A preliminary study on the role of V-domain Ig suppressor of T cell activation in juvenile idiopathic arthritis / 中国当代儿科杂志

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.

Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis / 中国当代儿科杂志

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.

Temporomandibular joint disorders as the only manifestation of juvenile idiopathic arthritis: a case report / Comprometimento da articulação temporomandibular como única manifestação da artrite idiopática juvenil: um relato de caso

ABSTRACT Juvenile idiopathic arthritis is a term used to include all chronic childhood arthritis of unknown etiology. It is characterized by chronic inflammation persisting for at least 6 weeks, beginning before 16 years of age. The characteristics present are chronic synovitis, arthralgia, impaired joint mobility in at least one joint, and erosion with destruction of cartilage and subchondral bone, that could be associated or not with systemic involvement, according to each subtype of the disease. During the pathologic process, the temporomandibular joint can be involved by the juvenile idiopathic arthritis, resulting in severe mandibular dysfunction, with higher frequency in female patients. Initially, these lesions can show minor alterations like flattening of the condyle, erosions, and evolve to severe lesions, like destruction of the head of the condyle. We report a case of male patient who had destruction of both condyles, as a result from juvenile idiopathic arthritis. Proposed mechanisms to explain the juvenile idiopathic arthritis was reviewed. In this report the patient did not have pain or inflammatory process, and the temporomandibular diseases was the only manifestation.

RESUMO Artrite idiopática juvenil é um termo usado para incluir toda artrite infantil crônica de etiologia desconhecida. É caracterizada por uma inflamação crônica, que persiste por pelo menos 6 semanas, com início antes dos 16 anos de idade. As características presentes são sinovite crônica, artralgia, mobilidade articular diminuída em pelo menos uma articulação, e erosão com destruição da cartilagem e do osso subcondral, podendo ser associada ou não com o envolvimento sistêmico, de acordo com cada subtipo da doença. Durante o processo patológico, a articulação temporomandibular pode ser envolvida pela artrite idiopática juvenil, resultando em disfunção mandibular severa, com maior frequência em pacientes do sexo feminino. Inicialmente, estas lesões podem mostrar pequenas alterações, como achatamento do côndilo e erosões, e evoluir para lesões graves, como a destruição da cabeça do côndilo. Relatou-se o caso de um paciente do sexo masculino, que apresentou destruição de ambos os côndilos, como resultado da artrite idiopática juvenil. Os mecanismos para explicar a artrite idiopática juvenil foram revisados na literatura. Neste relato de caso, o paciente não apresentou dor e nem processo inflamatório, sendo o comprometimento da articulação temporomandibular a única manifestação.

A Artrite Idiopática Juvenil como fator de risco para a erosão dentária: estudo preliminar / The Juvenile Idiopathic Arthritis as a risk factor for dental erosion: a preliminary study

O objetivo deste estudo foi avaliar se a presença da artrite idiopática juvenil (AIJ) em crianças e adolescentes pode ser considerada como indicador de risco para a erosão dentária. Para tal, foram utilizadas oitenta crianças e adolescentes com diferentes tipos de AIJ e 23 pacientes saudáveis como controle. Os critérios de inclusão foram diagnóstico de AIJ e classificação do subtipo de acordo com os critérios da Liga Internacional das Associações de Reumatologia(ILAR). Os dados sobre variáveis nutricionais, fatores socioeconômicos, vômitos, ingestão de medicamentos, hábitos alimentares e orais foram coletados por meio de questionário estruturado.Todos os pacientes foram submetidos a medição do fluxo salivar e exame clínico usando o índice Exame Básico de Desgaste Erosivo (BEWE). Dezesseis pacientes, todos afetados pelo subtipo oligo articular de AIJ mostraram redução da quantidade de saliva estimulada; dois deles apresentaram erosão e relataram consumo diário de refrigerantes. Foi relatado vômitos (uma vez por dia) por nove pacientes devido à ingestão de metotrexato sem correlação com o subtipo de AIJ. Nenhum deles exibiu erosão. O indicador de risco para a erosão dentária foi o subtipo de AIJ (artrite oligo articular), não havendo correlação significativa da presença de erosão dentária com as variáveis nutricionais, ingestão de medicamentos, hábitos alimentares e orais.

The purpose of this study was evaluate the existence of prevalence and risk indicators of dental erosion in patients affected by juvenile idiopathic arthritis (JIA). Eighty patients (61 females and 19males) with different kinds of JIA and 23 healthy control ones aging from 3 to 19 years were included in the study. The inclusion criteria were diagnosis of JIA and subtype classification according to the International League of Associations for Rheumatology (ILAR) criteria. Data on nutrition al variables, socioeconomic factors, vomiting, drug intake and dietary and oral habits were collected using a questionnaire. All patients underwent saliva measurement and clinical examination using Basic Erosive Wear Examination (BEWE) Index. Sixteen patients, all affected by the oligo articular subtype of JIA showed a reduced quantity of stimulated saliva; two of them showed erosion andre ported a daily soft drink intake. Vomiting (once a day) was reported by nine patients and was dueto methotrexate intake with no correlation with JIR subtype. None of them exhibited erosion. Risk indicator for wear was JIA subtype (oligo articular arthritis). There was no significant correlation of the presence of dental erosion with nutritional variables, drug intake or dietary and oral habits.

Induction of metalloproteinases expression by TLR ligands in human fibroblast like synoviocytes from juvenile idiopathic arthritis patients.

Background & objective: Juvenile idiopathic arthritis (JIA) is characterized by chronic synovitis, cartilage damage and bone erosion. Both genetic and environmental factors and microbes probably play a role in pathogenesis. Microbes are recognized by Toll like receptors (TLRs) and activate innate immune response. We studied the ability of bacterial and viral products to produce matrix metalloproteinases (MMPs) and cytokines by fibroblast like synoviocytes (FLS) from patients with JIA. Methods: FLS were cultured from synovial fluid (SF) of patients with JIA and subsequently stimulated for 48 h by different TLR ligands [peptidoglycan (PG) for TLR2, poly(I-C) for TLR3, lipopolysaccharide (LPS) for TLR4, flagellin for TLR5, imiquimod for TLR7 and CpG DNA for TLR9]. Later the production of IL6, IL8, MMP-1, MMP-3, tissue inhibitors of metalloproteinase (TIMP1) was measured in the culture supernatants by ELISA. Expression of TLR2, TLR4, TLR7 and TLR9 was studied in FLS derived from JIA patients by RT-PCR. Results: IL6, IL8, MMP3 and MMP1 production was induced on stimulation of FLS with TLR2 ligand, TLR3 ligand, TLR4 ligand, TLR5 ligand but not with TLR7 ligand and TLR9 ligand. There was no effect of these ligands on the production of TIMP thus the balance was tilted in favour of MMPs after TLR ligation. TLR2, TLR4 and low expression of TLR9 was found but, no expression of TLR7 was found in FLS from JIA patients. Interpretation & conclusion: TLR pathway stimulation by microbial products or endogenous ligands could be involved in the production of MMPs in JIA and may contribute to disease pathology. Thus it may be beneficial to inhibit TLR pathway to reduce cartilage destruction.

Artritis idiopática juvenil: parte 1: diagnóstico, patogenia y manifestaciones clínicas / Juvenil idiopathic arthritis: part 1: diagnosis, pathogenesis and clinical manifestations

La artritis idiopática juvenil no constituye una entidad “única” sino un grupo heterogéneo de enfermedades o trastornos inflamatorios. Esta nueva denominación abarca diferentes categorías de enfermedad, cada una de ellas con distintas formas de presentación, signos y síntomas clínicos, y pronóstico. La causa de esta entidad es aún desconocida, pero factores ambientales y genéticos intervienen en su patogenia. Es la más común de las enfermedades reumáticas en la infancia y causa importante de discapacidad a corto y largo plazos. Revisaremos aquí las manifestaciones clínicas, la nueva clasificación, el abordaje diagnóstico y los diagnósticos diferenciales.

Juvenile idiopathic arthritis is not a single disease and constitutes an heterogeneous group of illnesses or inflammatory disorders. This new nomenclature encompasses different disease categories, each of which has different presentation, clinical signs, symptoms, and outcome. The cause of the disease is still unknown but both environmental and genetic factors seem to be related to its pathogenesis. Is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability.In this article, clinical manifestation, new classification and approach to diagnosis are reviewed.

Interleucina-18 em pacientes com artrite idiopática juvenil: um marcador de atividade e gravidade de doença / Interleukin-18 as a maker of disease activity and severity in juvenile idiopathic athritis patients

Com o intuito de verificar a importância da IL-18 na patogênese da artrite idiopática juvenil (AIJ) foram mensurados os níveis de IL-18 no líquido sinovial (LS) e soro de 50 pacientes, sua correlação com parâmetros de atividade e gravidade de doença foi determinada. Os níveis de IL-1, IL-1Ra, IL-6 e IL-18 foram mais elevados no soro dos pacientes que nos controles. Os níveis de IL-18 do soro não diferiram dos níveis do LS, e ambos se correlacionaram positivamente com PCR, articulações ativas, escore radiológico e IL-1, IL-1Ra e IL-6 / In order to verify the importance of IL-18 in the pathogenesis of juvenile idiopathic arthritis (JIA) we measured IL-18 levels in synovial fluid (SF) and serum of 50 patients and their correlation with parameters of disease activity and severity was determined. The levels of IL-1, IL-1Ra, IL-6 and IL-18 were higher in patient’s sera than in controls. SF levels of IL-18 didn’t differ from those of serum. The levels of IL-18 (SF and serum) positively correlated with: CRP, active joints, radiological score and with IL-1, IL1Ra and IL-6...

Estudo artroscópico em joelhos de pacientes portadores de artrite reumatóide juvenil do tipo pauciarticular / Arthroscopic study in knees of patients with pauciarticular juvenile rheumatoid arthritis

Os autores estudaram nove pacientes portadores de artrite reumatóide juvenil do tipo pauciarticular, submetidos a artroscopia de joelho, com seguimento médio de 16,5 meses (6 a 54 meses). No estudo morfológico, enfatizaram as diferentes formas de reaçäo sinovial, como também seu padräo heterogênio de distribuiçäo. Näo encontraram relaçäo entre o grau das lesöes condrais e a intensidade da inflamaçäo sinovial. Näo foi encontrada no exame anatomopatológico característica de processo inflamatório agudo. Através da imunofluorescência, detectaron-se depósitos de imunoglobulinas na membrana sinovial e na cartilagem articular. Nesta pesquisa foi valorizada a importância da artroscopia no diagnóstico da artrite reumatóide juvenil do tipo pauciarticular

Mielograma en artritis reumatoidea juvenil sistémica / Myelogram in systemic juvenile rheumatoid arthritis

Se revisaron en forma retrospectiva mielogramas correspondientes a 7 pacientes con artritis reumatoidea juvenil sistémica. Se encontró eosinofilia y monocitosis en todos los pacientes, en tanto que había aumento de mononucleares basófilos en 5 de ellos. Estos dos últimos hallazgos demuestran activación del sistema mononuclear fagocitario. La hipoplasia eritroide es multifacatorial en esta enfermedad del tejido conectivo y se encontró en 6 pacientes, en tanto que 4 tenían aumento de células plasmáticas y 3 hemofagia, la cual no encontramos descrita previamente

Biopsia sinovial percutânea na avaliaçäo diagnóstica do paciente reumatológico / Percutaneous synovial biopsy for the diagnostic evaluation of the patient with rheumatic diseases

Quarenta e sete biopsias nsinoviais percutâneas efetuadas em 22 pacientes com doença reumatóide, sendo quatro com a forma juvenil, 13 com poliartrite e 12 com monoartrite näo definidas, foram avaliadas. Os achados anátomo-patológicos confirmaram as evidências clínicas em 76% dos pacientes com doença reumatóide ou doença reumatoide juvenil; sugeriram diagnóstico de doença reumatóide em 80% dos pacientes com poliartrite e em dois casos de monoartrite indefinidas; evidenciaram a presença de bacilos álcool-ácidos resistentes em dois e granuloma em um dos casos de monoartrite. Em vista de tais resultados, achamos que a biopsia sinovial percutânea possa auxiliar na proprdêutica diagnóstica dos pacientes com poli/monoartrites näo definidas