Child ; Humans ; Arthritis, Juvenile/drug therapy* ; Macrophage Activation Syndrome/etiology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Humans ; Arthritis, Juvenile/genetics* ; Intracellular Signaling Peptides and Proteins/genetics* ; Genetic Predisposition to Disease

Humans ; Arthritis, Juvenile

Humans ; Arthritis, Juvenile/drug therapy* ; China

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS 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.
Child ; Humans ; Arthritis, Juvenile/pathology* ; Ligands ; NK Cell Lectin-Like Receptor Subfamily K ; Prospective Studies ; T-Lymphocytes/pathology*

OBJECTIVES: To study the expression of V-domain Ig suppressor of T cell activation (VISTA) in peripheral blood of children with juvenile idiopathic arthritis (JIA) and its role in the pathogenesis of JIA. METHODS: In this prospective study, peripheral blood was collected from 47 children with different subtypes of JIA and 10 healthy children. Flow cytometry was used to measure the expression levels of VISTA, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on CD14⁺ mononuclear cells, CD4⁺ T lymphocytes, and CD8⁺ T lymphocytes. RESULTS: The children with JIA had a significantly lower expression level of VISTA than the healthy children (P<0.05). There was a significant difference in the expression of VISTA between the children with different subtypes of JIA, with the lowest expression level in those with systemic JIA (P<0.05). There was also a significant difference in the expression of VISTA between different immune cells, with a significantly higher expression level on the surface of monocytes (P<0.05). Correlation analysis showed that VISTA was negatively correlated with the expression of IFN-γ and TNF-α on CD4⁺ T cells (r=-0.436 and -0.382 respectively, P<0.05), CD8⁺ T cells (r=-0.348 and -0.487 respectively, P<0.05), and CD14⁺ mononuclear cells (r=-0.582 and -0.603 respectively, P<0.05). CONCLUSIONS The insufficient expression of VISTA may be associated with the pathogenesis of JIA, and enhancing the immunomodulatory effect of VISTA might be one option for the treatment of JIA in the future.
Child ; Humans ; Arthritis, Juvenile/pathology* ; Tumor Necrosis Factor-alpha/metabolism* ; CD8-Positive T-Lymphocytes ; Prospective Studies ; Interferon-gamma/metabolism*

OBJECTIVE: To analyze and compare the clinical and laboratory characteristics of macrophage activation syndrome (MAS) in patients with systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD), and to evaluate the applicability of the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organization classification criteria for MAS complicating systemic juvenile idiopathic arthritis (sJIA) in different auto-immune diseases contexts and to propose new diagnostic predictive indicators. METHODS: A retrospective analysis was conducted on the clinical and laboratory data of 24 SLE patients with MAS (SLE-MAS) and 24 AOSD patients with MAS (AOSD-MAS) who were hospitalized at Peking University People's Hospital between 2000 and 2018. Age- and sex-matched SLE (50 patients) and AOSD (50 patients) diagnosed in the same period without MAS episodes were selected as controls. The cutoff values for laboratory indicators predicting SLE-MAS and AOSD-MAS were determined using receiver operating characteristic (ROC) curves. Furthermore, the laboratory diagnostic predictive values for AOSD-MAS were used to improve the classification criteria for systemic juvenile idiopathic arthritis-associated MAS (sJIA-MAS), and the applicability of the revised criteria for AOSD-MAS was explored. RESULTS: Approximately 60% of SLE-MAS and 40% of AOSD-MAS occurred within three months after the diagnosis of the underlying diseases. The most frequent clinical feature was fever. In addition to the indicators mentioned in the diagnosis criteria for hemophagocytic syndrome revised by the International Society for Stem Cell Research, the MAS patients also exhibited significantly elevated levels of aspartate aminotransferase and lactate dehydrogenase, along with a significant decrease in albumin. Hemophagocytosis was observed in only about half of the MAS patients. ROC curve analysis demonstrated that the optimal discriminative values for diagnosing MAS was achieved when SLE patients had ferritin level≥1 010 μg/L and lactate dehydroge-nase levels≥359 U/L, while AOSD patients had fibrinogen levels≤225.5 mg/dL and triglyceride levels≥2.0 mmol/L. Applying the 2016 sJIA-MAS classification criteria to AOSD-MAS yielded a diagnostic sensitivity of 100% and specificity of 62%. By replacing the less specific markers ferritin and fibrinogen in the 2016 sJIA-MAS classification criteria with new cutoff values, the revised criteria for classifying AOSD-MAS had a notable increased specificity of 86%. CONCLUSION Secondary MAS commonly occurs in the early stages following the diagnosis of SLE and AOSD. There are notable variations in laboratory indicators among different underlying diseases, which may lead to misdiagnosis or missed diagnosis when using uniform classification criteria for MAS. The 2016 sJIA-MAS classification criteria exhibit high sensitivity but low specificity in diagnosing AOSD-MAS. Modification of the criteria can enhance its specificity.
Adult ; Humans ; Child ; Macrophage Activation Syndrome/complications* ; Arthritis, Juvenile/diagnosis* ; Still's Disease, Adult-Onset/diagnosis* ; Retrospective Studies ; Lupus Erythematosus, Systemic/diagnosis* ; Fibrinogen ; Ferritins

Objective: To evaluate the efficacy and safety of intra-articular injection of adalimumab (ADA) in the treatment of refractory oligoarticular juvenile idiopathic arthritis (JIA). Methods: This was a retrospective study. Clinical data on age, gender, and symptoms of joint swelling and pain were collected from 11 children with refractory oligoarticular JIA involving only knee joints admitted to Department of Rheumatism and Immunology of Children's Hospital, Capital Institute of Pediatrics from November 2019 to October 2020. The physician and parent-child evaluation of disease activity, the number of active joints, and the level of erythrocyte sedimentation rate (ESR) at different treatment time points were analyzed at every 4-week observation point after drug administration, and the non-parametric Kruskal-Wallis test was used to compare the differences in clinical evaluation indicators and changes in laboratory tests at different treatment times. The follow-up period was 6 months. Results: Among the 11 children, 5 were boys and 6 were girls. The age was 3.0 (2.8) years. All 11 children had symptoms of joint swelling and pain as well as limitation of movement. After 3 intra-articular injections of ADA, the joint symptoms of 11 children were better than before treatment; the joint symptoms of 7 children disappeared completely, and no recurrence occurred during the 6-month follow-up period. At different treatment times, physician and parent-child evaluation of disease activity, a gradual decrease in the number of active joints in the children, ESR, and juvenile arthritis disease activity score with 27 joints were all statistically significant (χ²=53.99, 59.37, 32.87, 40.07, 54.00, all P<0.001).No significant adverse drug reactions were observed in any of the 11 children during treatment and follow-up. Conclusion: Intra-articular injection of ADA in the treatment of refractory oligoarticular JIA has a significant effect in controlling joint symptoms and is relatively safe.
Adalimumab/therapeutic use* ; Arthritis, Juvenile/drug therapy* ; Child ; Child, Preschool ; Female ; Glucocorticoids/therapeutic use* ; Humans ; Injections, Intra-Articular ; Male ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the clinical characteristics of systemic juvenile idiopathic arthritis combined with coronary artery dilatation. Methods: A retrospective analysis was performed on the clinical data, including clinical manifestations, blood routine, inflammatory factors, echocardiography, vascular ultrasound and CT angiography, treatment and outcomes, etc, of 5 cases with systemic juvenile idiopathic arthritis combined with coronary artery dilation admitted to Department of Rheumatology in the affiliated Children's Hospital of Capital Institute of Pediatrics from May 2019 to June 2021. Results: There were 2 males and 3 females among 5 cases. The onset age ranged from 7 months to 4 years 7 months.The diagnostic time ranged from 1.5 months to 3.0 months.Four cases were diagnosed as atypical Kawasaki disease. Three cases showed unilateral coronary artery dilation.Two cases showed bilateral coronary artery dilation.Four cases developed multiple organ injuries.Three cases developed macrophage activation syndrome.Three cases developed lung injury.Two cases developed pericardial effusion.One case developed pulmonary hypertension.As for treatment, 3 cases treated with methylprednisolone pulse therapy and methotrexate combined with cyclosporine, improved after the final application of biological agents, and have stopped prednisone. The other 2 cases were treated with adequate oral prednisone and gradually reduced, and methotrexate was added at the same time, 1 case relapsed in the process of reduction. No other vascular involvement was found in 5 cases. Coronary artery dilation recovered completely after 1 to 3 months of treatment. Conclusions: Systemic juvenile idiopathic arthritis combined with coronary artery dilatation has the clinical characteristics of small onset age, long diagnostic time, prone to multiple organ injuries. Corticosteroids and conventional immunosuppressive agents are not sensitive, and biological agents should be used as soon as possible.The prognosis of coronary artery dilation is good after timely treatment.
Arthritis, Juvenile/drug therapy* ; Biological Factors/therapeutic use* ; Child ; Coronary Aneurysm/etiology* ; Coronary Artery Disease/therapy* ; Dilatation ; Dilatation, Pathologic ; Female ; Humans ; Infant ; Male ; Methotrexate ; Prednisone/therapeutic use* ; Retrospective Studies

Arthritis, Juvenile/complications* ; Humans ; Rheumatoid Nodule