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Life (Basel, Switzerland) May 2024(1) Background: Achieving inactive disease decreases long-term joint damage in patients with polyarticular juvenile idiopathic arthritis (polyJIA). The aim of our study...
(1) Background: Achieving inactive disease decreases long-term joint damage in patients with polyarticular juvenile idiopathic arthritis (polyJIA). The aim of our study was to describe average time to treatment and medication changes over time. (2) Methods: Incident polyJIA patients were retrospectively identified in the InGef and WIG2 longitudinal health claims databases. Drug escalation level changes were evaluated longitudinally and cross-sectionally across three years, as follows: no treatment, glucocorticoids (GCs) and/or non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and biological disease-modifying antirheumatic drugs (bDMARDs). (3) Results: On average, newly diagnosed polyJIA patients received their first csDMARD prescription after 128 days and their first bDMARD prescription after 327 days. More patients were treated with csDMARDs than with bDMARDs at diagnosis; however, 24% and 12% (InGef and WIG2 databases, respectively) had no JIA treatment. After three years, 45% and 31% were not taking any treatments, while 18% and 36% were prescribed bDMARDs. Among patients initiating bDMARDs, most continued treatment for three years, with some switching to csDMARDs or discontinuing treatment. Patients treated only with csDMARDs took them longer, compared to those additionally taking other DMARDs. Patients treated with bDMARDs took them about twice as long as the csDMARDs they took prior. (4) Conclusion: A substantial number of patients with polyJIA are not treated as intensively as guidelines recommend.
PubMed: 38929695
DOI: 10.3390/life14060712 -
Children (Basel, Switzerland) Jun 2024an accurate assessment of the immunity against SARS-CoV-2 can facilitate a better understanding and management of not only the recent coronavirus but similar pathogens...
Application of Interferon-γ Release Assay in the Assessment of T-Cell Immunity to SARS-CoV-2 Antigens in the Cohort of Pediatric Patients with Juvenile Idiopathic Arthritis.
an accurate assessment of the immunity against SARS-CoV-2 can facilitate a better understanding and management of not only the recent coronavirus but similar pathogens as well. the aim of this study was to evaluate T-cell immunity with reference to antibody titers in a group of pediatric patients with autoimmune arthritides utilizing the widely known Interferon-γ Release Assay (IGRA). This study was conducted in the cohort of 55 children suffering from Juvenile Idiopathic Arthritis (JIA). This research analyzed the SARS-CoV-2 T-cell response measured by a specific quantitative IGRA, followed by a serological ELISA test measuring the presence and quantity of IgG, IgM, and IgA antibodies in serum. The cellular response to SARS-CoV-2 measured by the IGRA test significantly correlated with the antibody titers, IgA ( < 0.00003, R = 0.537), IgG ( < 0.0001, R = 0.668), and IgG nucleocapsid protein (NCP) ( < 0.003, R = 0.0399), with no correlation with IgM levels. The antibody levels in patients receiving biological agents were significantly lower compared to the rest of the cohort ( = 0.0369), while traditional disease-modifying antirheumatic drugs had no such effect. the main limitation of the research is the small sample size, mostly due to the specific cohort of patients and the lack of a healthy control. IGRA appears to be a viable tool in the accurate evaluation of T-cell responses to SARS-CoV-2, and serodiagnostics alone is not always sufficient in the assessment of immune responses.
PubMed: 38929315
DOI: 10.3390/children11060736 -
Biomedicines Jun 2024T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases,...
T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases, including Juvenile Idiopathic Arthritis (JIA). The molecular mechanisms underlying T cell activation are still incompletely understood. T cell activation promotes the acetylation of histone 3 at Lysine 27 (H3K27ac) at enhancer and promoter regions of proinflammatory cytokines, thereby increasing the expression of these genes which is essential for T cell function. Co-activators E1A binding protein P300 (P300) and CREB binding protein (CBP), collectively known as P300/CBP, are essential to facilitate H3K27 acetylation. Presently, the role of P300/CBP in human CD4+ T cells activation remains incompletely understood. To assess the function of P300/CBP in T cell activation and autoimmune disease, we utilized iCBP112, a selective inhibitor of P300/CBP, in T cells obtained from healthy controls and JIA patients. Treatment with iCBP112 suppressed T cell activation and cytokine signaling pathways, leading to reduced expression of many proinflammatory cytokines, including IL-2, IFN-γ, IL-4, and IL-17A. Moreover, P300/CBP inhibition in T cells derived from the inflamed synovium of JIA patients resulted in decreased expression of similar pathways and preferentially suppressed the expression of disease-associated genes. This study underscores the regulatory role of P300/CBP in regulating gene expression during T cell activation while offering potential insights into the pathogenesis of autoimmune diseases. Our findings indicate that P300/CBP inhibition could potentially be leveraged for the treatment of autoimmune diseases such as JIA in the future.
PubMed: 38927552
DOI: 10.3390/biomedicines12061344 -
Arthritis Research & Therapy Jun 2024Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA).
METHODS
Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months.
RESULTS
At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25-5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48-9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03-8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02-5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57-5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23-5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46-9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76-7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07-3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10-4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15-8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders.
CONCLUSION
Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.
Topics: Humans; Abatacept; Arthritis, Juvenile; Male; Female; Child; Biomarkers; Antirheumatic Agents; Calgranulin B; Adolescent; Treatment Outcome; Child, Preschool; Calgranulin A; S100A12 Protein; S100 Proteins
PubMed: 38918871
DOI: 10.1186/s13075-024-03347-0 -
Reumatismo Jun 2024The indices to measure disease activity of chronic arthritis in adulthood and childhood are different. Therefore, assessing the status of the disease in young patients...
OBJECTIVE
The indices to measure disease activity of chronic arthritis in adulthood and childhood are different. Therefore, assessing the status of the disease in young patients with juvenile idiopathic arthritis (JIA) can be tricky, especially when the transition to adult care is ongoing. The aim of our study was to assess the level of correlation between adult and juvenile scores in the measurement of disease activity in JIA patients during transitional care.
METHODS
We estimated the disease activity by using the Juvenile Arthritis Disease Activity Score 71 (JADAS71), clinical JADAS, adult Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in JIA patients in transitional care. We enrolled patients older than 16 years at the time of the first transition visit, and disease activity was assessed at baseline and 12 months. Regression analyses were carried out to estimate the level of agreement among the different indices.
RESULTS
We recruited 26 patients with JIA; 11 patients were polyarticular (42.3%) and 15 patients were oligoarticular (53.1%). The mean age at diagnosis was 7.7±3.9 years and the age at the first evaluation was 20.9±3.7 years. The correlation between JADAS71 and DAS28 was r2=0.69, r2=0.86 between JADAS71 and SDAI, and r2=0.81 between JADAS71 and CDAI.
CONCLUSIONS
SDAI and JADAS71 showed the best correlation, but a few patients were not captured at the same level of disease activity. New prospective studies with a larger number of patients will be needed in this field.
Topics: Humans; Arthritis, Juvenile; Female; Male; Severity of Illness Index; Transition to Adult Care; Child; Adolescent; Young Adult; Adult
PubMed: 38916167
DOI: 10.4081/reumatismo.2024.1638 -
Pediatric Investigation Jun 2024Systemic lupus erythematosus (SLE) is a diffuse connective tissue disease with complex clinical manifestations and prolonged course. The early diagnosis and condition...
IMPORTANCE
Systemic lupus erythematosus (SLE) is a diffuse connective tissue disease with complex clinical manifestations and prolonged course. The early diagnosis and condition monitoring of SLE are crucial to disease prognosis.
OBJECTIVE
To assess the diagnostic value of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in childhood-onset SLE (cSLE).
METHODS
Fifty-seven children diagnosed with SLE, 40 children diagnosed with juvenile idiopathic arthritis (JIA), and 40 healthy children were included. Peripheral blood samples from each patient were collected. A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood. Associations among parameters were analyzed using the Mann-Whitney test or independent sample -test.
RESULTS
The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA. Receiver operating characteristic curves revealed an area under the curve (AUC) of 0.633 (95% confidence interval [CI], 0.524-0.742; = 0.024) for lncNEAT1_1. The AUC of lncNEAT1_2 was 0.812 (95% CI, 0.727-0.897; < 0.0001) to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925. Moreover, lncNEAT1_2 expression was higher in patients with cSLE presenting with fever, lupus nephritis, elevated erythrocyte sedimentation rate, active disease activity, and decreased C3 level, compared with those without these conditions. However, no similar correlation was observed for lncNEAT1_1.
INTERPRETATION
The expression of lncNEAT1_2 was significantly elevated in children with SLE, especially those with fever, renal involvement, and low C3 levels. These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.
PubMed: 38910848
DOI: 10.1002/ped4.12413 -
Journal of Nippon Medical School =... Jun 2024Mixed connective tissue disease (MCTD) is characterized by mixed features of systemic lupus erythematosus, systemic sclerosis, and polymyositis/dermatomyositis and is...
Mixed connective tissue disease (MCTD) is characterized by mixed features of systemic lupus erythematosus, systemic sclerosis, and polymyositis/dermatomyositis and is rare in children. Here, we report a case of MCTD in a 10-year-old girl who presented at our hospital with arthralgia, Raynaud's phenomenon, and fatigue. Blood tests were positive for anti-U1-ribonucleoprotein (RNP) antibodies and for rheumatoid factors (RFs) IgG-RF and anti-galactose-deficient IgG. Levels of myogenic enzymes and hypergammaglobulinemia were elevated. Macrophages were prominent in bone marrow, with scattered phagocytic macrophages. MCTD was diagnosed based on the patient's symptoms and laboratory findings. Methylprednisolone pulse therapy combined with oral tacrolimus was administered, which led to resolution of symptoms. Three months after pulse therapy, arthralgia worsened and methotrexate was administered. Arthralgia improved but did not resolve. Magnetic resonance imaging performed to investigate the hip pain revealed a mature ovarian teratoma, which was surgically removed. Because the pain persisted and interfered with her daily life, she was treated with tocilizumab for joint pain relief, which decreased the pain level. Tocilizumab is a candidate for additional treatment of juvenile idiopathic arthritis-like arthritis associated with childhood-onset MCTD.
PubMed: 38897945
DOI: 10.1272/jnms.JNMS.2025_92-303 -
Asian Journal of Surgery Jun 2024
PubMed: 38897832
DOI: 10.1016/j.asjsur.2024.05.197 -
Frontiers in Pediatrics 2024To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).
OBJECTIVES
To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA).
METHODS
A total of 40 pediatric patients, 20 (50%) with JIA and 20 (50%) healthy control subjects, were studied, and performed the renal function on 24-h collection and the 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we compared renal function and blood pressure trends between the groups of JIA patients with different disease activities.
RESULTS
No statistically significant differences were observed between patients with JIA and healthy children in terms of glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tubular reabsorption of phosphate (TRP), and calcium-creatinine urine ratio (CaU/CrU). In contrast, we observed significantly higher values in JIA patients than in controls for the presence of hematuria ( < 0.0001) and proteinuria ( < 0.0001). Compared to the control group there were significantly higher values of hematuria and proteinuria/day in both groups of JIA patients with low disease activity (respectively, = 0.0001 and = 0.0002) and moderate disease activity (respectively = 0.0001 and = 0.0012). Systolic and diastolic dipping were significantly reduced in patients with JIA compared with healthy controls ( < 0.0001 and < 0.0001, respectively).
CONCLUSIONS
Our study showed that children with JIA, already in the early stages of the disease, have higher values of hematuria and proteinuria, which are early warning signs of nephropathy. Therefore, detailed screening of renal function and pressure monitoring in patients are necessary to monitor their evolution over time.
PubMed: 38895193
DOI: 10.3389/fped.2024.1395961 -
Pediatric Rheumatology Online Journal Jun 2024
Correction: The risk of depression and anxiety is not increased in individuals with juvenile idiopathic arthritis - results from the south-Swedish juvenile idiopathic arthritis cohort.
PubMed: 38886800
DOI: 10.1186/s12969-024-00995-z