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1.
Arthritis Rheumatol ; 71(11): 1943-1954, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31379071

RESUMO

OBJECTIVE: Systemic juvenile idiopathic arthritis (JIA) is associated with a recently recognized, albeit poorly defined and characterized, lung disease (LD). The objective of this study was to describe the clinical characteristics, risk factors, and histopathologic and immunologic features of this novel inflammatory LD associated with systemic JIA (designated SJIA-LD). METHODS: Clinical data collected since 2010 were abstracted from the medical records of patients with systemic JIA from the Cincinnati Children's Hospital Medical Center. Epidemiologic, cellular, biochemical, genomic, and transcriptional profiling analyses were performed. RESULTS: Eighteen patients with SJIA-LD were identified. Radiographic findings included diffuse ground-glass opacities, subpleural reticulation, interlobular septal thickening, and lymphadenopathy. Pathologic findings included patchy, but extensive, lymphoplasmacytic infiltrates and mixed features of pulmonary alveolar proteinosis (PAP) and endogenous lipoid pneumonia. Compared to systemic JIA patients without LD, those with SJIA-LD were younger at the diagnosis of systemic JIA (odds ratio [OR] 6.5, P = 0.007), more often had prior episodes of macrophage activation syndrome (MAS) (OR 14.5, P < 0.001), had a greater frequency of adverse reactions to biologic therapy (OR 13.6, P < 0.001), and had higher serum levels of interleukin-18 (IL-18) (median 27,612 pg/ml versus 5,413 pg/ml; P = 0.047). Patients with SJIA-LD lacked genetic, serologic, or functional evidence of granulocyte-macrophage colony-stimulating factor pathway dysfunction, a feature that is typical of familial or autoimmune PAP. Moreover, bronchoalveolar lavage (BAL) fluid from patients with SJIA-LD rarely demonstrated proteinaceous material and had less lipid-laden macrophages than that seen in patients with primary PAP (mean 10.5% in patients with SJIA-LD versus 66.1% in patients with primary PAP; P < 0.001). BAL fluid from patients with SJIA-LD contained elevated levels of IL-18 and the interferon-γ-induced chemokines CXCL9 and CXCL10. Transcriptional profiling of the lung tissue from patients with SJIA-LD identified up-regulated type II interferon and T cell activation networks. This signature was also present in SJIA-LD human lung tissue sections that lacked substantial histopathologic findings, suggesting that this activation signature may precede and drive the lung pathology in SJIA-LD. CONCLUSION: Pulmonary disease is increasingly detected in children with systemic JIA, particularly in association with MAS. This entity has distinct clinical and immunologic features and represents an uncharacterized inflammatory LD.


Assuntos
Artrite Juvenil/epidemiologia , Proteinose Alveolar Pulmonar/epidemiologia , Distribuição por Idade , Artrite Juvenil/diagnóstico por imagem , Artrite Juvenil/imunologia , Artrite Juvenil/patologia , Líquido da Lavagem Broncoalveolar , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/metabolismo , Criança , Pré-Escolar , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Lactente , Interferon gama/metabolismo , Interleucina-18/imunologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias/diagnóstico por imagem , Pneumopatias/epidemiologia , Pneumopatias/imunologia , Pneumopatias/patologia , Síndrome de Ativação Macrofágica/epidemiologia , Síndrome de Ativação Macrofágica/imunologia , Masculino , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/imunologia , Proteinose Alveolar Pulmonar/patologia , Linfócitos T/metabolismo , Tomografia Computadorizada por Raios X , Transcriptoma , Regulação para Cima
2.
Pediatr Rheumatol Online J ; 17(1): 33, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266504

RESUMO

BACKGROUND: The etiology of Juvenile Idiopathic Arthritis (JIA) is poorly understood. The purpose of this study was to examine the possible influence of early nutrition on later development of JIA. METHODS: In a population-based prospective birth cohort of 15,740 children we collected nutritional data, including fish consumption, and biological samples during pregnancy, at birth and at different ages. 16 years after study inclusion we identified 42 children with JIA, of whom 11 were positive for Antinuclear Antibodies (ANA). Heavy metals were analysed in cord blood of all 42 JIA patients and 40 age and sex-matched controls. A multivariable logistic regression model, adjusted for relevant factors, was used as well as Mann-Whitney U-test. RESULTS: Fish consumption more than once a week during pregnancy as well as during the child's first year of life was associated with an increased risk of JIA (aOR 4.5 (1.95-10.4); p < 0.001 and aOR 5.1 (2.1-12.4) p < 0.001) and of ANA-positivity (aOR 2.2 (1.4-3.6); p = 0.002 and p < 0.001). Concentrations of Al, Cd, Hg and Li in cord blood were significantly higher in the JIA-group than in controls. The ANA-positive, all of whom had consumed fish >once/week their first year, had significantly higher concentrations of Al (p < 0.001), Cd (p = 0.003), and Li (p < 0.001) in cord blood than controls. Frequency of fish consumption correlated with concentrations of Cd (p = 0.003), Li (p = 0.015) and Hg (p = 0.011). CONCLUSIONS: Moderate exposure to heavy metals, associated with fish consumption, during pregnancy and early childhood may cause effects on the immune system of the offspring, resulting in ANA positivity and JIA.


Assuntos
Artrite Juvenil/imunologia , Autoimunidade/fisiologia , Metais Pesados/efeitos adversos , Adolescente , Animais , Anticorpos Antinucleares/metabolismo , Criança , Pré-Escolar , Dieta/efeitos adversos , Feminino , Sangue Fetal/química , Peixes/imunologia , Peixes/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Metais Pesados/metabolismo , Linhagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia , Estudos Prospectivos , Fatores de Risco
3.
Int J Rheum Dis ; 22(9): 1661-1669, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273940

RESUMO

AIM: Systemic juvenile idiopathic arthritis (sJIA) is a distinctive subtype of JIA characterized by systemic features and poor outcome. We aimed to investigate demographic and clinical features, long-term treatment response and disease complications in a large sJIA cohort. METHODS: Patients diagnosed with sJIA followed up at a pediatric rheumatology outpatient department from January 2003 to December 2017 were included. Demographic and clinical features, long-term treatment response and disease complications were retrospectively collected. RESULTS: A total of 168 sJIA patients (51.8% female, 48.2% male) were included: 31.5% with monocyclic, 13.7% polycyclic and 54.8% with persistent clinical course. Corticosteroids were initially used in all patients. Methotrexate was used in 75% and cyclosporine A was used in 17.3% patients. Biological drugs were used in 42.8% patients; etanercept in 29.7%, anakinra in 16%, canakinumab in 16%, tocilizumab in 10% patients. Remission off medication was achieved in 82 (48.8%). Macrophage activation syndrome (MAS) was present in 11.9%, growth retardation in 11.3% patients. Eight percent (4/50) of patients had low bone mineral density. Three patients (1.78%) died due to MAS secondary multiorgan insufficiency and infection. CONCLUSION: The disease is characterized with diverse clinical presentation and possibly severe complications. MAS complicated with multiorgan insufficiency is the major mortality factor. Corticosteroids represent the mainstay of the initial treatment. In patients resistant to classic treatment, biological drugs should be timely introduced.


Assuntos
Corticosteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Adolescente , Corticosteroides/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Juvenil/diagnóstico , Artrite Juvenil/imunologia , Artrite Juvenil/mortalidade , Produtos Biológicos/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Transtornos do Crescimento/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Síndrome de Ativação Macrofágica/imunologia , Síndrome de Ativação Macrofágica/mortalidade , Masculino , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/mortalidade , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Turquia , Adulto Jovem
4.
Int J Rheum Dis ; 22(8): 1578-1581, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31245900

RESUMO

AIM: To review the clinical features of brachial synovial cyst. METHOD: A case of bilateral brachial synovial cysts is described in a child suffering from systemic juvenile idiopathic arthritis during a relapse. Magnetic resonance imaging and ultrasonography were conducted to further evaluate the nature of the cysts. The case is compared with known cases in a literature review. RESULTS: Review of the literature showed that brachial synovial cysts occur most commonly in systemic juvenile idiopathic arthritis. It is considered that uncontrolled systemic inflammation and recurrent disease activity might be the cause of synovial cysts. CONCLUSION: Brachial synovial cyst is a rare manifestation of juvenile idiopathic arthritis. Uncontrolled systemic inflammation inducing chronic damage to joint structure may be the primary cause of synovial cyst formation.


Assuntos
Artrite Juvenil/complicações , Cisto Sinovial/etiologia , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/imunologia , Criança , Drenagem , Antebraço , Humanos , Masculino , Recidiva , Cisto Sinovial/diagnóstico por imagem , Cisto Sinovial/imunologia , Cisto Sinovial/terapia , Resultado do Tratamento
5.
Autoimmun Rev ; 18(8): 796-804, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31176874

RESUMO

Juvenile idiopathic arthritis (JIA) is a heterogeneous and multifactorial group of chronic arthritis with an onset before the age of 16 years. The pathogenesis of this disease is poorly understood, which makes the distinction among subtypes unclear, delays diagnosis and optimal therapeutic management. MicroRNAs (miRNAs) are small non-coding RNAs that play a critical role in the regulation of immune responses. Their expression is tightly controlled to ensure cellular homeostasis and function of innate and adaptive immune cells. Abnormal expression of miRNAs has been associated with the development of many inflammatory and autoimmune diseases. In this review, we gather results published on miRNAs expression profiles in JIA patients with the aim to identify miRNAs that can be used as diagnostic biomarkers and provide information on disease activity and progression. We also focus on miRNAs deregulated in different forms of JIA to shed light on common pathways potentially involved in disease pathophysiology.


Assuntos
Artrite Juvenil/genética , Artrite Juvenil/imunologia , MicroRNAs/imunologia , Animais , Humanos
6.
Arthritis Rheumatol ; 71(10): 1756-1765, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31131995

RESUMO

OBJECTIVE: Inflamed tissue is characterized by low availability of oxygen and nutrients. Yet CD4+ T helper lymphocytes persist over time in such tissue and probably contribute to the chronicity of inflammation. This study was undertaken to analyze the metabolic adaptation of these cells to the inflamed environment. METHODS: Synovial and blood CD4+ T cells isolated ex vivo from patients with juvenile idiopathic arthritis (JIA) and murine CD4+ T cells were either stimulated once or stimulated repeatedly. Their dependency on particular metabolic pathways for survival was then analyzed using pharmacologic inhibitors. The role of the transcription factor Twist 1 was investigated by determining lactate production and oxygen consumption in Twist1-sufficient and Twist1-deficient murine T cells. The dependency of these murine cells on particular metabolic pathways was analyzed using pharmacologic inhibitors. RESULTS: Programmed death 1 (PD-1)+ T helper cells in synovial fluid samples from patients with JIA survived via fatty acid oxidation (mean ± SEM survival of 3.4 ± 2.85% in the presence of etomoxir versus 60 ± 7.08% in the absence of etomoxir on day 4 of culture) (P < 0.0002; n = 6) and expressed the E-box-binding transcription factor TWIST1 (2-14-fold increased expression) (P = 0.0156 versus PD-1- T helper cells; n = 6). Repeatedly restimulated murine T helper cells, which expressed Twist1 as well, needed Twist1 to survive via fatty acid oxidation. In addition, Twist1 protected the cells against reactive oxygen species. CONCLUSION: Our findings indicate that TWIST1 is a master regulator of metabolic adaptation of T helper cells to chronic inflammation and a target for their selective therapeutic elimination.


Assuntos
Artrite Juvenil/metabolismo , Ácidos Graxos/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Proteína 1 Relacionada a Twist/genética , Animais , Artrite Juvenil/imunologia , Sobrevivência Celular , Metabolismo Energético , Glicólise , Humanos , Inflamação , Ácido Láctico/metabolismo , Camundongos , Proteínas Nucleares/genética , Oxirredução , Consumo de Oxigênio , Receptor de Morte Celular Programada 1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Líquido Sinovial , Linfócitos T Auxiliares-Indutores/imunologia , Células Th1/imunologia , Células Th1/metabolismo , Proteína 1 Relacionada a Twist/metabolismo
7.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999610

RESUMO

Autoinflammatory diseases (AIDs) are heterogeneous disorders characterized by dysregulation in the inflammasome, a large intracellular multiprotein platform, leading to overproduction of interleukin-1(IL-1)ß that plays a predominant pathogenic role in such diseases. Appropriate treatment is crucial, also considering that AIDs may persist into adulthood with negative consequences on patients' quality of life. IL-1ß blockade results in a sustained reduction of disease severity in most AIDs. A growing experience with the human IL-1 receptor antagonist, Anakinra (ANA), and the monoclonal anti IL-1ß antibody, Canakinumab (CANA), has also been engendered, highlighting their efficacy upon protean clinical manifestations of AIDs. Safety and tolerability have been confirmed by several clinical trials and observational studies on both large and small cohorts of AID patients. The same treatment has been proposed in refractory Kawasaki disease, an acute inflammatory vasculitis occurring in children before 5 years, which has been postulated to be autoinflammatory for its phenotypical and immunological similarity with systemic juvenile idiopathic arthritis. Nevertheless, minor concerns about IL-1 antagonists have been raised regarding their employment in children, and the development of novel pharmacological formulations is aimed at minimizing side effects that may affect adherence to treatment. The present review summarizes current findings on the efficacy, safety, and tolerability of ANA and CANA for treatment of AIDs and Kawasaki vasculitis with a specific focus on the pediatric setting.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Deficiência de Mevalonato Quinase/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Artrite Juvenil/imunologia , Síndromes Periódicas Associadas à Criopirina/imunologia , Febre Familiar do Mediterrâneo/imunologia , Febre/imunologia , Doenças Hereditárias Autoinflamatórias/imunologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Interleucina-1beta/imunologia , Deficiência de Mevalonato Quinase/imunologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Receptores de Interleucina-1/antagonistas & inibidores
9.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 37(2): 252-256, Apr.-June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1013282

RESUMO

ABSTRACT Objective: To highlight the importance of the new classification criteria for the macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis in order to reduce morbidity and mortality outcome related to this disease. Case description: A 12-year-old female patient with diagnosis of systemic juvenile idiopathic arthritis under immunosuppression therapy for two years developed cough, acute precordial chest pain, tachypnea, tachycardia and hypoxemia for two days. Chest tomography showed bilateral laminar pleural effusion with bibasilar consolidation. The electrocardiogram was consistent with acute pericarditis and the echocardiogram showed no abnormalities. Laboratory exams revealed anemia, leukocytosis and increased erythrocyte sedimentation rate, as well as C-reactive protein rate and serum biomarkers indicative of myocardial injury. Systemic infection and/or active systemic juvenile idiopathic arthritis were considered. She was treated with antibiotics and glucocorticoids. However, 10 days later she developed active systemic disease (fever, evanescent rash and myopericarditis with signs of heart failure) associated with macrophage activation syndrome, according to the 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. She was treated for five days with pulse therapy, using glucocorticoids, immunoglobulin and cyclosporine A, with improvement of all clinical signs and laboratory tests. Comments: Myopericarditis with signs of heart failure associated with MAS is a rare clinical presentation of systemic juvenile idiopathic arthritis. Macrophage activation syndrome occurs mainly during periods of active systemic juvenile idiopathic arthritis and may be triggered by infection. Knowledge about this syndrome is crucial to reduce morbidity and mortality.


RESUMO Objetivo: Destacar a importância do conhecimento sobre os novos critérios de classificação para síndrome de ativação macrofágica (SAM) na artrite idiopática juvenil sistêmica para reduzir a morbidade e mortalidade desse desfecho. Descrição do caso: Adolescente do sexo feminino de 12 anos de idade, em terapia imunossupressora por diagnóstico de artrite idiopática juvenil sistêmica há 2 anos, com quadro de tosse, dor precordial aguda, taquipneia, taquicardia e hipoxemia há 2 dias. A tomografia de tórax evidenciou efusão pleural laminar bilateral com consolidação bibasal. O eletrocardiograma foi compatível com pericardite aguda, e o ecocardiograma foi normal. Os exames laboratoriais revelaram anemia, leucocitose e aumento da velocidade de hemossedimentação, proteína C-reativa e marcadores séricos de lesão miocárdica. Infecção sistêmica e/ou doença sistêmica em atividade foram consideradas. A paciente foi tratada com antibióticos e glicocorticoide. Entretanto, dez dias depois, evoluiu com doença sistêmica em atividade (febre, exantema e miopericardite com insuficiência cardíaca) associada à SAM, de acordo com o 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis, e necessitou de cinco dias de pulsoterapia com glicocorticoide, imunoglobulina e ciclosporina A, com melhora de todos os parâmetros clínicos e laboratoriais. Comentários: A miopericardite com sinais de insuficiência cardíaca associada à SAM é uma apresentação clínica rara da artrite idiopática juvenil sistêmica, que ocorre principalmente em períodos de atividade sistêmica da doença e pode ser deflagrada por infecções. O conhecimento sobre essa síndrome é fundamental para reduzir morbidade e mortalidade desse grave desfecho.


Assuntos
Humanos , Feminino , Criança , Ciclosporina/administração & dosagem , Glucocorticoides/administração & dosagem , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/fisiopatologia , Artrite Juvenil/imunologia , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Imunoglobulinas Intravenosas/administração & dosagem , Pulsoterapia/métodos , Eletrocardiografia/métodos , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/fisiopatologia , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/terapia , Imunossupressores/administração & dosagem , Leucocitose/diagnóstico , Leucocitose/etiologia
10.
Ann Rheum Dis ; 78(5): 617-628, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30862608

RESUMO

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common class of childhood rheumatic diseases, with distinct disease subsets that may have diverging pathophysiological origins. Both adaptive and innate immune processes have been proposed as primary drivers, which may account for the observed clinical heterogeneity, but few high-depth studies have been performed. METHODS: Here we profiled the adaptive immune system of 85 patients with JIA and 43 age-matched controls with indepth flow cytometry and machine learning approaches. RESULTS: Immune profiling identified immunological changes in patients with JIA. This immune signature was shared across a broad spectrum of childhood inflammatory diseases. The immune signature was identified in clinically distinct subsets of JIA, but was accentuated in patients with systemic JIA and those patients with active disease. Despite the extensive overlap in the immunological spectrum exhibited by healthy children and patients with JIA, machine learning analysis of the data set proved capable of discriminating patients with JIA from healthy controls with ~90% accuracy. CONCLUSIONS: These results pave the way for large-scale immune phenotyping longitudinal studies of JIA. The ability to discriminate between patients with JIA and healthy individuals provides proof of principle for the use of machine learning to identify immune signatures that are predictive to treatment response group.


Assuntos
Imunidade Adaptativa/imunologia , Artrite Juvenil/imunologia , Imunofenotipagem/métodos , Aprendizado de Máquina , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Masculino
11.
Int J Rheum Dis ; 22(7): 1289-1296, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30884197

RESUMO

AIM: The aim of the study was to assess the distribution of human leukocyte antigen (HLA)-B*27 subtypes and its correlation with disease phenotypes in children with enthesitis-related arthritis variant of juvenile idiopathic arthritis (JIA-ERA). METHOD: One hundred and sixty patients (132 males, 28 females) satisfying the International League Against Rheumatism (ILAR) classification criteria for JIA-ERA were assessed and relevant demographic, clinical and radiographic data were documented. HLA-B*27 typing was done for all the patients and B*27 positive samples were subjected to high-resolution gene sequencing. The effect of duration of illness, HLA-B*27, its subtypes, and gender on the clinical phenotype were analyzed. RESULTS: The mean age of disease onset was 12.69 ± 2.4 years with a male:female ratio of 4.7:1.0. HLA-B*27 was positive in 109/160 patients and HLA-B*27:04 was detected in 63% followed by B*27:05 (30%). Duration of illness was greater in patients with skeletal deformity, hip arthritis, sacroiliitis, cervical spine involvement and acute anterior uveitis (AAU) (P < 0.05). HLA-B*27 positivity was associated with a prolonged course of disease, higher incidence of AAU (14.7% vs 2%, P = 0.015), family history of spondyloarthritis (21.1% vs 5.9%; P = 0.015) and higher erythrocyte sedimentation rate as compared to HLA-B*27 negative patients (P < 0.01). The HLA-B*27:04 and *27:05 positive patients had similar clinical phenotypes. CONCLUSION: Presence of HLA-B*27 and long duration of illness results in skeletal deformity, hip arthritis, sacroiliitis, cervical spine involvement and AAU. HLA-B*27:04 followed by B*27:05 are the most common HLA-B*27 subtypes in our study population and both have a similar clinical phenotype.


Assuntos
Artrite Juvenil/genética , Antígeno HLA-B27/genética , Adolescente , Fatores Etários , Artrite Juvenil/diagnóstico , Artrite Juvenil/epidemiologia , Artrite Juvenil/imunologia , Criança , Pré-Escolar , Estudos Transversais , Progressão da Doença , Feminino , Predisposição Genética para Doença , Antígeno HLA-B27/imunologia , Humanos , Índia/epidemiologia , Masculino , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo
12.
Int J Rheum Dis ; 22(7): 1283-1288, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30816022

RESUMO

OBJECTIVE: To clarify the development of juvenile idiopathic arthritis (JIA) to adult-onset autoimmune diseases in a population-based study in Taiwan. METHODS: We analyzed data of 107 433 children born between 1990 and 1997 from the National Taiwan Health Insurance Database. There were 262 JIA patients and 107 171 individuals without JIA who were selected and followed up until December 2013 to investigate their outcomes of adult-onset autoimmune diseases after reaching 16 years of age. The adjusted hazard ratios (aHRs) including 95% confidence intervals (95% CI) of adult-onset autoimmune diseases were calculated using the Cox proportional regression model among different age groups. RESULTS: The incidence rate for patients with a history of JIA was 83.56 per 105 person-months for rheumatoid arthritis (RA), 16.61 for systemic lupus erythematosus (SLE), 58.39 for ankylosing spondylitis (AS), and 33.26 for psoriatic diseases. The aHRs were 29.60 for any autoimmune disease, 129.52 for RA, 10.01 for SLE, 49.62 for AS, and 8.20 for psoriatic diseases. Compared with non-JIA individuals, the aHRs of adult-onset autoimmune diseases were 34.87 (95% CI: 4.85-250.62) at the onset age of 3-5 years, 12.01 (95% CI: 2.99-48.26) at the age of 6-10 years, and 45.80 (95% CI: 29.69-70.64) at the age of 11-15 years. CONCLUSION: Children with JIA were at an increased risk of developing RA, AS, psoriatic disease, and SLE in adulthood.


Assuntos
Artrite Juvenil/epidemiologia , Artrite Reumatoide/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Psoríase/epidemiologia , Espondilite Anquilosante/epidemiologia , Adolescente , Idade de Início , Artrite Juvenil/diagnóstico , Artrite Juvenil/imunologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Psoríase/diagnóstico , Psoríase/imunologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/imunologia , Taiwan , Fatores de Tempo
13.
Front Immunol ; 10: 46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740105

RESUMO

Regulatory T cells (Tregs) are believed to be dysfunctional in autoimmunity. Juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM) result from a loss of normal immune regulation in specific tissues such as joints or muscle and skin, respectively. Here, we discuss recent findings in regard to Treg biology in oligo-/polyarticular JIA and JDM, as well as what we can learn about Treg-related disease mechanism, treatment and biomarkers in JIA/JDM from studies of other diseases. We explore the potential use of Treg immunoregulatory markers and gene signatures as biomarkers for disease course and/or treatment success. Further, we discuss how Tregs are affected by several treatment strategies already employed in the therapy of JIA and JDM and by alternative immunotherapies such as anti-cytokine or co-receptor targeting. Finally, we review recent successes in using Tregs as a treatment target with low-dose IL-2 or cellular immunotherapy. Thus, this mini review will highlight our current understanding and identify open questions in regard to Treg biology, and how recent findings may advance biomarkers and new therapies for JIA and JDM.


Assuntos
Artrite Juvenil/imunologia , Artrite Juvenil/terapia , Dermatomiosite/imunologia , Dermatomiosite/terapia , Imunoterapia Adotiva/efeitos adversos , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Autoimunidade , Biomarcadores , Citocinas/antagonistas & inibidores , Humanos , Camundongos , Resultado do Tratamento
14.
Front Immunol ; 10: 151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30792714

RESUMO

Juvenile Idiopathic Arthritis (JIA) is characterized by a loss of immune tolerance. Here, the balance between the activity of effector T (Teff) cells and regulatory T (Treg) cells is disturbed resulting in chronic inflammation in the joints. Presently, therapeutic strategies are predominantly aimed at suppressing immune activation and pro-inflammatory effector mechanisms, ignoring the opportunity to also promote tolerance by boosting the regulatory side of the immune balance. Histone deacetylases (HDACs) can deacetylate both histone and non-histone proteins and have been demonstrated to modulate epigenetic regulation as well as cellular signaling in various cell types. Importantly, HDACs are potent regulators of both Teff cell and Treg cell function and can thus be regarded as attractive therapeutic targets in chronic inflammatory arthritis. HDAC inhibitors (HDACi) have proven therapeutic potential in the cancer field, and are presently being explored for their potential in the treatment of autoimmune diseases. Specific HDACi have already been demonstrated to reduce the secretion of pro-inflammatory cytokines by Teff cells, and promote Treg numbers and suppressive capacity in vitro and in vivo. In this review, we outline the role of the different classes of HDACs in both Teff cell and Treg cell function. Furthermore, we will review the effect of different HDACi on T cell tolerance and explore their potential as a therapeutic strategy for the treatment of oligoarticular and polyarticular JIA.


Assuntos
Artrite Juvenil/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Linfócitos T/imunologia , Acetilação , Animais , Artrite Juvenil/imunologia , Doença Crônica , Histonas/imunologia , Humanos , Tolerância Imunológica , Inflamação/tratamento farmacológico
15.
Rev Paul Pediatr ; 37(2): 252-256, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30810692

RESUMO

OBJECTIVE: To highlight the importance of the new classification criteria for the macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis in order to reduce morbidity and mortality outcome related to this disease. CASE DESCRIPTION: A 12-year-old female patient with diagnosis of systemic juvenile idiopathic arthritis under immunosuppression therapy for two years developed cough, acute precordial chest pain, tachypnea, tachycardia and hypoxemia for two days. Chest tomography showed bilateral laminar pleural effusion with bibasilar consolidation. The electrocardiogram was consistent with acute pericarditis and the echocardiogram showed no abnormalities. Laboratory exams revealed anemia, leukocytosis and increased erythrocyte sedimentation rate, as well as C-reactive protein rate and serum biomarkers indicative of myocardial injury. Systemic infection and/or active systemic juvenile idiopathic arthritis were considered. She was treated with antibiotics and glucocorticoids. However, 10 days later she developed active systemic disease (fever, evanescent rash and myopericarditis with signs of heart failure) associated with macrophage activation syndrome, according to the 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. She was treated for five days with pulse therapy, using glucocorticoids, immunoglobulin and cyclosporine A, with improvement of all clinical signs and laboratory tests. COMMENTS: Myopericarditis with signs of heart failure associated with MAS is a rare clinical presentation of systemic juvenile idiopathic arthritis. Macrophage activation syndrome occurs mainly during periods of active systemic juvenile idiopathic arthritis and may be triggered by infection. Knowledge about this syndrome is crucial to reduce morbidity and mortality.


Assuntos
Artrite Juvenil , Dor no Peito , Ciclosporina/administração & dosagem , Glucocorticoides/administração & dosagem , Leucocitose , Síndrome de Ativação Macrofágica , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/imunologia , Artrite Juvenil/fisiopatologia , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Criança , Eletrocardiografia/métodos , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunossupressores/administração & dosagem , Leucocitose/diagnóstico , Leucocitose/etiologia , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/fisiopatologia , Síndrome de Ativação Macrofágica/terapia , Pulsoterapia/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
16.
Clin Rheumatol ; 38(6): 1715-1719, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30734215

RESUMO

Recently, an increase in CD163+ macrophages in ileal biopsies from ankylosing spondylitis patients and an increase in intermediate monocytes in enthesitis-related arthritis (ERA) have been reported. Thus, we studied sCD163 levels as M2 macrophage marker in serum and synovial fluid (SF) of ERA children and CD163 expression on monocyte subsets. Serum samples from ERA patients and healthy controls (HC) were assayed for sCD163 (ELISA). Serum and SF from ERA patients were analyzed when available from same patient (paired samples). In 10 patients, the CD163 expression level was analyzed on monocyte subsets by flow cytometry. Results are expressed as median (interquartile range (IQR)). Sera from 85 patients, SF from 32 ERA patients, and serum from 46 HC were analyzed. The average age at inclusion was 16 ± 3.24 years and age at onset was 11.2 ± 2.79 years. Seventy-nine of them were boys and HLA-B27 was positive in 64/80 patients. The median serum sCD163 levels were higher in patients [1080 (1305.2) ng/ml] than HC [780 (812.5) ng/ml; p < 0.001]. The SF levels [9000 (1250) ng/ml] were much higher than serum [3800 (3287.66) ng/ml; p < 0.001]. Disease activity data was available in 56 patients. Mean tender joint count was 2 (3), swollen joint count was 2 (2), ESR was 70 (65) mm and CRP was 7.1 (8.9) mg/dl. Serum sCD163 levels correlated with SF but not with disease activity. Intermediate monocytes (CD14+CD16+) from ERA patients had higher CD163 expression than HC. Elevated sCD163 levels in ERA patient's sera and even higher levels in paired SF suggest towards activation of alternatively activated macrophages in ERA. Lack of correlation with activity may suggest that they have an immune-regulatory role in ERA.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Artrite Juvenil/imunologia , Macrófagos/citologia , Receptores de Superfície Celular/sangue , Sinovite/imunologia , Adolescente , Estudos de Casos e Controles , Feminino , Humanos , Ativação de Macrófagos , Macrófagos/imunologia , Masculino , Monócitos/citologia , Líquido Sinovial/química , Adulto Jovem
17.
Cardiol Young ; 29(3): 435-438, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30681047

RESUMO

The NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome is a rare novel autoinflammatory disorder. Cardiac involvement has not been previously reported. We present a 12-year-old girl with NLRP1-associated autoinflammation with arthritis and dyskeratosis syndrome who was diagnosed with severely impaired left ventricular function and complete left bundle branch block during an exacerbation of the disease. Cardiac dysfunction proved to be rapidly reversible after initiation of high-dose methylprednisolone.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Artrite Juvenil/complicações , Bloqueio de Ramo/etiologia , Disceratose Congênita/complicações , Doenças Hereditárias Autoinflamatórias/complicações , Mutação , Disfunção Ventricular Esquerda/etnologia , Artrite Juvenil/genética , Artrite Juvenil/imunologia , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/fisiopatologia , Criança , Disceratose Congênita/genética , Ecocardiografia , Eletrocardiografia , Feminino , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/imunologia , Humanos , Síndrome , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia
18.
Mod Rheumatol ; 29(2): 275-286, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30686091

RESUMO

Juvenile idiopathic arthritis (JIA) is a chronic childhood arthritis. Its pathogenesis is very complicated, with the involvement of not only immune cells but various types of parenchymal cells, and is affected by both genetic and environmental predispositions. The clinical spectrum from inflammation to related conditions is largely mediated by cytokines including interleukin (IL)-6. Fluctuations in IL-6 and its related molecules can modulate the pathogenesis and the clinical presentation positively or negatively. The recent clinical impact of IL-6 blockade on JIA has begun a therapeutic paradigm shift. This review describes the characteristics of JIA, mainly focused on IL-6 with the current therapeutic perspective.


Assuntos
Artrite Juvenil/imunologia , Interleucina-6/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/imunologia , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/etiologia , Humanos , Interleucina-6/antagonistas & inibidores
19.
Clin Immunol ; 200: 10-15, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30611755

RESUMO

We evaluated the clinical performance of anti-CEP-1 in a Chinese rheumatoid arthritis (RA) cohort. A total of 264 subjects were tested, including 101 RA patients, 38 juvenile idiopathic arthritis (JIA) patients, 46 disease control (DC) and 79 healthy controls (HC). The presence of anti-CEP-1 in patients with RA, JIA, DCs and HC were 61.4%, 13.2%, 15.2% and 5.1%, respectively. Anti-CCP2 demonstrated the highest positive likelihood ratio of 10.11 in the diagnosis of RA, followed by RF (8.88) and anti-CEP-1 (5.82). Anti-CEP-1 positive RA patients displayed significantly higher DAS28 compared to anti-CEP-1 negative RA patients (p = .045). Significant associations were identified between anti-CEP-1 and joint erosions at anti-CEP-1 value of >124.78 U/ml (p = .0026) and between anti-CEP-1 and ILD at anti-CEP-1 value of >185.91 U/ml (p = .0222). Our findings indicate that anti-CEP-1 may not be able to replace anti-CCP2 for routine diagnosis for RA, but they may be helpful for subtyping of the disease.


Assuntos
Anticorpos Anti-Proteína Citrulinada/imunologia , Artrite Reumatoide/imunologia , Grupo com Ancestrais do Continente Asiático , Doenças Pulmonares Intersticiais/imunologia , Fosfopiruvato Hidratase/imunologia , Adolescente , Adulto , Idoso , Artrite Juvenil/imunologia , Autoanticorpos , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/imunologia , Adulto Jovem
20.
Joint Bone Spine ; 86(1): 61-68, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29609005

RESUMO

OBJECTIVES: Programmed cell death-1 (PD-1) and its ligand (PD-L1) mediate negative signal in autoimmune diseases. While little is known about its role in juvenile idiopathic arthritis (JIA). The study aimed to reveal the circulating cell profile and the relative PD-1/PD-L1 expression of JIA subsets, elucidating their underlying immunomodulatory mechanisms. METHODS: We detected the circulating cells and the relative PD-1/PD-L1 signaling in 101 JIA patients and 50 controls by flow cytometry and analyzed their association with disease activity and clinical manifestations. RESULTS: Different from other JIA types, active systemic JIA (sJIA) patients had lower percentage and count of CD4+T cells and lower PD-1 expression on them compared with healthy controls (P<0.05), active polyarthritis (P<0.05) and enthesitis-related arthritis (ERA) patients (P<0.05). Also, they had higher percentage and count of myeloid dendritic cell (mDC) and lower PD-L1 expression on mDC compared with healthy controls (P<0.05). Both PD-1 on CD4+T cell and PD-L1 on mDC were negatively correlated with JADAS-27 in sJIA patients (P<0.05). In addition, PD-1 expression on CD4+T cell was negatively associated with the number of involved joints (P<0.05) and PD-L1 on mDC was lower in patients with fever (P<0.01), which could further divide patients into two groups of different manifestations. CONCLUSIONS: Our finding displayed decreased CD4+T cell, increased mDC and reduced PD-1/PD-L1 signal in sJIA PBMC comparing with other JIA subsets, which might be helpful in JIA differential diagnosis and responsible for distinct clinical manifestations via different mechanisms.


Assuntos
Artrite Juvenil/imunologia , Antígeno B7-H1/biossíntese , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Células Mieloides/imunologia , Receptor de Morte Celular Programada 1/biossíntese , Adolescente , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Masculino , Receptor de Morte Celular Programada 1/imunologia
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