Juvenile Idiopathic Arthritis Disease Research Articles

Biomarker Changes in Response to Tofacitinib Treatment in Patients with Polyarticular Course Juvenile Idiopathic Arthritis.

Examine levels of candidate blood-based biomarkers (CBB) in juvenile idiopathic arthritis (JIA) treated with tofacitinib. JIA patients who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBB (S100A8/9, S100A12, IL-18, SAA, resistin, VEGF, Angiopoietin-1, Angiopoietin-2, MMP8, MMP2, TIMP1, Leptin, CXCL9, sIL2R, ICAM-1, sTNFr, IL-6, IL-23, MCP1, CCL18, and CCL20). Association of CBB with JIA response to treatment from baseline to week 18 were assessed. This study included 166 patients with polyarticular-course JIA. Paired serum samples from 143 patients were available at both baseline and week 18. There were 35% (50/143) of patients with a JIA-American College of Rheumatology 90 (JIA-ACR90) level improvement while 90/121/137 (63%/85%/96%) achieved JIA-ACR70/50/30 improvement at wk18. Despite small numerical differences by JIA category, there were no baseline CBB values that independently predicted a decrease in JADAS-27 or JIA-ACR90 response by week 18. Decrease in resistin level (baseline to week 18) was significantly associated with wk18 improvement in JADAS-27 and JIA-ACR90 response, after adjusting for age, sex, JIA disease duration and baseline resistin [(r2 0.79, SE, 0.070, p<0.01 and OR(95%CI) = 1.134(1.018,1.264)]. HLA-B27 positivity was significantly associated with not achieving a JIA-ACR90 response at week 18 (p=0.0097). Among the CBB included, only resistin was significantly associated with treatment response, and no CBB was identified that forecasts JIA improvement after initiation of tofacitinib. The association of HLA-B27 positivity with lower response to tofacitinib in JIA is intriguing and merits further study.

Serum hepcidin evaluation as a promising biomarker in juvenile idiopathic arthritis.

An important area of research in juvenile idiopathic arthritis (JIA) aims to identify sensitive and reliable biomarkers of disease activity. The key iron-regulatory hormone hepcidin-25 (HEP) has been advocated as a potential biomarker to assess anaemia of chronic disease and iron deficiency in adults with rheumatoid arthritis. We performed a cross-sectional study evaluating the utility of serum HEP in 79 non-systemic onset JIA patients (14 males, 65 females), with/without anaemia, determining its correlations with disease activity, assessed by the JIA Disease Activity Score (JADAS)-27, anaemia parameters, and iron status indices. Significant positive correlations for serum HEP levels were found with the JADAS-27 score (r=0.8988, p<0.0001), and significant differences were found in HEP serum levels between active and inactive patients (8.6 IQR 10.0 ng/mL vs. 2.9 IQR 1.9 ng/mL; p<0.0001). Mean serum HEP concentrations were significantly greater in high disease activity group than in others (p<0.0001). At the ROC curve, an HEP level >4.35 ng/mL discriminated subjects with active disease with a sensitivity of 91.8% and a specificity of 80.0% (AUC: 0.93; 95% CI: 0.88-0.98). Moreover, HEP levels were significantly higher in anaemic, iron repleted and active disease patients. HEP is associated with JIA disease activity, and it could be useful in early detection and monitoring of disease exacerbations. These findings highlight that inflammation plays a major role in HEP induction and point out that HEP could be directly implicated in the JIA inflammatory cascade.

Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study

ObjectivesWe report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study.MethodsPatients (2–<18 years) with JIA who completed phase...

Validation of new medication use algorithms as proxies for worsening disease activity in patients with juvenile idiopathic arthritis.

To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity. Using electronic health record data from three pediatric centers, we defined new JIA medication use as (re)initiation of disease-modifying antirheumatic drugs or glucocorticoids (oral or intra-articular). Data were collected from 201 randomly selected subjects with (101) or without (100) new medication use. We assessed the positive predictive value (PPV) and negative predictive value (NPV) based on a reference standard of documented worsening of JIA disease activity. The algorithm was refined to optimize test characteristics. Overall, the medication-based algorithm had suboptimal performance in representing worsening JIA disease activity (PPV 69.3%, NPV 77.1%). However, algorithm performance improved for definitions specifying longer times after JIA diagnosis (≥1-year post-diagnosis: PPV 82.9%, NPV 80.0%) or after initiation of prior JIA treatment (≥1-year post-treatment: PPV 89.7%, NPV 80.0%). An algorithm for new JIA medication use appears to be a reasonable proxy for worsening JIA disease activity, particularly when specifying new use ≥1 year since initiating a prior JIA medication. This algorithm will be valuable for conducting research on JIA populations within administrative claims databases.

Serum and salivary inflammatory biomarkers in juvenile idiopathic arthritis—an explorative cross-sectional study

BackgroundBiomarkers may be useful in monitoring disease activity in juvenile idiopathic arthritis (JIA). With new treatment options and treatment goals in JIA, there is an urgent need for more sensitive and responsive biomarkers.ObjectiveWe aimed to investigate the patterns of 92 inflammation-related biomarkers in serum and saliva in a group of Norwegian children and adolescents with JIA and controls and in active and inactive JIA. In addition, we explored whether treatment with tumor necrosis factor inhibitors (TNFi) affected the biomarker levels.MethodsThis explorative, cross-sectional study comprised a subset of children and adolescents with non-systemic JIA and matched controls from the Norwegian juvenile idiopathic arthritis study (NorJIA Study). The JIA group included individuals with clinically active or inactive JIA. Serum and unstimulated saliva were analyzed using a multiplex assay of 92 inflammation-related biomarkers. Welch’s t-test and Mann–Whitney U-test were used to analyze the differences in biomarker levels between JIA and controls and between active and inactive disease.ResultsWe included 42 participants with JIA and 30 controls, predominantly females, with a median age of 14 years. Of the 92 biomarkers, 87 were detected in serum, 73 in saliva, and 71 in both biofluids. A pronounced difference between serum and salivary biomarker patterns was found. Most biomarkers had higher levels in serum and lower levels in saliva in JIA versus controls, and in active versus inactive disease. In serum, TNF and S100A12 levels were notably higher in JIA and active disease. The TNF increase was less pronounced when excluding TNFi-treated individuals. In saliva, several biomarkers from the chemokine family were distinctly lower in the JIA group, and levels were even lower in active disease.ConclusionIn this explorative study, the serum and salivary biomarker patterns differed markedly, suggesting that saliva may not be a suitable substitute for serum when assessing systemic inflammation in JIA. Increased TNF levels in serum may not be a reliable biomarker for inflammatory activity in TNFi-treated children and adolescents with JIA. The lower levels of chemokines in saliva in JIA compared to controls and in active compared to inactive disease, warrant further investigation.

Tumor-necrosis factor α-rich environment alters type-I interferon response to viral stimuli in patients with juvenile idiopathic arthritis by altering myeloid dendritic cell phenotype

The balance between the tumor-necrosis factor α (TNFα) and type-I interferon (T1IFN) pathways is crucial for proper immune function. Dysregulation of either pathway can contribute to autoimmune diseases development. Even though TNFα blockade has shown promising results in various autoimmune diseases, the effect on the balance between TNFα and T1IFN is elusive. We used targeted anti-TNFα therapies in juvenile idiopathic arthritis (JIA) as an experimental approach to study the cross-regulation between TNFα and type-I IFN. We found that TNFα-rich environment affected viral defense through the attenuation of T1IFN responses and affected the phenotype and distribution of myeloid dendritic cells, which are engaged in early viral infections. Anti-TNFα therapy normalized the observed deviations in JIA patients. We hypothesize that the inadequate immune response caused by a high TNFα environment could be projected to more frequent or lengthy viral infections and possibly play a role in the process of JIA disease development.

Serum immunoglobulin A (IgA) levels in children affected with Juvenile Idiopathic Arthritis

Background and objectiveImmunoglobulin A (IgA) is the most abundant antibody isotype in the human body, considering its presence on the mucosal surfaces, in addition to the amount circulating in the bloodstream. Serum IgA levels can be variably altered in several pathological settings. However, very few studies specifically investigated serum IgA in Juvenile Idiopathic Arthritis (JIA). In the present study, we specifically assessed serum IgA levels in our cohort of patients affected with JIA. MethodsIn this cross-sectional study, serum IgA levels were measured in patients with JIA (and age-matched controls) and analyzed according to age class. The correlation of serum IgA levels with hematological, inflammatory, and disease activity parameters was assessed. ResultsNo significant difference in the frequency of low IgA levels (according to the definition of complete and partial IgA deficiency) was observed between JIA patients and controls, overall. This pediatric study population showed a progressive increase of total serum IgA concentrations with age, as expected; however, in JIA patients aged 10–17 years, total IgA serum levels resulted to be significantly higher than in age-matched control subjects. No clear correlation between IgA levels and the examined inflammatory, hematological, and disease activity parameters was observed in JIA patients, except for the erythrocyte sedimentation rate (ESR) in oligoarticular JIA patients: here, serum IgA levels showed a positive and moderate covariation with ESR, which was also observed for disease activity (JADAS-10) in selected oJIA patients without biological therapy. ConclusionsIn our cohort of JIA patients, total serum IgA levels were not reduced and were actually increased in adolescents compared to controls. Larger studies are needed to confirm this finding, which cannot be certainly explained based on the available data in this study, even though JIA disease control and/or chronic inflammation may be implicated to some extent.

Psychiatric Morbidity Is Common Among Children With Juvenile Idiopathic Arthritis: A National Matched Cohort Study.

Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease that causes joint inflammation and pain. Previous studies have indicated affected mental health and increased risk of psychiatric conditions among patients with JIA. We aimed to explore differences in psychiatric morbidity between children with JIA and their peers. We further studied if parental socioeconomic status (SES) influences the association between JIA and the risk of psychiatric morbidity. We used a matched cohort design to estimate the association between JIA and psychiatric disease. Children with JIA, born between 1995 and 2014, were identified in Danish national registers. Based on birth registers, we randomly selected 100 age- and sex-matched children per index child. Index date was the date of the fifth JIA diagnosis code or the date of matching for reference children. End of follow-up was the date of psychiatric diagnosis, death, emigration, or December 31, 2018, whatever came first. Data were analyzed using a Cox proportional hazard model. We identified 2086 children with JIA with a mean age at diagnosis of 8.1 years. Children with JIA had a 17% higher instantaneous risk of a psychiatric diagnosis when compared with the reference group, with an adjusted hazard ratio of 1.17 (95% CI 1.02-1.34). Relevant associations were found only for depression and adjustment disorders. Stratifying our analysis for SES showed no modifying effect of SES. Children with JIA had a higher risk of psychiatric diagnoses compared to their peers, especially diagnoses of depression and adjustment disorders. The association between JIA and psychiatric disease did not depend on parental SES.

Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.

Although interleukin-1 (IL-1)/IL-6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL-1/IL-6 inhibitor-exposed patients with systemic JIA. Among JIA patients at our institution exposed to interleukin-1 (IL-1)/IL-6 inhibitors (1995-2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL-1/IL-6 inhibitors, other cytokine inhibitors, methotrexate). We used Cox models to identify predictors of eosinophilia during IL-1/IL-6 inhibitor use and summarized treatment changes and outcomes after eosinophilia, including lung disease. HLA typing was performed on a clinical or research basis. There were 264 new medication exposures in 75 patients with systemic JIA and 41 patients with other JIA. A total of 49% of patients with systemic JIA with HLA typing (n=45) were positive for HLA-DRB1*15 alleles. Eosinophilia was common during IL-1/IL-6 inhibitor use and did not differ by systemic JIA compared to other JIA (0.08 and 0.07 per person-year, respectively; P=0.30). Among systemic JIA patients, pretreatment macrophage activation syndrome (MAS) was associated with a higher rate of subsequent eosinophilia on biologic therapy (unadjusted hazard ratio 3.2 [95% confidence interval 1.2-8.3]). A total of 4 of 5 patients who switched therapy within 10 weeks of eosinophilia experienced disease flare compared to none of the patients who continued the original therapy. A total of 8 of 25 patients with pulmonary evaluations had lung disease, and all had severe manifestations of systemic JIA (MAS, intensive care unit stay). One death was attributed to systemic JIA-lung disease. Eosinophilia is common in JIA patients using IL-1/IL-6 inhibitors. Severe disease may be associated with eosinophilia and lung disease in systemic JIA.

HLA-DRB1*15 and Eosinophilia Are Common Among Patients With Systemic Juvenile Idiopathic Arthritis.

Concern exists that medications used to treat patients with systemic juvenile idiopathic arthritis (JIA), particularly interleukin (IL)-1 and IL-6 blocking agents, might be causing adverse drug reactions and lung disease (systemic JIA-LD). Carriage of HLA-DRB1*15 has been reported as a risk factor for adverse drug reactions among patients with systemic JIA. We performed a retrospective chart review to evaluate these factors at our center. We reviewed the records of 86 subjects with systemic JIA followed for at least 6 months between 1996 and 2022. HLA typing was performed in 23 of the subjects. We compared characteristics of patients with or without eosinophilia. Among patients with HLA typing, we compared clinical characteristics of subjects with or without DRB1*15 and with or without systemic JIA-LD. Among the 23 patients with HLA typing, 74% carried DRB1*15, and 63% of patients without systemic JIA-LD carried DRB1*15. Seven subjects had systemic JIA-LD, all of whom carried DRB1*15. Patients with systemic JIA-LD were younger at the time of diagnosis and more likely to have had macrophage activation syndrome. Exposure to IL-1 and IL-6 blockers was common, occurring in 95% of patients. Eosinophilia occurred in 39% of patients with systemic JIA, often before IL-1 or IL-6 blockade. Eosinophilia was associated with adverse drug reactions and macrophage activation syndrome. There was 1 death, unrelated to active systemic JIA disease. Carriage of DRB1*15 was more common in this cohort of patients with systemic JIA than in the general population. Eosinophilia and systemic JIA-LD were more common among patients with severe systemic JIA complicated by macrophage activation syndrome.

Serum calprotectin and joint ultrasound in the definition of disease relapse in non-systemic juvenile idiopathic arthritis: a prospective longitudinal study.

The aim of our study was to investigate the role of serum calprotectin (SC) and muscle-skeletal ultrasound (MSUS) as predictive markers of relapse in patients with juvenile idiopathic arthritis (JIA). Sixty non-systemic (ns) JIA patients in clinical remission were recruited to evaluate the risk of disease relapse. SC levels and JIA disease activity were assessed at every visit (3, 6, 12 and 18 months). Joint synovitis, characterised by both synovial effusion (SE) and synovial hyperplasia (SH), was measured by US score (sum of SE, SH, power Doppler and bone erosions) given to each examined joint and US ratio (US score/number of joints examined) at every visit. Associations of SC, US score and US ratio with relapse prevalence was studied longitudinally by using generalised estimating equations model. Thirty-one (51.6%) patients relapsed within 18 months. Patients with higher baseline US scores showed higher risk of relapse at 6 months (OR (95% confidence interval (CI)): 1.96 (1.09-3.52)). Additionally, patients with higher SC values at baseline showed higher risk of relapse at 18 months (1.66 (1.13-2.44)). Patients with higher baseline SC values showed an increased overall odds of relapse up to 18 months of follow-up (1.21 (1.08-1.36)). Furthermore, patients with higher US scores showed an increased overall odds of relapse up to 18 months of follow-up (1.96 (1.56-2.46)). Similarly, patients with higher US ratio showed an increased overall odds of relapse up to 18 months of follow-up (16.62 (7.17-38.54)). SC was able to identify JIA patients with unstable remission and increased risk of relapse. MSUS represents an interesting additional tool to the clinical evaluation, especially in predicting early relapse.

Assessment of bone mineral density and bone turnover markers in patients with juvenile idiopathic arthritisy

Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory diseases occurring in childhood, associated with decreased bone mineral density (BMD) and increased risk of osteopenia and osteoporosis, which increases the fracture risk. Aim of the work: to assess BMD and bone turnover markers (serum osteocalcin for bone formation and C terminal telopeptide of type 1 collagen for bone resorption) in JIA patients and their relation to disease activity. This study included 50 patients with JIA (female:male – 20:30). The study was approved by the Ethical Research Committee and Institutional Review Board of the Faculty of Medicine, Menoufia University, Egypt (Approval number: 19519INTPH48). Written informed consent was obtained from each patient or the parents. These patients were diagnosed with JIA according to the criteria of classification of the International League of Associations for Rheumatology. BMD was measured by Dual-energy X-ray absorptiometry (DEXA) of the lumbar spine using the Z-score. The results were correlated with JIA disease duration, disease activity, bone turnover markers and serum level of vitamin D. Clinical disease activity was evaluated by juvenile arthritis disease activity score (JADAS-27). There was a significant negative correlation between DEXA Z-score and disease activity (p-value &lt; 0.001), bone turnover markers (p-value &lt; 0.001), and duration of JIA (p-value &lt; 0.05). There was a significant difference between vitamin D level and DEXA Z-score; DEXA Z-score was lower in vitamin D deficient patients. JIA patients with higher disease activity are at a higher risk of osteopenia and osteoporosis. Well-timed and efficient treatment of JIA and proper control of disease activity may help to improve the bone status and reduce the incidence of osteoporosis. Consequently, valuable targeted interventions are essential to preserve bone health during JIA.

Active disease in juvenile idiopathic arthritis: current patterns and associations: a one-year study

Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic ailment of children. JIA is characterized by idiopathic peripheral arthritis with an immunoinflammatory pathogenesis possibly activated by contact with external antigens. To describe the success of active disease (AD) and remission in polyarticular juvenile idiopathic arthritis (JIA) and to measure the associations among patient characteristics, imaging results and these outcomes. The aim of this study is to assess the Active disease in juvenile idiopathic arthritis: current patterns and associations. Methods: This is an observational study. The study used to be carried out in the admitted patient’s Department of pediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh. In Bangladesh for the duration of the period from October 2015 to March 2017. Results: This study shows that the according to age of 33 patients aged 1 to 9 years. Here according to age distribution, 2 (6.1%) were 1-3 years, 10 (30.30%) were &gt;3‑6 years, 9 (27.27%) were &gt;6-9 years and 12 (36.4%) were &gt;9 years. And according to gender 13 (39.4%) were male and 20 (60.6%) were female. Conclusions: Children with polyarticular JIA spent the majority of their follow-up with active disease. Because children with early radiographic evidence of joint damage have the most active disease, improving outcomes for these subgroups may be an important goal for prospective study.

Haptoglobin in Juvenile Idiopathic Arthritis

BackgroundHaptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs.MethodsPlasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP).ResultsAt 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001).ConclusionHp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.

Treat to Target (Drug-Free) Inactive Disease in JIA: To What Extent Is This Possible?

Background: Treat to target (T2T) is a strategy that has been increasingly employed in the management of several chronic diseases, with demonstrated improved outcomes. The use of T2T in juvenile idiopathic arthritis (JIA), a common rheumatic disease of childhood, is still in its infancy, and the feasibility of its use in attaining drug-free clinical remission is unclear. Aims: We aim to explore the current literature of the use of T2T in JIA, and to review the potential benefits and limitations of this approach in regard to this chronic disease. Sources: A comprehensive PubMed search was conducted using relevant keywords, with full text articles in English included in the review. Content: T2T is an appealing strategy for improving outcomes of pediatric rheumatic diseases given the limited availability of therapeutics and potential cumulative effects of long-term immunosuppression. The application in a cohort of children, however, is limited by heterogeneity of disease, availability of high-quality evidence, and patient and parental preferences. Unlike adult rheumatoid arthritis, the ‘window of opportunity’ has not been definitively demonstrated in large scale trials, and although early studies of T2T in JIA have been favorable, the timing and means of escalation (especially with regard to biologics) need clarification. Implications: This review outlines several issues of implementing T2T in JIA, including the important extra-articular manifestations of disease and non-pharmacological management, that should be considered in future consensus guidelines.

A novel magnetic resonance imaging scoring system for active and chronic changes in children and adolescents with juvenile idiopathic arthritis of the hip

BackgroundHip involvement predicts severe disease in juvenile idiopathic arthritis (JIA) and is accurately assessed by MRI. However, a child-specific hip MRI scoring system has not been validated.ObjectiveTo test the intra- and interobserver agreement of several MRI markers for active and chronic hip changes in children and young adults with JIA and to examine the precision of measurements commonly used for the assessment of growth abnormalities.Materials and methodsHip MRIs from 60 consecutive children, adolescents and young adults with JIA were scored independently by two sets of radiologists. One set scored the same MRIs twice. Features of active and chronic changes, growth abnormalities and secondary post-inflammatory changes were scored. We used kappa statistics to analyze inter- and intraobserver agreement for categorical variables and a Bland–Altman approach to test the precision of continuous variables.ResultsAmong active changes, there was good intra- and interobserver agreement for grading overall inflammation (kappa 0.6–0.7). Synovial enhancement showed a good intraobserver agreement (kappa 0.7–0.8), while the interobserver agreement was moderate (kappa 0.4–0.5).Regarding acetabular erosions on a 0–3 scale, the intraobserver agreement was 0.6 for the right hip and 0.7 for the left hip, while the interobserver agreement was 0.6 for both hips. Measurements of joint space width, caput–collum–diaphyseal angle, femoral neck–head length, femoral width and trochanteric distance were imprecise.ConclusionWe identified a set of MRI markers for active and chronic changes in JIA and suggest that the more robust markers be included in future studies addressing clinical validity and long-term patient outcomes.

Association between Interleukin-17F 7488A/G and 7383A/G polymorphisms and susceptibility to juvenile idiopathic arthritis

BackgroundInterleukin-17F (IL-17F), one of the cytokines, is crucial in the pathophysiology of juvenile idiopathic arthritis (JIA). Therefore, we aimed to determine the relation between IL17F 7488A/G and IL17F 7383A/G single-nucleotide polymorphisms and JIA susceptibility and to explain their impact on the disease activity.MethodsGenomic DNA of 70 patients with JIA and 70 age and sex-matched controls were extracted and typed for IL17F 7488A/G and IL17F 7383A/G single-nucleotide polymorphisms, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls.ResultsWhen compared to AA participants, children with the AG genotype of the IL17F 7488A/G and IL17F 7383A/G polymorphisms showed a substantially greater risk of JIA. Furthermore, children with the G allele were 2.8 folds more likely to have JIA than the A allele for IL17F 7488A/G polymorphism and 3.72 folds for IL17F 7383A/G polymorphism. Children with AG genotype of IL17F 7383A/G polymorphism were far more likely to have high activity JIA.ConclusionsThe G allele of both IL17F 7488A/G and IL17F7383 A/G polymorphisms is associated with increased JIA susceptibility, and JIA at High Disease Activity was more likely to develop in AG subjects of the IL17F 7383 A/G polymorphism.ImpactThe relationship between Interleukin-17F 7488A/G and 7383A/G polymorphisms and risk for JIA has not been recognized before.Impact of Interleukin-17F 7488A/G and 7383A/G genotypes on JIA disease activity.The G allele of both IL17F 7488A/G and IL17F7383 A/G polymorphisms are associated with increased JIA susceptibility.AG genotype of Interleukin-17F 7383 A/G polymorphism compared to AA patients, had a higher probability of developing JIA at a High Disease Activity (HDA) level.

Are infections in children with juvenile idiopathic arthritis more frequent than in healthy children? A prospective multicenter observational study.

BackgroundChildren with juvenile idiopathic arthritis (JIA) might be at a higher risk of infection. Our objectives are to describe and compare infection rates in patients with JIA vs. healthy patients.MethodsA prospective, multicenter observational study was performed in Spain from January 2017 to June 2019. Patients with JIA from 7 participating hospitals and children without JIA (siblings of patients with JIA, and non-JIA children from primary health centers) were followed up with quarterly questionnaires to record infection episodes. Tuberculosis, herpes zoster, and infections requiring hospital admission were considered severe infections. Rates of infection (episodes/patient/year) were compared using a generalized estimating equations model.ResultsA total of 371 children (181 with and 190 without JIA) were included. The median age was 8.8 years (IQR 5.5–11.3); 75% of the patients with JIA received immunosuppressive treatment (24% methotrexate, 22% biologic, 26% both). A total of 667 infections were recorded; 15 (2.2%) were considered severe. The infection rate was 1.31 (95%CI 1.1–1.5) in JIA and 1.12 (95%CI 0.9–1.3) in non-JIA participants (p = 0.19). Age <4 years increased the infection rate by 2.5 times (2.72 vs. 1.12, p < 0.001) in both groups. The most frequent infection sites were upper respiratory (62.6% vs. 74.5%) and gastrointestinal (18.8% vs. 11.4%). There were no differences in severe infections (2.5% vs. 2%, p = 0.65) between the groups. In children with JIA, younger age and higher disease activity (JADAS71) were associated with a higher infection rate.ConclusionWe found no differences in the infection rate or infection severity between patients with and without JIA. Most infections were mild. An age younger than 4 years increased the infection risk in both groups. Higher disease activity was associated with a higher infection rate.

Psychological/social factors associated with transfer readiness in young people with juvenile idiopathic arthritis

The aim of this study is to investigate the relationships between psychological/social factors and transfer readiness from paediatric to adult rheumatology services in pre- and post-transfer young people (YP) with juvenile idiopathic arthritis (JIA). Participants completed questionnaires measuring a broad range of psychological/social factors (generalised anxiety, pain-specific anxiety, pain-related thoughts, depression, prosocial behaviours, problem behaviours, arthritis-related quality of life (QoL), social support, family functioning) and transfer readiness (transfer-related knowledge and skills, health-related self-efficacy). JIA disease activity was measured on the same day as the questionnaires. This study received all relevant ethical and regulatory approvals, and informed consent was received from or on behalf of all participants. In total, 40 pre-transfer YP with JIA aged 10-16 years (M = 13.54 years, 26 females) and their parents/guardians participated at Sheffield Children's NHS Foundation Trust, and 40 post-transfer YP with JIA aged 16-24 years (M = 20.16 years, 26 females) participated at Sheffield Teaching Hospitals NHS Foundation Trust. For both pre- and post-transfer YP, greater transfer readiness was associated with lower generalised anxiety levels, lower pain-specific anxiety levels, fewer pain-related thoughts, lower depression levels, fewer problem behaviours, better arthritis-related QoL, better social support, and better family functioning. Greater transfer readiness was also associated with less JIA disease activity for post-transfer YP only. A broad range of psychological/social factors were associated with transfer readiness in pre- and post-transfer YP with JIA. This highlights the importance of assessing and addressing YP's psychological/social well-being during their transition to adult services. Key Points • A wide range of psychological and social factors may be associated with how ready young people with juvenile idiopathic arthritis feel to move from paediatric to adult rheumatology services. • Transition outcomes may be improved by comprehensively assessing and addressing young people's psychological and social well-being.

Safety of the BNT162b2 mRNA COVID-19 vaccine in children and adolescents with juvenile idiopathic arthritis: a tertiary-center early experience

BackgroundResearch on the COVID-19 vaccination in patients with underlying rheumatic disorders in pediatric age is lacking. We studied possible adverse events of the mRNA BNT162b2 vaccine against SARS-CoV-2 (Pfizer-BioNTech) in children and adolescents with juvenile idiopathic arthritis (JIA), and also if there is a risk of flaring of the underlying JIA. We reported 36 JIA patients aged 5–18 years old received 2 doses of the COVID-19 vaccine (72 doses). Patients were followed before and after vaccination, and any related adverse event was recorded. JIA disease activity was assessed using Juvenile Arthritis Disease Activity Score-10 (JADAS-10) before and after vaccination.ResultsAmong 72 doses of the vaccine received, local adverse events (AEs) were reported by majority of the patients (66.7%); most commonly reported local AE was pain at the site of injection. Systemic AEs were revealed by (65.3%), most commonly reported systemic AEs were tiredness, myalgia, and headache. Almost all the reported AE were mild to moderate and resolved within 1–2 days and were also more frequently noted after the second dose. No flaring of the underlying primary rheumatic disease after vaccination. No one of the study group revealed serious adverse events.ConclusionsThis is one of the early studies reporting that mRNA COVID-19 vaccine seems to be safe in children and adolescents with JIA. Almost all the reported adverse events were mild to moderate and transient. Also, no serious adverse events or flaring of the primary disease were reported.