Juvenile Idiopathic Arthritis Activity Research Articles

Anti-α-1,4-D-polygalacturonic acid antibodies as a new biomarker for juvenile idiopathic arthritis.

Diagnosing juvenile idiopathic arthritis (JIA) is challenging. Our study aimed to investigate the clinical significance of anti-α-1,4-D-polygalacturonic acid (PGA) antibodies in JIA, focusing on their role in diagnosis and assessing disease activity. In this prospective case-control study, we examined variations in serum levels of PGA-IgA and PGA-IgG among children with different types of JIA and healthy controls. Serum PGA-IgA and PGA-IgG levels were assessed concurrently in children with active and inactive JIA. This study included 126 patients diagnosed with JIA, 13 neonates, and 76 healthy children. Serum PGA-IgA and PGA-IgG levels were assessed, which revealed significant differences in PGA-IgA levels between various JIA subtypes and controls. An analysis of PGA-IgA levels in various JIA states revealed a statistically significant difference. Receiver operating characteristic (ROC) analysis demonstrated the robust predictive capability of PGA-IgA, with an AUC of 0.879 (p < 0.001), along with a specificity of 0.842 and sensitivity of 0.848. Increased levels of anti-PGA antibodies, particularly PGA-IgA, were significantly associated with JIA. PGA-IgA may serve as a sensitive biomarker for disease activity in JIA and could potentially aid in the diagnosis of JIA. Key Points • This study found a significant correlation between blood levels of PGA-IgA and juvenile idiopathic arthritis (JIA), which may provide valuable diagnostic insights. • PGA-IgA shows potential as a sensitive biomarker for the assessment of disease activity in JIA patients, helping to determine disease activity.

Diagnostic accuracy of serum calprotectin measured by CLIA and EIA in juvenile idiopathic arthritis: a proof-of-concept study.

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to assess disease activity in juvenile idiopathic arthritis (JIA). However, because these biomarkers do not always differentiate between active and inactive disease, there is a need for alternative markers such as serum calprotectin (sCal). The main aim of this proof-of-concept study was to assess the diagnostic accuracy of sCal in patients with JIA. Secondary aims were to identify the optimal sCal cut-off levels to define active disease and evaluate the association between these biomarkers and disease activity status. Serum samples were obtained from 25 pediatric patients with JIA. Serum calprotectin levels were determined by two different assays, the QUANTA FLASH chemiluminescence immunoassay (CLIA) from Inova Diagnostics and the solid-phase enzyme immunoassay (EIA) from Bühlmann Laboratories. Diagnostic accuracy was assessed for sCal CLIA, sCal EIA, CRP, and ESR. The results obtained by the CLIA and EIA methodologies were compared. We also evaluated the association between the individual each biomarkers (sCal CLIA, sCal EIA, CRP, and ESR) and disease activity (according to JADAS-27 criteria and the ACR criteria modified by Anink and colleagues). For both sCal assays (CLIA and EIA), the optimal cut-off level (ROC analysis) was the same (2.3 µg/ml). Serum calprotectin levels measured by CLIA and EIA were strongly correlated with each other (Kendall's tau-b, 0.71; p < 0.001). Compared to ESR and CRP, sCal CLIA and EIA were both more accurate (i.e., greater sensitivity) in identifying patients with active disease. By contrast, ESR and CRP were more effective in identifying patients in remission (i.e., better specificity). This proof-of-concept study shows that determination of serum calprotectin levels with CLIA or EIA can accurately identify the presence of active disease in patients with JIA.

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.

Examining the Relationship between Systemic Immune-Inflammation Index and Disease Severity in Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA), the leading childhood rheumatic condition, has a chronic course in which persistent disease activity leads to long-term consequences. In the era of biologic therapy and tailored treatment, precise disease activity assessment and aggressive intervention for high disease activity are crucial for improved outcomes. As inflammation is a fundamental aspect of JIA, evaluating it reflects disease severity. Recently, there has been growing interest in investigating cellular immune inflammation indices such as the neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammation index (SII) as measures of disease severity. The aim of this retrospective study was to explore the potential of the SII in reflecting both inflammation and disease severity in children with JIA. The study comprised 74 JIA patients and 50 healthy controls. The results reveal a notable increase in median SII values corresponding to disease severity, exhibiting strong correlations with traditional inflammatory markers, including CRP and ESR (ρ = 0.714, ρ = 0.661), as well as the JADAS10 score (ρ = 0.690). Multiple regression analysis revealed the SII to be independently associated with JADAS10. Furthermore, the SII accurately distinguished patients with high disease activity from other severity groups (AUC = 0.827, sensitivity 81.5%, specificity 66%). These findings suggest that integrating the SII as an additional measure holds potential for assessing disease activity in JIA.

Periodontal Health in Children with Juvenile idiopathic arthritis.

To investigate gingival inflammation and prevalence of four specific periodontal associated pathogens in Juvenile idiopathic arthritis (JIA) in relation to orofacial pain, jaw function and systemic inflammatory activity in JIA. Forty-five children with JIA and 16 healthy children as controls, were enrolled. Subjects were examined and classified according to the diagnostic criteria for temporomandibular disorders (DC/TMD). Pain, pain-related disability and jaw function were also assessed. A clinical periodontal examination was performed. Subgingival plaque samples were collected and analyzed for semiquantitative levels of the following periodontal pathogens; Aggregatibacter actinomycetemcomintans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. This study suggests that the periodontal disease-associated bacteria P. gingivalis and T. forsythia do not contribute to neither periodontal disease, systemic inflammatory activity nor orofacial pain and jaw dysfunction, including TMJ arthritis, in JIA patients in Sweden.

A Study on the Immunoregulatory Role of the PD1 Pathway in Juvenile Idiopathic Arthritis.

To investigate the immunoregulatory role of the Programmed-cell-Death-protein-1 (PD1) pathway, an inhibitory immune checkpoint, in Juvenile Idiopathic Arthritis (JIA). The PD1 expression on CD4+ and CD8+ T-cells was determined by flow cytometry and the PD1 soluble form (sPD1) levels by ELISA, in peripheral blood (PB)/serum and synovial fluid (SF) samples of JIA patients and healthy controls (HCs). We searched for any association in-between the biomarkers and with JIA activity. 101 Caucasian patients (69 female), aged 12 (8-15) years, and 20 HCs participated in this study. The PB PD1 expression on T-cells was higher in: a. JIA patients vs HCs (CD4: 1.24% vs 0.32%, p=0.007, CD8: 1.6% vs 0.4%, p=0.002). b. active vs inactive JIA (CD4: 1.44% vs 0.87%, p=0.072, CD8: 2.1% vs 0.93%, p=0.005). The SF PD1 expression on T-cells correlated strongly and positively with the disease activity (CD4: ρ=0.55, p=0.022, CD8: ρ=0.555, p=0.026). The SF PD1 expression on CD8 T-cells was higher in patients on-treatment vs those off-treatment (21.3% vs 5.83% p=0.004). The sPD1 levels were higher in the SF vs the serum (801pg/ml vs 367.2, p=0.013), without an association with disease activity. These results indicate an up-regulation of the PD1-pathway in JIA, at least quantitatively, especially in active disease. sPD1 is compartmentally produced at the inflamed joints. Further investigation in a larger sample of JIA patients may verify these observations and contribute to unravelling the precise role of the PD1 pathway in the pathogenesis and persistence of the joint inflammation.

Роль вітаміну D при ювенільному ідіопатичному артриті

Considering the role of vitamin D in mineral metabolism and its extracellular effects, including immunomodulation with a tendency to suppress the immune response, there is significant interest in determining its role in developing autoimmune diseases, including juvenile idiopathic arthritis (JIA). Purpose - to determine the role of vitamin D in the development and course of JIA based on a systematic analysis of literature sources over the last 7 years. A search was conducted on PubMed for articles on the role of vitamin D in the development and course of JIA, using combinations of the following terms: “vitamin D” and “juvenile idiopathic arthritis”. The review included scientific publications with available full texts published from January 2017 to August 2023. The analysis results showed significant variations in the level of 25(OH)D among patients with JIA, and the vitamin D status in the majority of JIA patients was not optimal. However, the percentage of patients with suboptimal levels and vitamin D deficiency, according to the majority of studies, was not more significant than in the general population. Nevertheless, a correlation was found between low 25(OH)D concentration and high activity of JIA. Additional vitamin D supplementation did not impact the reduction of JIA activity or the improvement of indicators of bone mineral density. However, some publications emphasize the positive effect of sun exposure in reducing the risk of JIA. Further research is needed to clarify the necessity of additional vitamin D supplementation involving a larger number of patients, standardization, selection of optimal doses, and treatment duration. No conflict of interests was declared by the authors.

Knee acoustic emissions as a noninvasive biomarker of articular health in patients with juvenile idiopathic arthritis: a clinical validation in an extended study population

BackgroundJoint acoustic emissions from knees have been evaluated as a convenient, non-invasive digital biomarker of inflammatory knee involvement in a small cohort of children with Juvenile Idiopathic Arthritis (JIA). The objective of the present study was to validate this in a larger cohort.FindingsA total of 116 subjects (86 JIA and 30 healthy controls) participated in this study. Of the 86 subjects with JIA, 43 subjects had active knee involvement at the time of study. Joint acoustic emissions were bilaterally recorded, and corresponding signal features were used to train a machine learning algorithm (XGBoost) to classify JIA and healthy knees. All active JIA knees and 80% of the controls were used as training data set, while the remaining knees were used as testing data set. Leave-one-leg-out cross-validation was used for validation on the training data set. Validation on the training and testing set of the classifier resulted in an accuracy of 81.1% and 87.7% respectively. Sensitivity / specificity for the training and testing validation was 88.6% / 72.3% and 88.1% / 83.3%, respectively. The area under the curve of the receiver operating characteristic curve was 0.81 for the developed classifier. The distributions of the joint scores of the active and inactive knees were significantly different.ConclusionJoint acoustic emissions can serve as an inexpensive and easy-to-use digital biomarker to distinguish JIA from healthy controls. Utilizing serial joint acoustic emission recordings can potentially help monitor disease activity in JIA affected joints to enable timely changes in therapy.

Juvenile idiopathic arthritis in the young adult. Methodology, objectives, and initial data from the JUVENSER registry

ObjectivesTo describe the methodology, objectives, and initial data of the registry of young adult patients diagnosed with Juvenile Idiopathic Arthritis (JIA), JUVENSER. The main objective of the project is to know the sociodemographic and clinical characteristics, and disease activity of patients with JIA reaching the transition to adulthood. Material and methodLongitudinal, prospective, multicentre study, including patients between 16 and 25 years old, with a diagnosis of JIA in any of its categories. The main objective is to determine the characteristics and activity of JIA in the young adult. It includes sociodemographic variables, clinical variables, disease activity and joint damage rates, data on the use of health resources, and treatments used. The total duration of the project will be 3 years. A cohort of 534 young adult patients was obtained. ConclusionsThe JUVENSER registry will constitute a cohort of young adults with JIA, which will allow the evaluation of the clinical characteristics and response to treatment of patients with disease onset in childhood, moving to adult clinics.

The effect of etanercept therapy on adrenal steroid metabolism in juvenile idiopathic arthritis: a steroid metabolomics approach

ObjectiveTo evaluate the impact of anti-tumor necrosis factor-alpha (TNFα: etanercept [Etanercept ®]) therapy on adrenal activity in juvenile idiopathic arthritis (JIA) .MethodEleven JIA patients aged 12 ± 6.2 years with a disease duration of 6.3 ± 5.2 years were enrolled. They were treated once weekly with etanercept (0.8 mg/kg) for 3 ± 2.8 years. Urine samples for gas chromatography-mass spectrometry steroid hormone analysis were collected before, and 1 and 3 days after etanercept injection and compared to age- and sex-matched healthy controls.ResultsThe levels of 21 of the 31 metabolites were low before etanercept treatment. Those 21 metabolites included 4 C19 steroids (androgens), 5 C C21 steroid hormone intermediates, 10 cortisol metabolites, and 2 corticosterone metabolites. One day after treatment, only 5 of the 21 metabolite levels remained low. They included 2 C19 metabolites, 2 C21 steroid metabolites and 1 cortisol metabolite β –Cortol (β-Cl). Three days after treatment, the only metabolites levels that continued to be low were 2 C19 metabolite, 2 C21 steroid hormone intermediates and 1 cortisol metabolite α-Cortol (a-Cl), while the remaining 15 metabolites had already normalized after 1 day. Dehydroepiandrosterone-sulfate and 17-hydroxypregnenolone metabolite levels were the last ones to recover. Urinary metabolite ratios reflecting cytochrome P450 CYP21A2 (21-hydroxylase) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzymatic activitieswere lower in JIA patients than in controls, although significant was not reached.ConclusionAlmost all of the pre-etanercept treatment cortisol urinary metabolite levels were significantly lower than normal, and almost all rose to normal values by 1 day after treatment. The therapeutic effect of anti-TNFα treatment in JIA may be related to its effect on the restoration of adrenal function and cortisol levels.

Musculoskeletal Ultrasound and the Assessment of Disease Activity in Juvenile Idiopathic Arthritis.

To determine the frequency of subclinical synovitis on musculoskeletal ultrasonography (MSUS) in juvenile idiopathic arthritis (JIA) and correlate patient- and provider-reported outcome measures with MSUS synovitis. JIA patients with an active joint count (AJC) of >4 underwent a 42-joint MSUS performed at baseline and 3 months. B-mode and power Doppler images were obtained and scored (range 0-3) for each of the 42 joints. Outcomes evaluated included physician global assessment of disease activity (PhGA), patient global assessment of disease activity (PtGA), patient pain, Childhood Health Assessment Questionnaire (C-HAQ), and AJC. Subclinical synovitis was defined as synovitis detected by MSUS only. Generalized estimation equations were used to test the relationship between clinical arthritis (positive/negative) and subclinical synovitis (positive/negative). Spearman's correlation coefficients (rs ) were calculated to determine the association between MSUS synovitis and patient- and physician-reported outcomes. In 30 patients, subclinical synovitis was detected in 30% of joints. Clinical arthritis of the fingers, wrists, and knee joints was significantly associated with MSUS synovitis in these joints. PtGA and the C-HAQ had a moderate (rs =0.44, P= 0.014) to weak (rs =0.37, P=0.045) correlation with MSUS synovitis. There was a statistically significant strong correlation between MSUS synovitis and PhGA (rs =0.61, P=0.001), but a weak correlation with AJC (rs =0.37, P=0.048) at the follow-up visit. Subclinical synovitis was commonly observed in this cohort of JIA patients. The fair-to-moderate correlation of MSUS synovitis with patient- and provider-reported outcomes suggests that MSUS assesses a different, possibly more objective, domain not determined by traditional JIA outcome measurements.

Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis

To study the expression levels of CD4+NKG2D+ T cells and NKG2D soluble ligands, the soluble MHC class I chain-related molecules A and B (sMICA/sMICB) in the active stage and stable stage of juvenile idiopathic arthritis (JIA) and their role in the disease activity of JIA. Nineteen children with systemic JIA and 20 children with articular JIA who were diagnosed in Children's Hospital of Chongqing Medical University from November 2019 to December 2021 were enrolled in this prospective study. Six healthy children were enrolled as the control group. After peripheral blood samples were collected, ELISA was used to measure the levels of sMICA and sMICB, and flow cytometry was used to measure the percentage of CD4+NKG2D+ T cells. Systemic Juvenile Arthritis Disease Activity Score-27 (sJADAS-27)/Juvenile Arthritis Disease Activity Score-27 (JADAS-27) was used to evaluate the disease activity in children with JIA. The Pearson correlation analysis and the receiver operating characteristic (ROC) curve were used to assess the role of CD4+NKG2D+ T cells, sMICA and sMICB in the disease activity of JIA. The active systemic JIA and active articular JIA groups had a significant increase in the percentage of CD4+NKG2D+ T cells compared with the control group and their corresponding inactive JIA group (P<0.05). The JIA groups had significantly higher levels of sMICA and sMICB than the control group (P<0.05), and the active articular JIA group had a significantly higher level of sMICB than the stable articular JIA group (P<0.05). In the children with JIA, the percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB were positively correlated with sJADAS-27/JADAS-27 disease activity scores (P<0.05). The ROC curve analysis showed that sMICB had an area under the curve of 0.755 in evaluating the disease activity of JIA, with a specificity of 0.90 and a sensitivity of 0.64. The percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB increase in children with JIA compared with healthy children and are positively correlated with the disease activity of JIA, suggesting that CD4+NKG2D+ T cells and NKG2D ligands can be used as potential biomarkers for evaluating the disease activity of JIA.

Calcium homeostasis and certain aspects of its disturbances in juvenile idiopathic arthritis

Background. In the pathogenesis of juvenile idiopathic arthritis (JIA), the main role is played by immunopathological changes in the body with a loss of tolerance to the elements of own tissues; herewith, disorders of calcium and bone metabolism are very important. Such changes occur as a result of autoimmune inflammation, pharmacotherapy, and the influence of a number of other factors that negatively affect calcium homeostasis in the body. Purpose: to study the features of calcium homeostasis and certain aspects of its disorders with an assessment of the structural and functional state of bone tissue, taking into account clinical subtypes and disease activity. Material and methods. Sixty-two children with JIA aged 3.5 to 16 years were examined, of them 11 had systemic and 51 had oligo- and polyarthritis. There were determined serum concentrations of a total calcium using the Lachema test kit (Czech Republic), protein-bound and ultrafiltered fractions, content of inorganic phosphorus (with the generally accepted spectrophotometric method using the Cobas 6000 analyzer and test systems by Roche Diagnostics, Switzerland), the activity of total alkaline phosphatase and its isoenzymes (bone and intestinal) using the Lachema test system (Czech Republic). Ultrasonic osteometry of the calcaneal (trabecular) bone was performed on the Achilles device (Lunar, USA). Results. A significant decrease was found in the average concentration of total calcium, protein-bound calcium in systemic JIA and in high disease activity. The concentration of the ultrafiltered calcium fraction decreased only with high disease activity. The average concentration of inorganic phosphorus in children with oligo- and polyarthritis was within the normal range, while in systemic JIA it decreased. A significant decrease in the serum content of inorganic phosphorus, as well as in the activity of total alkaline phosphatase and its bone isoenzyme was detected in patients with high activity of systemic JIA. In patients with JIA (oligo-, polyarthritis) characterized by a slowly progressive rheumatic process, only the indicator of broadband ultrasound attenuation significantly changed during the first year of the disease, while the speed of ultrasound propagation and the index of bone tissue strength were not changed. In patients with a longer duration of the disease, all densitometric indicators decreased significantly. In the group of patients with systemic JIA and a rapidly progressive course, high activity of the disease that required a glucocorticoid therapy, a significant loss of bone mass was noted by the end of the first year of the disease. Conclusions. In JIA, there are changes in the concentration of total calcium and its protein-bound and ultrafiltered fractions in the blood serum, which indicate the tension of calcium-phosphorus metabolism and possible calcium deficiency in the body already at the early stages of the pathological process. A decrease in the activity of the alkaline phosphatase and its bone isoenzyme is associated with a violation of the structural and functional changes in the bone system of patients with JIA, which progresses with the duration of the disease. Patients with JIA require timely diagnosis and monitoring of calcium-phosphorus metabolism disorders with an assessment of the structural and functional state of the bone system for purposeful correction of comprehensive therapy due to the use of drugs in order to increase bone tissue regeneration, reduce the progression of osteopenia and osteoporosis, and preserve the health of the growing organism.

ВЛИЯНИЕ АКТИВНОСТИ ВОСПАЛИТЕЛЬНОГО ПРОЦЕССА ПРИ ЮВЕНИЛЬНОМ ИДИОПАТИЧЕСКОМ АРТРИТЕ НА СОСТОЯ-НИЕ ЭРИТРОПОЭЗА. ЗНАЧЕНИЕ РЕТИКУЛОЦИТАРНЫХ ИНДЕК-СОВ

The article deals with the influence of the activity of juvenile idiopathic arthri-tis (JIA) on the state of the reticulocyte link of erythropoiesis. The aim of the study was to study the effect of the activity of the inflammatory process in JIA on erythropoiesis by studying reticulocyte parameters. Research methods: 118 patients with JIA and 30 patients of the comparison group were included in the study. Patients underwent a complete blood count with the determination of the following parameters: the absolute and relative reticulocyte count (Ret# and Ret‰), the amount of hemoglobin in the reticulocyte (Ret-He) and erythrocyte (RBC-He), the fraction of immature reticulocytes (IRF), the distribution of reticu-locytes by degrees of light scattering into high fluorescent (immature, HFR), me-dium fluorescent (immature, MFR) and low fluorescent (mature, LFR). Results. Statistically significant differences were found in the content of reticulocytes and in the qualitative ratio of reticulocytes, the content of hemoglobin in the reticulo-cyte and erythrocyte, delta-hemoglobin, depending on the activity of the inflam-matory process. Findings. The activity of the inflammatory process affects eryth-ropoiesis in the form of an increase in the production of reticulocytes, predomi-nantly immature forms with a peak at a high degree of activity. As the activity of the inflammatory process increases, the need for iron increases in order to main-tain adequate hemoglobin synthesis. As disease activity increases, the risk of mi-crocytic anemia increases.

Neutrophil Count, Platelet Indices, CRP and Their Association with Disease Activity of Juvenile Idiopathic Arthritis (JIA): A Study from Bangladesh

Background: Chronic inflammation of the joints in JIA patients is associated with raised levels of serum inflammatory biomarkers, which vary according to disease activity. Neutrophil count, platelet count, mean platelet volume (MPV), platelet distribution width (PDW), ESR and CRP are the essential markers to evaluate the disease activity status of JIA patients. Objectives: To assess neutrophil count, platelet count, MPV, PDW, CRP and Juvenile Arthritis Disease Activity Score (JADAS) in JIA patients and determine their association at the initial visit and six months after treatment. Methods: This prospective observational study was conducted from March 2019 to December 2020 in the department of paediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Fifty newly diagnosed JIA cases fulfilling the ILAR classification criteria were included in the study. Disease activity was assessed by JADAS 27. JADAS 27 and inflammatory biomarkers were measured at the initial visit and six months of treatment and these were compared. Results: Mean neutrophil count, platelet count, and CRP significantly decreased at follow-up after six months of treatment. MPV and PDW were increased after six months compared to the initial visit, and the change was significant. Mean JADAS 27 also decreased significantly at follow-up. Neutrophil count, Platelet indices and CRP had a significant association with JADAS 27. Conclusion: In this study, neutrophil count, platelet indices, and CRP after six months of treatment were improved. A significant association of JADAS 27 was found with platelet indices, neutrophil count and CRP.

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.

Juvenile idiopathic arthritis of the knee: is contrast needed to score disease activity when using an augmented MRI protocol comprising PD-weighted sequences?

ObjectiveTo compare unenhanced versus enhanced knee joint magnetic resonance imaging (MRI) to assess disease activity of juvenile idiopathic arthritis (JIA).MethodsFifty-three knee joint MRI examinations were performed on a 3-Tesla system in 27 patients (age: 11.40 ± 3.61 years; 21 females, 6 males). MRI protocols comprised PD-weighted sequences in addition to the widely used standard protocol. JIA subgroups comprised oligoarticular arthritis (n = 16), extended oligoarthritis (n = 6), rheumatoid factor-negative polyarticular arthritis (n = 3), enthesitis-related arthritis (n = 1), and psoriatic arthritis (n = 1). MR images were retrospectively analyzed by 3 experienced radiologists in two readings, using JAMRIS (juvenile arthritis MRI scoring) system and a modified IPSG (international prophylaxis study group) classification. In the first reading session, only unenhanced MR images were evaluated. In a second reading session, all images before and after contrast medium application were included. In order to avoid bias, an interval of at least 2 weeks was set between the two readings. The clinical JADAS10 (juvenile arthritis disease activity score) was calculated including clinical assessment and laboratory workup and correlated with MRI scores. Statistical analysis comprised Pearson’s correlation for correlating two scoring results of unenhanced and the enhanced MRI, intra-class correlation coefficient (ICC) for inter- and intra-reader agreement. Diagnostic accuracy was calculated using ROC (receiver operating characteristics) curve analysis.ResultsInter-reader agreement determined by ICC for unenhanced and enhanced MRI scores for IPSG was moderate (0.65, 95% CI 0.51–0.76, and 0.62, 95% CI 0.48–0.75) and high for JAMRIS (0.83, 95% CI 0.75–0.89, and 0.82, 95% CI 0.74–0.89). Intra-reader agreement was good to very good for JAMRIS (0.85 95% CI 0.81–0.88, 0.87 95% CI 0.83–0.89 and 0.96 95% CI 0.92–0.98) and IPSG (0.76 95% CI 0.62–0.86, 0.86 95% CI 0.77–0.92 and 0.92 95% CI 0.86–0.96). Scores of unenhanced MRI correlated with contrast-enhanced MRI: JAMRIS (r = 0.97, R2 = 0.93, p < 0.01), modified IPSG (r = 0.95, R2 = 0.91, p < 0.01). When using JADAS10 as a reference standard, moderate accuracy for both unenhanced and enhanced MRI scores was noted: JAMRIS (AUC = 0.68, 95% CI 0.51–0.85, and AUC = 0.66, 95% 0.49–0.82), IPSG score (AUC = 0.68, 95% 0.50–0.86, and AUC = 0.61, 95% 0.41–0.81).ConclusionsOur results suggest that contrast agent application could be omitted in JIA patients with an augmented knee MRI protocol comprising PD-weighted sequence.Key Points• Unenhanced MRI can detect disease activity of the knee joint in patients with JIA with equally high accuracy compared to contrast-enhanced MRI.• The intra- and inter-reader agreement was high for unenhanced and enhanced MRI JAMRIS scores, which indicate relatively good applicability of the scoring system, even for less experienced readers.• When using the clinical JADAS10 as a reference standard for the detection of disease activity, moderate accuracy for both unenhanced and enhanced MRI scores, both JAMRIS and IPSG, was noted, which might be caused by the fact that the majority of patients had either no or minimal clinical disease activity.

Obesity as a comorbidity in children and adolescents with autoimmune rheumatic diseases.

Childhood obesity is the public health issue with alarming rates recorded throughout developed world and an important modifiable health risk for developing various chronic diseases, with childhood-onset autoimmune rheumatic diseases among them also. The aim of this article was to summarize epidemiological, pathophysiological and clinical implication of obesity on juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), juvenile dermatomyositis (JDM), IgA vasculitis (IgAV) and Kawasaki disease (KD). We reviewed PubMed database and selected 74 relevant articles. Epidemiological data of obesity among children with autoimmune rheumatic diseases indicate an increased prevalence of it. Pathophysiological link between obesity, humoral adipokines and cytokines released from fat tissue and childhood-onset autoimmune rheumatic diseases is complex and still not entirely clear. From the clinical point of view, obesity was not associated with disease activity in JIA and cSLE, but proved to contribute on functional impairment in both diseases and affect poor treatment response in JIA patients. Early atherosclerosis and cardiovascular disease (CVD) development in obese children and adolescents with JIA, cSLE and JDM are certainly important obesity-related complications. Understanding how obesity affects children and adolescents with autoimmune rheumatic diseases may encourage clinicians to consider taking better preventive strategies in this population to improve their long-term outcome.

CURRENT ISSUES OF VITAMIN D IN JUVENILE IDIOPATHIC ARTHRITIS

Background. Children with juvenile idiopathic arthritis (JIA) represent a special cohort of patients with chronic somatic pathology, characterized by severe damage to the musculoskeletal system and other vital organs and systems, which is associated with immune and metabolic changes in the body. Data regarding the provision of vitamin D (VD) in patients with JIA and the significance of its deficiency in the initiation, activation of the autoimmune process, the prognosis of the course of the disease, the risk of developing complications and the effectiveness of protocol therapy are contradictory. Objective. To investigate the body's supply of vitamin D in patients with juvenile idiopathic arthritis with the determination of the trigger factors of its deficiency, the assessment of the immune status and changes in the nucleotide sequence in the genes of innate immunity. Materials and methods. Research was conducted during 2016-2021 at the Institute in 119 patients with JIA aged 6 to 12 years. The concentration of 25OHD was determined in blood serum using commercial Vitamin D3 kits (Screeningkit, Switzerland). Immunological studies were performed by flow cytofluorimetry and enzyme immunoassay. For panel sequencing of 407 genes regulating immune functions, high-throughput panel exome sequencing was used on Illumina's HiSeq machine (made in the USA) at the Invitae laboratory (USA). The obtained digital data were processed by methods of statistical analysis using the Microsoft Excel computer package. Results. A high frequency of low supply of vitamin D in patients with JIA was revealed: vitamin D insufficiency was diagnosed in 96 (80.6 %), and its deficiency - in 38 (31.9 %) children. The lowest levels of 25ОНD concentration in blood serum (less than 15 ng/ml) are observed in patients with stage II–III disease activity, especially at the beginning of the pathological process. Vitamin D deficiency (DVD) was associated with the activity and severity of the clinical course, frequent exacerbation of the joint syndrome, the expressiveness of changes in the humoral and cellular immunity of patients. The main risk factors for reducing the body's supply of WD in patients with JIA have been determined, which must be taken into account during their observation and treatment. High activity of JIA in patients with VD deficiency in the body was associated with a significant increase in the number of CD3+ T-cells, CD3+CD4+ helper-inducer T-cells, activated HLA-DR+/CD3+ T-cells, ESR, C-reactive protein concentration (CRP), tumor necrosis factor (TNF), circulating immune complexes (CIC), immunoglobulins, which allows considering DWD as a likely predictor of severe and prognostically unfavorable course of rheumatic disease. Nucleotide sequence changes in the NOD2 gene were detected in 18.1 % of patients with JIA: c.2104C&gt;T (p.Arg702Trp), c.3019dupC (p.Leu1007Profs*2). The of variable changes in patients with JIA is statistically significantly different from the population [VSh = 11.39; 95 % CI (2.39-54.22)]. DVD was detected in all children with mutations in the NOD2 gene – (17.2 ± 3.29) ng/ml, and in children without changes in the nucleotide sequence - in 23 (85.1 %) children [SS = 0.097; DI (0.03-0.31)], the concentration of VD is significantly higher - [(26.68 ± 2.34) ng/ml, p = 0.026]. Conclusions. The conducted studies confirm the presence of a decrease in the body's supply of vitamin D in patients with JIA, which is associated with a high activity of the pathological process and pronounced immunological changes in the body, which allows us to consider its deficiency as a likely predictor of a severe and prognostically unfavorable course of the disease. It has been proven that the concentration of vitamin D in JIA is higher in patients without changes in the nucleotide sequence in the NOD2 gene, which must be taken into account when predicting and evaluating the body's response to the treatment of juvenile arthritis. Key words: juvenile idiopathic arthritis, vitamin D, immunological status, genetic sequencing, children.

The role of S100A12 and Toll-like receptor 4 in assessment of disease activity in familial Mediterranean fever and juvenile idiopathic arthritis.

Our aim was to investigate the possible relationship between the serum S100A12 and Toll-like receptor 4 (TLR4) levels, and the activity of familial Mediterranean fever (FMF) and juvenile idiopathic arthritis (JIA) in accordance with the routine biochemical parameters. Furthermore, the effectiveness of these 2 biomarkers in distinguishing FMF from JIA has been evaluated. Sixty-nine children with FMF, 68 children with JIA, and 35 healthy children were included in this study. S100A12 and TLR4 levels were measured by the sandwich enzyme-linked immunosorbent assay technique. In the FMF patient group, serum S100A12 level was found to be significantly higher than in both the JIA and control groups (P=.000 and P=.000, respectively). Although S100A12 levels were higher in the attack period compared to the attack-free period, this increase was not statistically significant (P > .05). TLR4 levels were statistically significantly higher in the attack period compared to the attack-free period in children with FMF (P < .05). Although there was no relationship between S100A12 levels and disease activity, there is a clear correlation between S100A12 and the Auto-Inflammatory Disease Activity Index in attack-free FMF patients (r=0.612 P=.000). Serum S100A12 levels were not found to be a potentially valuable biomarker for assessing disease activity in either FMF or JIA. However, TLR4 levels were found to be a valuable biomarker for assessing disease activity in children with FMF. Further research which includes serial monitoring of S100A12 and TLR4 levels in a large cohort will provide detailed information about accuracy of these 2 potential biomarkers in both patients group.