration of clinically inactive disease, medication toxicity, and a history of arthritis flares. Respondents were often cautious about discontinuing medication if symptoms, e.g. 'morning stiffness' or 'intermittent joint pain', persisted. Among subtypes, oligoarticular JIA was more amenable to treatment tapering, whereas rheumatoid factor-positive polyarticular JIA proved less amenable. Most respondents started medication tapering after a continuous clinical inactive duration exceeding 12 months, and >50% of them required >6 months to achieve treatment discontinuation. Additionally, 40% of the respondents consistently underwent imaging before treatment tapering. The relative risks of treatment continuation and withdrawal should be considered, and decisions should be made accordingly. To obtain improved understanding of and more robust evidence for the optimal strategies for safely discontinuing JIA treatment, it is crucial to continue investigations including long-term outcomes.

Th17/1 and ex-Th17 cells are detected in patients with polyarticular juvenile arthritis and increase following treatment

BackgroundA better understanding of the pathogenesis of polyarticular juvenile idiopathic arthritis (polyJIA) is needed to aide in the development of data-driven approaches to guide selection between therapeutic options. One inflammatory pathway of interest is JAK-STAT signaling. STAT3 is a transcription factor critical to the differentiation of inflammatory T helper 17 cells (Th17s). Previous studies have demonstrated increased STAT3 activation in adult patients with rheumatoid arthritis, but less is known about STAT3 activation in polyJIA. We hypothesized that Th17 cells and STAT3 activation would be increased in treatment-naïve polyJIA patients compared to pediatric controls.MethodsBlood from 17 patients with polyJIA was collected at initial diagnosis and again if remission was achieved (post-treatment). Pediatric healthy controls were also collected. Peripheral blood mononuclear cells were isolated and CD4 + T cell subsets and STAT activation (phosphorylation) were evaluated using flow cytometry. Data were analyzed using Mann–Whitney U and Wilcoxon matched-pairs signed rank tests.ResultsTreatment-naïve polyJIA patients had increased Th17 cells (CD3 + CD4 + interleukin(IL)-17 +) compared to controls (0.15% v 0.44%, p < 0.05), but Tregs (CD3 + CD4 + CD25 + FOXP3 +) from patients did not differ from controls. Changes in STAT3 phosphorylation in CD4 + T cells following ex vivo stimulation were not significantly different in patients compared to controls. We identified dual IL-17 + and interferon (IFN)γ + expressing CD4 + T cells in patients, but not controls. Further, both Th17/1 s (CCR6 + CD161 + IFNγ + IL-17 +) and ex-Th17s (CCR6 + CD161 + IFNγ + IL-17neg) were increased in patients’ post-treatment (Th17/1: 0.3% v 0.07%, p < 0.05 and ex-Th17s: 2.3% v 1.4%, p < 0.05). The patients with the highest IL-17 expressing cells post-treatment remained therapy-bound.ConclusionsPatients with polyJIA have increased baseline Th17 cells, potentially reflecting higher tonic STAT3 activation in vivo. These quantifiable immune markers may identify patients that would benefit upfront from pathway-focused biologic therapies. Our data also suggest that inflammatory CD4 + T cell subsets not detected in controls but increased in post-treatment samples should be further evaluated as a tool to stratify patients in remission on medication. Future work will explore these proposed diagnostic and prognostic biomarkers.

Efficacy of accommodating variable-resistance training on muscle architecture, peak torque, and functional performance in patients with juvenile idiopathic arthritis: A randomized controlled trial

PurposeThis study sought to find out if a 6-week accommodating variable-resistance (AcVR) training might enhance muscle architecture, peak torque, and functional performance in patients with juvenile idiopathic arthritis (Juv-IA). MethodsFifty-eight patients with polyarticular Juv-IA (aged 12–18 years) were involved in a randomized controlled trial. They were allocated into two groups: the AcVR group (n = 29; underwent AcVR training, and the control group (n = 29; received the usual exercise regimen). Interventions were applied three times a week over six consecutive weeks. Measurements were done at baseline and after the intervention. The primary outcome measures were muscle architecture and peak torque, with functional capacity being the secondary measure. ResultsCompared to the control group, the AcVR group showed favorable pre-to-post changes in muscle architecture [fascicle length (P = 0.0007, η2p = .18), pennation angle (P = 0.0004, η2p = .20), and muscle thickness (P = 0.001, η2p = .17)]. Further, the AcVR group revealed a greater increase in peak concentric torque of knee extensors at angular speeds of 120°/sec [right side (P = 0.0032, η2p = .08); left side (P = 0.039, η2p = .07)] and 180°/sec [right side (P = 0.01, η2p = .11); left side (P = 0.014, η2p = .10)]. Furthermore, The AcVR group achieved more conducive changes in functional performance [6-min walk test (P = 0.003, η2p = .15), timed up and down stair test (P = 0.009, η2p = .12), and 4 × 10 m shuttle run test (P = 0.036, η2p = .08)]. ConclusionA 6-week AcVR training is potentially effective for improving muscle architectural qualities, enhancing peak muscle torque, and boosting functional performance in patients with Juv-IA without experiencing any detrimental side effects.

Application of the new PRINTO classification criteria for juvenile idiopathic arthritis in a sample of Portuguese patients.

The International League of Associations for Rheumatology (ILAR) classification system for juvenile idiopathic arthritis (JIA) does not depict homogenous subgroups of disease. As to unify our language with the adult rheumatic diseases, the Pediatric Rheumatology International Trials Organization (PRINTO) is attempting to revise these criteria. To reclassify a JIA sample according to the new provisional PRINTO subsets: systemic JIA (sJIA), RF-positive JIA (RF-JIA), early-onset ANA-positive JIA (eoANA-JIA), enthesitis/spondylitis-related JIA (ESR-JIA), "other JIA" and "unclassified JIA". Retrospective study including JIA patients followed in a Pediatric Rheumatology Unit at a university hospital. Medical records were reviewed, and patients were reclassified as per the provisional PRINTO criteria. Of a total of 104 patients, 41 (39.4%) were reclassified as "other JIA", 36 (34.6%) as eoANA-JIA, 15 (14.4%) as ESR-JIA, 8 (7.7%) as sJIA and 4 (3.8%) as RF-JIA. More than 90% of the oligoarticular JIA were reclassified into either eoANA-JIA or "other JIA". Only one negative RF polyarticular JIA converted to RF-JIA due to the presence of a positive anti-citrulinated peptide antibody (ACPA). The psoriatic arthritis (PsA) subgroup disappeared into eoANA-JIA (25%), ESR-JIA (25%) or "other JIA" (50%). There were significant differences in age of onset, but not on the gender ratio or uveitis presence. Antinuclear antibody was more frequent in females (p=0.035) and younger patients (p<0.001). The number of affected joints and PsA features elapsed in favour of laboratory RF, ACPA and ANA traits. PsA and oligoarticular JIA were abolished. The "other JIA" entity is heterogenous and prevalent, claiming reformulation.

Safety and efficacy of biologic immunosuppressive treatment in juvenile idiopathic arthritis associated with inborn errors of immunity.

This study aims to describe clinical features, therapeutic outcomes, and safety profiles in patients affected by juvenile idiopathic arthritis (JIA) and inborn errors of immunity (IEI) treated with biological Disease-modifying antirheumatic drugs (DMARDs). We enrolled three patients who were followed in the Pediatric Rheumatology Unit at Meyer Children's Hospital in Florence; these patients were affected by JIA, according to ILAR criteria, and IEI, according to the IUIS Phenotypical Classification for Human Inborn Errors of Immunity. Among them, two patients had 22q11.2 deletion syndrome (22q11.2DS) and one patient had X-linked agammaglobulinemia (XLA). Case 1: A 6-year and 2-month-old boy was affected by 22q11.2DS, associated with oligoarticular JIA, at the age of 2 years. He was treated with non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate, along with oral glucocorticoids but with no benefits. Treatment with etanercept allowed him to achieve remission after 10 months. Case 2: A 6-year and 2-month-old girl was affected by 22q11.2DS, associated with oligoarticular JIA, at the age of 3 years and 11 months. She was treated with NSAIDs, joint injections, and methotrexate but without clinical response. Treatment with Adalimumab allowed her to achieve remission after 6 months. Case 3: A 12-year and 2-month-old boy was affected by XLA, associated with polyarticular JIA, at the age of 9 years and 11 months. He was treated with NSAIDs, methotrexate, joint injections, and oral glucocorticoids with no benefits. He failed to respond to anti-TNF-alpha, tocilizumab, and abatacept. Currently, he is undergoing therapy with sirolimus plus abatacept, which allowed him to achieve remission after 4 months. Results suggest that the use of immunosuppressive biological therapies can control disease activity in these patients. No adverse drug-related reactions were observed during the follow-up.

Pediatric Rheumatological Diseases in a Tertiary Care Hospital of Central India: A Retrospective Clinico-Epidemiological Profile.

Introduction:Infectious diseases account for the major health problem in developing countries like India. Though non-infectious diseases like rheumatological disorders are not very common, the burden of these disorders as a group is high in society due to the huge population size. The rheumatological disorders have varied presentations which may mimic other infectious pathologies leading to a significant time lag in the diagnosis. There is inadequate data on the exact burden of these diseases. The spectrum of rheumatological disorders in developing countries is different as compared to the Western world.Hence this study was carried out with the aim of studying the clinical, epidemiological, and laboratory profile of rheumatological disorders in the pediatric age group in a tertiary care hospital. Methods:It was a retrospective study. Data of patients admitted with the diagnosis of rheumatological disorder in the age group of one month to 15 years during the period from June 2018 to December 2022 were reviewed. Results:A total of 35 patients were identified with 20 being female. The mean age of the patients was 8.42± 3.95 years. The most common disease was juvenile idiopathic arthritis (JIA)- 10(28.57%) with an equal proportion of polyarticular JIA and systemic-onset JIA, followed by systemic lupus erythematosus (SLE) nine (25.71%) and Kawasaki Disease (KD)- eight (22.85%). The commonest presenting complaint was fever followed by a rash, whereas the most common findings were pallor and rash. Anemia was present in 25 (71.42%). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in 20 (57.14%) and 22 (62.85%), respectively. Antinuclear antibodies (ANA) were positive in 10 (28.57%) and rheumatoid factor (RA) factor in only one (2.85%) case. Conclusions:The most common rheumatological disorder identified was JIA. Fever and rash were the common presenting complaints. Pallor was the commonest sign whereas anemia was the commonest hematological abnormality.

Increased neutrophil extracellular trap formation in oligoarticular, polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis: biomarkers for diagnosis and disease activity.

Neutrophil extracellular traps (NETs) are important factors in initiating and perpetuating inflammation. However, the role of NETs in different subtypes of juvenile idiopathic arthritis (JIA) has been rarely studied. Therefore, we aimed to explore the ability of JIA-derived neutrophils to release NETs and the effect of TNF-α (tumor necrosis factor-alpha) inhibitors on NET formation both in vitro and in vivo, and evaluate the associations of NET-derived products with clinical and immune-related parameters. The ability of neutrophils to release NETs and the effect of adalimumab on NET formation was assessed via in vitro stimulation and inhibition studies. Plasma NET-derived products were detected to assess the incidence of NET formation in vivo. Furthermore, flow cytometry and western blotting were used to detect NET-associated signaling components in neutrophils. Compared to those derived from HCs, neutrophils derived from patients with oligoarticular-JIA, polyarticular-JIA and enthesitis-related arthritis were more prone to generate NETs spontaneously and in response to TNF-α or PMA in vitro. Excessive NET formation existed in peripheral circulation of JIA patients, and elevated plasma levels of NET-derived products (cell-free DNA and MPO-DNA complexes) could accurately distinguish JIA patients from HCs and were positively correlated with disease activity. Multiple linear regression analysis showed that erythrocyte sedimentation rate and TNF-α levels were independent variables and were positively correlated with cell-free DNA concentration. Notably, TNF-α inhibitors could effectively prevent NET formation both in vitro and in vivo. Moreover, the phosphorylation levels of NET-associated kinases in JIA-derived neutrophils were markedly increased. Our data suggest that NETs might play pathogenic roles and may be involved in TNF-α-mediated inflammation in JIA. Circulating NET-derived products possess potential diagnostic and disease monitoring value. Furthermore, the preliminary results related to the molecular mechanisms of NET formation in JIA patients provide a theoretical basis for NET-targeted therapy.

Using a collaborative learning health system approach to improve disease activity outcomes in children with juvenile idiopathic arthritis in the Pediatric Rheumatology Care and Outcomes Improvement Network.

The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023. Twenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care. Five outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6. PR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality.

Differential type I and type III interferon expression profiles in rheumatoid and juvenile idiopathic arthritis.

The role of type I and type III interferons (IFNs) in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) is still poorly understood. The objective of this study was to examine the hypothesis that IFN expression profiles in the peripheral blood differ between subsets of arthritic subjects. Multiple type I and type III IFNs were examined in patients with RA and JIA, as well as among subtypes of JIA. Treatment-naïve RA and JIA patients were enrolled. Droplet digital PCR was used to measure the expression of type I, II, and III interferons in blood and synovial fluid leukocytes. Dendritic cell subsets were isolated from synovial fluid to examine IFN expression in each subset. Additionally, synovial mononuclear cells and JIA-derived fibroblast-like synoviocytes were stimulated with TNF, IFNγ, and poly(I:C) to examine inducible IFN expression. The predominant type I IFN gene expressed by blood leukocytes was IFNκ and was significantly lower in RA than JIA and controls. Oligoarticular and psoriatic JIA subgroups showed higher IFNκ expression compared to polyarticular JIA and RA. JIA synovial fluid leukocytes expressed abundant IFNγ and type III IFNs (IFNλ1, IFNλ3), with distinct dendritic cell subset contributions. JIA fibroblast-like synoviocytes produced IFNβ, IFNλ1, and IFNλ2 mRNA upon poly(I:C) stimulation. This study revealed differences in IFN expression patterns in RA and JIA, with notable differences between JIA subtypes. The expression levels of IFNκ, IFNγ, IFNλ1 and IFNλ3 in JIA suggest specific roles in disease pathology, influenced by disease subtype and joint microenvironment. This study contributes to understanding IFN-mediated mechanisms in arthritis, potentially guiding targeted therapeutic strategies.

Protocols in pediatric rheumatology (PROKIND): treat-to-target in polyarticular juvenile idiopathic arthritis

The aims of the PROKIND protocols are improvement and harmonization of the diagnostics, monitoring, treatment decision and prognosis. This article reports the results of a prospective treat-to-target observational study of patients with polyarticular juvenile idiopathic arthritis (JIA) during the first year of treatment. Disease activity was assessed with the 10-joint juvenile arthritis disease activity score (JADAS-10), functional limitation with the childhood health assessment questionnaire disability index (CHAQ-DI) and with information on overall well-being, on pain, on fatigue and on global estimation of disease activity. Overall, 129 patients with polyarticular JIA (rheumatoid factor, RF, positive (+) polyarthritis n = 22, RF negative (-) polyarthritis n = 133 from 23pediatric rheumatology institutions in Germany and Austria were recruited. Patients with initial treatment with methotrexate formed cohort1, patients with additional repeated intravenous corticosteroid pulse therapy formed cohort2 and patients with concomitant intra-articular corticosteroid administration in at least 5joints formed cohort3. The mean JADAS10 showed adecrease in disease activity from 16.4 ± 6.1 to 2.8 ± 3.6 and the decrease in the CHAQ-DI from 1.0 ± 0.8 to 0.3 ± 0.5 showed the improvement in functional capacity. Similarly, improvements in quality of life, pain and fatigue were demonstrable. A JADAS inactive disease was achieved by 18.1% at month3, 47.7% at month6 and66.7% at month12. In cohort 1 a JADAS remission was achieved by 72.4%, by 50% in cohort 2 and by 69.2% in cohort 3. An escalation to treatment with biologics was necessary in 38% of patients in cohort 1, 60% in cohort 2 and 46% in cohort 3. Using atreat-to-target approach a dramatic improvement in disease activity, functional capacity and quality of life in polyarticular JIA could be achieved. Even after 12months an inactive disease was achieved in the majority of cases.

Clinical and Demographic Profile of Patients with Juvenile Idiopathic Arthritis in a Tertiary Care Center in Mumbai, Western India

Abstract Background: Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic rheumatic disease affecting children younger than 16 years of age and lasting six weeks or longer. It causes both short-term and long-term disability. There are very few epidemiological studies from western India on JIA. The objectives of this study were to identify the clinical and demographic profile of JIA patients and compare to existing epidemiological data. Material and Methods: It was a retrospective observational study carried out at BJ Wadia Hospital for children in Mumbai, over a period of 30 months. The analysis of their clinical, demographic and treatment profile was done. Results: We had a total of 61 cases, 31 were male and 30 female. Maximum cases were of SoJIA and ERA (n=18 in each, 29.5%), followed by polyarticular JIA (n=16, 26.2%) and oligoarticular JIA (n=8, 13.1%). Knee (75.4%) was the commonest joint involved. Two patients had uveitis (one with chronic and other with acute anterior uveitis). The mean ESR was 72mm and CRP 45.87mg/dL. ANA was positive in 7 patients, whereas RF in 3 patients. There was a mean 6 months delay in their diagnosis, maximum being in polyarticular JIA with 11 months dealy. All patient were treated with NSAIDs (naproxen or indomathacin). cDmards were given for treatment - either methotrexate or sulfasalzine. Twelve were given biologicals DMARDs. Conclusion: SoJIA and ERA followed by polyarticular JIA were most common subtypes of JIA in our study. Uveitis and ANA positivity were rare findings in our subset of children.

EE194 Economic Evaluation of Tofacitinib for the Treatment of Active Polyarticular Juvenile Idiopathic Arthritis in Greece

EE194 Economic Evaluation of Tofacitinib for the Treatment of Active Polyarticular Juvenile Idiopathic Arthritis in Greece

Identification of key biomarkers in RF-negative polyarticular and oligoarticular juvenile idiopathic arthritis by bioinformatic analysis

ObjectiveJuvenile idiopathic arthritis (JIA) is a broad term used to describe arthritis of unknown origin. JIA commonly persists into adulthood, often causing substantial morbidity such as restricted joint function, which can lead to challenges in employment and independence. This study aims to identify diagnostic biomarkers and investigate the role of immune cells in the pathogenesis of rheumatoid factor-negative polyarticular juvenile idiopathic arthritis (RF-negative pJIA) and oligoarticular juvenile idiopathic arthritis (oJIA).MethodsWe retrieved a JIA dataset from the GEO database and conducted an analysis of differentially expressed genes (DEGs). Subsequently, functional enrichment analysis was performed on the DEGs. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key modules. Additionally, we constructed a protein‒protein interaction network to identify hub genes that serve as signature genes. Furthermore, we employed CIBERSORT to classify immune cell infiltration.ResultsFrom the GSE20307 dataset, we identified a total of 1438 DEGs in RF-negative pJIA and 688 DEGs in oJIA. WGCNA clustered the data into 6 modules in pJIA and 4 modules in oJIA. Notably, the ME5 and ME2 modules exhibited significant associations with pJIA and oJIA, respectively. In both pJIA and oJIA, we identified six hub genes, four of which demonstrated high diagnostic sensitivity and specificity in pJIA, while five showed high diagnostic sensitivity and specificity in oJIA. CIBERSORT analysis suggested the potential involvement of these signature genes in immune cell infiltration.ConclusionIn this study, we identified JUN, CXCL8, SOCS3, and KRAS as biomarkers for RF-negative pJIA and JUN, CXCL8, SOCS3, PTGS2, and NFKBIA as biomarkers for oJIA. Furthermore, our findings suggest that Tfh cells may play a role in the early onset of both RF-negative pJIA and oJIA.

Safety and Effectiveness of Tofacitinib in Treating Polyarticular Course Juvenile Idiopathic Arthritis.

Polyarticular course juvenile idiopathic arthritis (pcJIA) is a form of arthritis that affects at least five joints at a time and presents before the age of 16. Its most common symptoms are pain, swelling, redness, and a limited range of motion, making it incredibly difficult for patients diagnosed to function in daily life. Historically, the leading treatment options have consisted of non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. However, these drugs have serious toxic side effects associated with long-term use in addition to being ineffective in refractory cases. Recently, small molecule biologics have emerged as an alternate treatment to pcJIA. Tofacitinib is a small molecule JAK inhibitor that blocks the JAK/STAT cascade and decreases the transcription of genes responsible for immune function. We conducted a risk-benefit analysis to determine the viability of tofacitinib as a treatment for pcJIA. In our review, we found the side effect profile of tofacitinib to be relatively mild, with many of the serious adverse side effects occurring in those immunocompromised and those with impaired renal and hepatic metabolism. Overall, we have determined that tofacitinib has the potential to be effective in reducing flare-ups and lowering erythrocyte sedimentation rate (ESR) in immunocompetent patients with pcJIA. Additionally, our review has found that tofacitinib has the potential to be effective in patients who are refractory to traditional treatment. However, large-scale clinical trials are needed to determine if this effect holds true in younger pediatric populations, as limited data surrounds this demographic.

Monogenic variants in Laccase domain-containing1 (LACC1) as the cause of juvenile arthritis

Monogenic mutations in laccase domain-containing 1 (LACC1) are associated with clinical pictures that mimic severe courses of polyarticular or systemic juvenile idiopathic arthritis. The diseases are characterized by an early onset during the first year of life, afamilial clustering and ahigh inflammatory activity. The courses are mostly difficult to influence and often lead to sequelae. In this article four cases from two families are presented in which the homozygous mutation p.T276fs* in LACC1 was detected. The children initially suffered from polyarticular or systemic forms of juvenile arthritis. Of the patients two are currently being treated with tocilizumab and methotrexate and one female patient without a basis treatment is currently only receiving local repeated intra-articular steroids. A fourth female patient underwent an allogeneic bone marrow transplantation due to arelapse of an acute lymphatic leukemia. Since then, no further inflammatory symptoms have occurred. The cases presented are compared with the other 50courses published to date. In addition, recent studies investigating the influence of LACC1 mutations, particularly on macrophage function, are summarized.

Aqua-Plyometric Exercises-Induced Changes in Muscle Strength, Bone Mineral Properties, and Physical Fitness in Patients With Juvenile Idiopathic Arthritis: A 12-Week, Randomized Controlled Trial.

To determine whether a 12-week, lower body-targeted aqua-plyometric (AquaPlyo) exercise program could improve muscle strength, bone mineral properties, and physical fitness in patients with juvenile idiopathic arthritis. A randomized controlled trial was adopted and included 48 patients with polyarticular juvenile idiopathic arthritis (age: 12-18y). Patients were assigned to undergo either AquaPlyo exercises (AquaPlyo group, n = 24) or standard exercises (control group, n = 24). The outcome measures were assessed pretreatment and posttreatment and included concentric quadriceps peak torque, bone mineral properties (areal bone mineral density [BMD], volumetric BMD, bone mineral content, and BMD Z score), and physical fitness. A significant posttreatment increase in the concentric quadriceps peak torque was detected in the AquaPlyo group compared with the control group (either at an angular velocity of 90°/s [right side: P = .016, left side: P = .025] or 180°/s [right side: P = .007, left side: P = .029]). Besides, a considerably greater improvement in the areal BMD (P = .0006), volumetric BMD (P = .027), bone mineral content (P = .002), and BMD Z score (P = .0004) was observed in the AquaPlyo group. Moreover, a remarkably greater rise in the physical fitness (P < .001) was revealed in the AquaPlyo group. AquaPlyo training can efficiently enhance muscle strength, improve bone mineral properties, and boost physical fitness in patients with juvenile idiopathic arthritis.

Comparison of Biopsychosocial Characteristics of Children with Juvenile Idiopathic Arthritis According to Common Disease Subtypes.

In this study, we assessed the functional and biopsychosocial characteristics of juvenile idiopathic arthritis (JIA) patients according to disease subtypes. Child Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Disease Activity Score-71 (JADAS-71), and Juvenile Arthritis Biopsychosocial Questionnaire (JAB-Q) scales were administered to 304 JIA patients, and the subscale of JAB-Q was administered to their families. The median age of JIA patients at diagnosis was 7.9 (5.5-13) years (female/male = 1.3). Most patients were under treatment (68.7%) and had inactive disease (69.3%). While there was no significant difference between JADAS-71 scores according to the JIA subtypes, total CHAQ scores in polyarticular JIA patients were higher than in systemic JIA patients (P = .005). Enthesitis-related arthritis (ERA) patients had higher JAB-Q fatigue total scores compared to systemic JJIA patients (P = .001). Juvenile Arthritis Biopsychosocial Questionnaire-child psychosocial status scores were higher in polyarticular JIA patients than oligoarticular and systemic JIA patients (P = .004 and P = .003, respectively), and they had higher JAB-Q child form total scores than systemic JIA patients (P = .006). In addition, systemic JIA patients' parents had higher JAB-Q family total scores compared to oligoarticular JIA patients' parents (P = .03). Our results suggest that polyarticular JIA patients had higher CHAQ, JAB-Q psychosocial status, and child form total scores, and the JAB-Q fatigue score was higher in ERA patients. Also, JAB-Q-parent scores were higher in systemic JIA patients' parents. Biopsychosocial characteristics should be evaluated in both JIA patients and their parents.

Interleukin 6: at the interface of human health and disease.

Interleukin 6 (IL-6) is a pleiotropic cytokine executing a diverse number of functions, ranging from its effects on acute phase reactant pathways, B and T lymphocytes, blood brain barrier permeability, synovial inflammation, hematopoiesis, and embryonic development. This cytokine empowers the transition between innate and adaptive immune responses and helps recruit macrophages and lymphocytes to the sites of injury or infection. Given that IL-6 is involved both in the immune homeostasis and pathogenesis of several autoimmune diseases, research into therapeutic modulation of IL-6 axis resulted in the approval of a number of effective treatments for several autoimmune disorders like neuromyelitis optica spectrum disorder (NMOSD), rheumatoid arthritis, juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis (GCA), and cytokine release syndrome, associated with SARS-CoV2 pneumonia. This review discusses downstream inflammatory pathways of IL-6 expression and therapeutic applications of IL-6 blockade, currently investigated for the treatment of several other autoimmune conditions such as autoimmune encephalitis, autoimmune epilepsy, as well as myelin oligodendrocyte glycoprotein associated demyelination (MOGAD). This review further highlights the need for clinical trials to evaluate IL-6 blockade in disorders such neuropsychiatric lupus erythematosus (SLE), sarcoidosis and Behcet's.