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1.
Clin Immunol ; 248: 109270, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36806704

RESUMO

OBJECTIVES: To validate the correlation between laboratory markers reflecting disease activity of macrophage activation syndrome (MAS) and serum cytokine levels and identify the valuable laboratory markers that change over time for a prompt MAS diagnosis. METHODS: Serum cytokine levels were determined by enzyme-linked immunosorbent assay and compared with laboratory markers reflecting MAS disease activity.The changes in values were evaluated from the acute phase of systemic juvenile idiopathic arthritis (s-JIA) to MAS diagnosis. RESULTS: CXCL9 was significantly correlated with aspartate aminotransferase (AST), lactate dehydrogenase (LDH), D dimer, and urine ß2 microglobulin levels. sTNF-RII was significantly correlated with platelet counts, AST, LDH, D dimer, and ferritin levels. Significant changes in platelet count, LDH, and D dimer levels were observed. Decreased platelet counts were the most valuable indicator for MAS diagnosis. CONCLUSION: Monitoring the laboratory markers that change over time, particularly decreased platelet counts, was valuable for the prompt MAS diagnosis in s-JIA.


Assuntos
Artrite Juvenil , Síndrome de Ativação Macrofágica , Humanos , Citocinas , Síndrome de Ativação Macrofágica/etiologia , Biomarcadores , Produtos de Degradação da Fibrina e do Fibrinogênio , Ativação de Macrófagos
2.
Cytokine ; 169: 156280, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37356260

RESUMO

OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.


Assuntos
Citocinas , Síndrome de Linfonodos Mucocutâneos , Choque Séptico , Síndrome de Resposta Inflamatória Sistêmica , Infecções por Yersinia pseudotuberculosis , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Citocinas/sangue , Humanos , Interleucina-6/sangue , Quimiocina CXCL9/sangue , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/diagnóstico , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Diagnóstico Diferencial , Choque Séptico/sangue , Choque Séptico/diagnóstico , Infecções por Yersinia pseudotuberculosis/sangue , Infecções por Yersinia pseudotuberculosis/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
3.
Am J Med Genet A ; 191(11): 2736-2742, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37658587

RESUMO

In this retrospective cohort study, we investigated the impact of tracheostomies on the long-term survival of children with trisomy 13 syndrome at a Japanese tertiary pediatric center. We compared survival and survival to discharge rates between patients who underwent tracheostomies during their NICU stays (T group, n = 8) and those who did not (non-T group, n = 11). A total of 19 patients enrolled. Median survival in all patients was 673 (266-1535) days. Significant differences in the 1-, 2-, and 3-year survival rates were found between the T and the non-T groups (100% vs. 46%, p = 0.018; 88% vs. 18%, p = 0.006; 63% vs. 9%, p = 0.041, respectively). The survival to discharge rate was higher in the T versus non-T group (75% vs. 45%, p = 0.352). This study highlights a significantly higher long-term survival of patients with trisomy 13 syndrome who underwent tracheostomies during their NICU stays.

4.
Mod Rheumatol ; 33(5): 1021-1029, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36112493

RESUMO

OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.


Assuntos
Artrite Juvenil , Dermatomiosite , Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Reumatologia , Síndrome de Sjogren , Criança , Humanos , Masculino , Feminino , Doenças Reumáticas/epidemiologia , Dermatomiosite/diagnóstico , Dermatomiosite/epidemiologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Japão/epidemiologia , Artrite Juvenil/epidemiologia , Sistema de Registros , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia
5.
Am J Med Genet A ; 188(4): 1048-1055, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34889030

RESUMO

The effects of medical and surgical interventions on the survival of patients with trisomy 18 have been reported, leading to changes in perinatal management and decision-making. However, few studies have fully reported the recent changes in survival and treatment of trisomy 18. We examined how treatment and survival of patients with trisomy 18 have changed over a decade in a Japanese pediatric tertiary referral center. This retrospective cohort study included patients with trisomy 18 who were admitted within the first 7 days of life at the Hyogo Prefectural Kobe Children's Hospital between 2008 and 2017. The patients were divided into early period (EP) and late period (LP) groups based on the birth year of 2008-2012 and 2013-2017, respectively. Changes in treatment and survival rates were compared between the two groups. A total of 56 patients were studied (29 in the EP group and 27 in the LP group). One-year survival rates were 34.5% and 59.3% in the EP and LP groups, respectively. The survival to discharge rate significantly increased from 27.6% in the EP group to 81.5% in the LP group (p < 0.001). The proportion of patients receiving surgery, especially for congenital heart defects, significantly increased from 59% in the EP group to 96% in the LP group (p = 0.001). In our single-center study, survival and survival to discharge were significantly improved in patients with trisomy 18, probably because of increased rate of surgical interventions. These findings may facilitate better decision-making by patients' families and healthcare providers.


Assuntos
Cardiopatias Congênitas , Criança , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Alta do Paciente , Gravidez , Estudos Retrospectivos , Taxa de Sobrevida , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genética
6.
Rheumatology (Oxford) ; 60(5): 2421-2426, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33200207

RESUMO

OBJECTIVE: To investigate the clinical significance of serum IL-18 levels for the diagnosis of systemic JIA (s-JIA) and to predict the disease course of s-JIA. METHODS: Overall, 116 patients with s-JIA, 151 with other diseases and 20 healthy controls were analysed. Serum IL-18 levels were measured longitudinally in 41 patients with s-JIA from active phase through remission phase. Serum IL-18 levels were quantified via enzyme-linked immunosorbent assay and the results were compared with clinical features and the disease course of s-JIA. RESULTS: The serum IL-18 level cut-off value for differentiation of s-JIA from other diseases was 4800 pg/ml. In patients with a monocyclic course, serum IL-18 levels steadily decreased during the inactive phase and low levels were sustained during remission. In contrast, in patients with a chronic course, elevated serum IL-18 levels were sustained even during the inactive phase. In patients with a polycyclic course, serum IL-18 levels were elevated during disease flares and normalized during the inactive phase. The serum IL-18 level cut-off value for diagnosis of remission in s-JIA was 595 pg/ml. CONCLUSION: Serum IL-18 levels of >4800 pg/ml may be useful for differentiating between s-JIA and other diseases. Monitoring of serum IL-18 levels might be useful for predicting the disease course and assessing remission in s-JIA.


Assuntos
Artrite Juvenil/diagnóstico , Interleucina-18/sangue , Adolescente , Artrite Juvenil/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Masculino , Prognóstico
7.
Rheumatology (Oxford) ; 60(1): 231-238, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32681176

RESUMO

OBJECTIVES: To compare the cytokines involved in the development of macrophage activation syndrome (MAS) in different background rheumatic diseases and to identify serum biomarkers for MAS diagnosis. METHODS: Serum neopterin, IL-6, IL-18 and soluble TNF receptor (sTNFR) type I (sTNFR-I) and type II (sTNFR-II) levels were determined using ELISA in 12 patients with SLE, including five with MAS; 12 patients with JDM, including four with MAS; 75 patients with Kawasaki disease (KD), including six with MAS; and 179 patients with systemic JIA (s-JIA), including 43 with MAS. These results were compared with the clinical features of MAS. RESULTS: Serum neopterin, IL-18 and sTNFR-II levels were significantly higher during the MAS phase than during the active phase in patients with all diseases. Furthermore, serum sTNFR-I levels were significantly higher during the MAS phase than during the active phase in patients with SLE, KD and s-JIA. Receiver operating characteristic (ROC) curve analysis revealed that serum sTNFR-I levels for SLE, serum IL-18 levels for JDM, and serum sTNFR-II levels for KD and s-JIA had the highest areas under the ROC curve. Serum levels of these cytokines were significantly and positively correlated with serum ferritin levels. CONCLUSIONS: Overproduction of IFN-γ, IL-18 and TNF-α might be closely related to the development of MAS. Serum levels of sTNFR-I for SLE, IL-18 for JDM, and sTNFR-II for KD and s-JIA might be useful diagnostic markers for the transition from active phase to MAS.


Assuntos
Síndrome de Ativação Macrofágica/sangue , Doenças Reumáticas/complicações , Adolescente , Artrite Juvenil/sangue , Artrite Juvenil/diagnóstico , Biomarcadores/sangue , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Humanos , Interferon gama/sangue , Interleucina-18/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/etiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Neopterina/sangue , Curva ROC , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue
8.
Pediatr Res ; 88(6): 934-939, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32184444

RESUMO

BACKGROUND: To compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA) during tocilizumab therapy. METHODS: Serum cytokine levels of neopterin, IL-18, C-X-C motif chemokine ligand 9, soluble tumor necrosis factor receptor (sTNFR)-I, and sTNFR-II were determined by enzyme-linked immunosorbent assay in 36 patients with MAS complicating s-JIA including 12 patients receiving tocilizumab. Furthermore, the serum sTNFR-II/I ratio was compared with the clinical features of MAS. RESULTS: The levels of all serum cytokines at MAS diagnosis were significantly lower in the tocilizumab-treated group than in the tocilizumab-untreated group. In contrast, the serum sTNFR-II/I ratio at MAS diagnosis was comparable between the tocilizumab-treated and the tocilizumab-untreated groups. The receiver operating characteristic curve analysis revealed that the area under the curve and cut-off values of sTNFR-II/I ratio were 0.9722 and 4.71, respectively. The serum sTNFR-II/I ratio, which was significantly elevated in patients with MAS complicating s-JIA, was correlated positively with disease activity. CONCLUSIONS: These findings suggest that the serum sTNFR-II/I ratio might be a useful indicator to evaluate disease activity in MAS complicating s-JIA and a useful diagnostic marker for the transition from active-phase s-JIA to MAS even in tocilizumab-treated patients. IMPACT: This is the first study to analyze the role of tocilizumab in modifying the serum levels of biomarkers used for the diagnosis of MAS complicating s-JIA. We found the biomarker for the diagnosis of MAS complicating s-JIA during tocilizumab therapy. We hope our results might be useful for the development of a new criteria for the diagnosis of MAS complicating s-JIA in patients treated with tocilizumab in future.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Artrite Juvenil/sangue , Biomarcadores/sangue , Síndrome de Ativação Macrofágica/sangue , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Quimiocina CXCL9/sangue , Criança , Pré-Escolar , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inflamação , Interferon gama/metabolismo , Interleucina-18/sangue , Síndrome de Ativação Macrofágica/complicações , Síndrome de Ativação Macrofágica/diagnóstico , Masculino , Curva ROC , Receptores Tipo II do Fator de Necrose Tumoral/sangue
9.
Clin Immunol ; 208: 108252, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31449879

RESUMO

Our study aimed to compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Serum cytokine levels (neopterin, IL-18, and CXCL9 and soluble tumor necrosis factor receptor type I (sTNFR-I) and II) were determined by enzyme-linked immunosorbent assay in 78 patients with s-JIA, including 21 with MAS. Receiver operating characteristic curve analysis revealed area under the curve values and cut off values of neopterin, IL-18, CXCL9, sTNFR-II/I ratio and ferritin were 0.9465/19.5 nmol/l, 0.8895/69250 ng/ml, 0.9333/3130 pg/ml, 0.9395/3.796 and 0.8671/2560 ng/ml, respectively. Serum neopterin levels were significantly elevated in patients with MAS and those were correlated positively with disease activity. In conclusion, serum neopterin levels may be used as a promising indicator of disease activity in s-JIA and MAS and for evaluating it. It may also be a useful marker to diagnose the transition to MAS from active-phase s-JIA.


Assuntos
Artrite Juvenil/sangue , Artrite Juvenil/complicações , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/etiologia , Neopterina/sangue , Biomarcadores/sangue , Criança , Feminino , Humanos , Masculino
10.
Clin Immunol ; 208: 108255, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31476438

RESUMO

The present study employed an antibody array that simultaneously detects 174 cytokines to identify cytokines involved in the development of macrophage activation syndrome (MAS) associated with systemic lupus erythematosus (SLE) with a view to elucidating potential predictive markers. Eight SLE patients, including four with MAS, were analyzed. Levels of 31 cytokines were significantly elevated in the MAS phase compared with those in the active phase of SLE. Among these cytokines, the MAS/active phase ratios of CXCL9 and soluble tumor necrosis factor receptor II (sTNFR-II) were highest. Elevated serum CXCL9 and sTNFR-II levels during the MAS phase were confirmed by ELISA and were strongly correlated with other inflammatory markers, reflecting the disease activity of MAS associated with SLE. These results highlight the clinical significance of serum CXCL-9 and sTNFR-II levels, and indicate they may be useful biomarkers for the diagnosis of MAS associated with SLE.


Assuntos
Biomarcadores/sangue , Lúpus Eritematoso Sistêmico/complicações , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/etiologia , Adolescente , Quimiocina CXCL9/sangue , Criança , Feminino , Humanos , Masculino , Receptores Tipo II do Fator de Necrose Tumoral/sangue
11.
Cytokine ; 119: 182-187, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30952065

RESUMO

To clarify cytokines involved in the development of systemic juvenile idiopathic arthritis (s-JIA) associated macrophage activation syndrome (MAS) and to identify the serum biomarkers for the diagnosis of s-JIA associated MAS, we employed an antibody array that simultaneously detects 174 cytokines. Fifteen s-JIA patients including 5 patients receiving tocilizumab (TCZ) were analyzed. The levels of five cytokines were significantly elevated in MAS phase compared to those in the active phase of s-JIA. CXCL9 showed the most significant increase following the development of s-JIA associated MAS. Next, to confirm clinical significance of serum CXCL9 levels as a biomarker for s-JIA associated MAS, serum CXCL9 levels in 56 patients with s-JIA including 20 with MAS were analyzed. Results were compared with the clinical features of s-JIA associated MAS. Serum CXCL9 levels correlated positively with disease activity. Monitoring of serum CXCL9 is useful for the evaluation of disease activity in s-JIA associated MAS.


Assuntos
Artrite Juvenil/sangue , Biomarcadores/sangue , Quimiocina CXCL9/sangue , Síndrome de Ativação Macrofágica/sangue , Ativação de Macrófagos/fisiologia , Adolescente , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Humanos , Lactente , Ativação de Macrófagos/efeitos dos fármacos , Síndrome de Ativação Macrofágica/tratamento farmacológico , Masculino
12.
Cytokine ; 110: 459-465, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29801971

RESUMO

This study aims to investigate the clinical significance of serum soluble CD163 (sCD163) levels as a predictor of the disease activity of systemic juvenile idiopathic arthritis (s-JIA). In this study, we examined 63 patients with s-JIA, four with Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis (EBV-HLH), and seven with Kawasaki disease (KD), along with 14 healthy controls. We quantified serum cytokine levels (sCD163, neopterin, IL-18, IL-6) by enzyme-linked immunosorbent assay and compared the results with the clinical features of s-JIA. Serum sCD163 levels were significantly elevated in patients with s-JIA associated macrophage activation syndrome (MAS) and EBV-HLH compared to those in patients with acute-phase s-JIA and KD. In addition, serum sCD163 levels profoundly increased with the progress of MAS and correlated positively with the disease activity of s-JIA, even in patients receiving tocilizumab. Furthermore, serum sCD163 levels significantly decreased in the inactive phase compared to those in the active phase and normalized in remission. The correlation between macrophage activation and serum sCD163 levels might be a unique indicator of the disease activity and a potential diagnostic laboratory criterion for clinical remission in patients with s-JIA, including those receiving tocilizumab.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Artrite Juvenil/sangue , Biomarcadores/sangue , Herpesvirus Humano 4/patogenicidade , Ativação de Macrófagos/fisiologia , Receptores de Superfície Celular/sangue , Anticorpos Monoclonais Humanizados/farmacologia , Artrite Juvenil/tratamento farmacológico , Criança , Citocinas/sangue , Feminino , Humanos , Interleucina-18/sangue , Interleucina-6/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/virologia , Ativação de Macrófagos/efeitos dos fármacos , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/virologia , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/virologia , Neopterina/farmacologia
14.
Mod Rheumatol ; 28(5): 826-831, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29293033

RESUMO

OBJECTIVE: To estimate target of treatment for long-term efficacy of the first biologic agent used to treat polyarticular juvenile idiopathic arthritis (pJIA). METHODS: A retrospective cohort of patients with pJIA treated at six medical institutions in Japan between 1 March 2005 and 31 October 2014 was identified. The patients were divided by 2-year treatment periods with the first biologic agent into continuous treatment group and switching group. Three markers were examined: matrix metalloproteinase-3 (MMP-3), erythrocyte sedimentation rate (ESR), and disease activity score (DAS) 28-ESR. RESULTS: Thirty-two pJIA patients (8 boys, 24 girls) from 43 recruited patients were included in this study. The treatment periods with the first biologic agent in continuous treatment group (24 patients, 75%) was 40 months (median, range 24-119) and switching group (8 patients; 25%) was 9.5 months (median, 6-18). Markers [odds ratio (95% confidence interval)] at 3 months were MMP-3 [1.02 (0.99-1.05), p = .219], ESR [1.00 (0.78-1.30), p = .998], and DAS28-ESR [13.9 (2.08-409.82), p = .035]. The cut-off point for DAS28-ESR at 3 months to distinguish the two groups was 2.49 (sensitivity, 87.5%; specificity, 87.5%). CONCLUSION: DAS28-ESR of 2.49 at 3 months after initiating the first biologic agent can be a target of sustained treatment in pJIA patients.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Adolescente , Artrite Juvenil/sangue , Biomarcadores/sangue , Sedimentação Sanguínea , Criança , Feminino , Humanos , Masculino , Metaloproteinase 3 da Matriz/sangue
18.
Mod Rheumatol ; 27(5): 833-837, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28094589

RESUMO

OBJECTIVES: To assess the role of leucine-rich α2-glycoprotein (LRG) as a biomarker for monitoring systemic juvenile idiopathic arthritis (s-JIA) disease activity during interleukin (IL)-6 blockade treatment. METHODS: We serially measured serum LRG levels in four s-JIA patients treated with the anti-IL-6 receptor antibody tocilizumab and determined the correlation between clinical symptoms and other inflammatory biomarkers and proinflammatory cytokines, including IL-18, IL-6, neopterin, and tumor necrosis factor-α receptor type I and II. The serum levels of LRG and proinflammatory cytokines were determined using enzyme-linked immunosorbent assay. RESULTS: Serum LRG levels increased concomitantly with s-JIA disease flare-up and macrophage activation syndrome development. Furthermore, even in the clinically inactive phase, serum LRG levels were well above normal values. There were no correlations between serum LRG levels and indicators of s-JIA disease activity other than aspartate aminotransferase. There were significant positive correlations between serum LRG levels and proinflammatory cytokines. CONCLUSIONS: Serum LRG levels might be a unique and potential biomarker of s-JIA disease activity during IL-6 blockade treatment.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Artrite Juvenil , Glicoproteínas/análise , Interleucina-6/antagonistas & inibidores , Proteínas de Fase Aguda/análise , Adolescente , Anticorpos Monoclonais Humanizados/imunologia , Antirreumáticos/administração & dosagem , Antirreumáticos/imunologia , Artrite Juvenil/diagnóstico , Artrite Juvenil/imunologia , Biomarcadores/análise , Criança , Pré-Escolar , Citocinas/análise , Feminino , Humanos , Síndrome de Ativação Macrofágica/etiologia , Síndrome de Ativação Macrofágica/imunologia , Masculino , Gravidade do Paciente , Reprodutibilidade dos Testes , Estatística como Assunto , Exacerbação dos Sintomas
19.
Mod Rheumatol ; 27(4): 609-613, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27785924

RESUMO

OBJECTIVE: To investigate clinical usefulness of serum interleukin (IL)-33 levels as an indicator of disease activity in juvenile idiopathic arthritis (JIA). METHODS: We measured serum levels of IL-33 in 39 patients with JIA, including 7 patients with rheumatoid factor positive poly-JIA (RF + poly-JIA), 8 patients with RF negative poly-JIA (RF-poly-JIA), 20 patients with oligoarticular JIA (Oligo-JIA), 4 patients with enthesitis-related arthritis (ERA) and 30 age-matched healthy controls. Furthermore, we determined their correlation with measures of disease activity. RESULTS: Serum IL-33 levels in patients with RF + poly-JIA were significantly elevated compared to those in patients with RF-poly-JIA, oligo-JIA and HC. Serum IL-33 levels in patients with RF-poly-JIA, oligo-JIA and ERA were not elevated compared to those in HC. Serum IL-33 levels in RF + poly-JIA patients normalized in remission phase. Serum IL-33 levels correlated positively with RF in patients with RF + poly-JIA. CONCLUSIONS: These results indicate that serum IL-33 levels in RF + poly-JIA patients correlated with disease activity, suggesting a potential role of IL-33 as a promising indicator of disease activity.


Assuntos
Artrite Juvenil/sangue , Interleucina-33/sangue , Fator Reumatoide/sangue , Adolescente , Biomarcadores/sangue , Criança , Feminino , Humanos , Masculino
20.
Cytokine ; 80: 1-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26908294

RESUMO

To assess the role of angiopoietin (Ang)-1 and Ang-2 and to investigate the clinical significance of serum levels of them in systemic juvenile idiopathic arthritis (s-JIA)-associated macrophage activation syndrome (MAS), we determined these levels in 51 patients with s-JIA, 11 patients with polyarticular JIA (poly-JIA), 12 patients with virus associated hemophagocytic syndrome (VAHS), 12 patients with Kawasaki disease (KD), and 15 age-matched healthy controls (HC). The results were compared with clinical features of MAS. During the MAS phase, serum Ang-1 levels were significantly decreased compared with those during the active and inactive phases. Serum Ang-2/1 ratio were significantly elevated during the MAS phase, compared with those during the active and inactive phases. There was a rapid increase in the Ang-2/1 ratio at the onset of MAS. Serum Ang-1 and the Ang-2/1 ratio significantly correlated with measures of disease activity, including AST and LDH. Ang-2/1 dysregulation was also observed in patients with VAHS, whereas not observed in most cases of KD. The homeostasis of vascular endothelial function by Ang-1 and Ang-2 is disrupted in MAS. Serum Ang-1 levels and the Ang-2/1 ratio might represent promising indicators of disease activity for MAS.


Assuntos
Angiopoietina-1/sangue , Angiopoietina-2/sangue , Artrite Juvenil/imunologia , Endotélio Vascular/fisiologia , Homeostase , Síndrome de Ativação Macrofágica/fisiopatologia , Adolescente , Angiopoietina-1/fisiologia , Angiopoietina-2/fisiologia , Artrite Juvenil/complicações , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Linfo-Histiocitose Hemofagocítica/virologia , Síndrome de Ativação Macrofágica/etiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/fisiopatologia
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