MRP8/14 serum levels as diagnostic markers for systemic juvenile idiopathic arthritis in children with prolonged fever

Rheumatology ◽  
2021 ◽  
Author(s):  
Carolin Park ◽  
María Miranda-Garcia ◽  
Rainer Berendes ◽  
Gerd Horneff ◽  
Jasmin Kuemmerle-Deschner ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Test Performance ◽  
Point Of Care ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Serum Levels ◽  
Sandwich Assay ◽  
Prolonged Fever ◽  
Diagnostic Work ◽  
Work Up ◽  
Systemic Onset

Abstract Objectives Differential diagnosis in children with prolonged fever is challenging. In particular, differentiating systemic-onset juvenile idiopathic arthritis (SJIA) from infectious diseases is difficult. Biomarkers are needed supporting the diagnostic work-up. The aim of this study was to validate the usefulness of MRP8/14 measurements in the diagnostic wok-up of febrile children and transfer it to clinical practice. Methods Data of 1,110 paediatric patients were included and divided into two cohorts: (A) For validation of MRP8/14 test performance with 3 different testing systems: the experimental enzyme-linked immunosorbent sandwich assay (ELISA), commercial ELISA and an innovative (POCT) lateral flow immunoassay (LFIA); (B) to validate the diagnostic accuracy with the two latter assays. Results In cohort A (n = 940), MRP8/14 was elevated in SJIA (12110±2650 ng/ml mean ± 95% CI) compared to other diagnoses (including infections and autoinflammatory diseases; 2980±510 ng/ml) irrespective of fever and anti-inflammatory treatment (p < 0.001). In untreated patients with fever (n = 195) MRP8/14 levels in SJIA (19740±5080 ng/ml) were even higher compared to other diagnoses (4590±1160 ng/ml) (p < 0.001, sensitivity 73%, specificity 90%). In cohort B1, the performance of the tests was confirmed in untreated patients with fever (n = 170): commercial ELISA (sensitivity 79%, specificity 89%) and LFIA (sensitivity 84%, specificity 81%). Compared with ferritin, IL-18, ESR, sIL2-R, and procalcitonin, MRP8/14 showed the best accuracy. Conclusion MRP8/14 serum analyses have been validated as a helpful tool supporting the diagnosis of SJIA in febrile children. The results could be confirmed with commercial ELISA and LFIA enabling a rapid diagnostic point-of-care screening test.

scholarly journals The immunoregulatory function of peripheral blood CD71+ erythroid cells in systemic-onset juvenile idiopathic arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hikaru Kanemasa ◽  
Masataka Ishimura ◽  
Katsuhide Eguchi ◽  
Tamami Tanaka ◽  
Etsuro Nanishi ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Active Phase ◽  
Serum Levels ◽  
Cell Interaction ◽  
Erythroid Cells ◽  
Peripheral Blood Mononuclear ◽  
Systemic Onset

AbstractCD71+ erythroid cells (CECs) are recognized to have an immunoregulatory function via direct cell–cell interaction and soluble mediators. Circulating CECs appear in newborns or patients with hemolytic and cardiopulmonary disorders. To assess the biological role of CECs in systemic inflammation, we studied the gene expression and function in systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells of SoJIA patients expressed upregulated erythropoiesis-related genes. It represented the largest expansion of CECs during active phase SoJIA among other inflammatory diseases. Despite the opposing roles of erythropoietin and hepcidin in erythropoiesis, both serum levels were in concert with the amounts of SoJIA-driven CECs. Circulating CECs counts in inflammatory diseases were positively correlated with the levels of C-reactive protein, IL-6, IL-18, or soluble TNF receptors. Co-culture with active SoJIA-driven CECs suppressed secretions of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top upregulated gene in SoJIA-driven CECs was ARG2 compared with CECs from cord blood controls, although cytokine production from monocytes was suppressed by co-culture, even with an arginase inhibitor. CECs are driven to the periphery during the acute phase of SoJIA at higher levels than other inflammatory diseases. Circulating CECs may control excessive inflammation via the immunoregulatory pathways, partly involving arginase-2.

scholarly journals Highly elevated serum levels of interleukin-18 in systemic juvenile idiopathic arthritis but not in other juvenile idiopathic arthritis subtypes or in Kawasaki disease: Comment on the article by Kawashima et al

2002 ◽  
Vol 46 (9) ◽  
pp. 2539-2541 ◽  
Author(s):  
Nobuaki Maeno ◽  
Syuji Takei ◽  
Yuichi Nomura ◽  
Hiroyuki Imanaka ◽  
Masashi Hokonohara ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Kawasaki Disease ◽  
Elevated Serum ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Serum Levels ◽  
Interleukin 18

scholarly journals Efficacy and Safety of Thalidomide as Adjunct Therapy in Refractory Systemic Juvenile Idiopathic Arthritis Patients

2017 ◽  
Vol 42 (1) ◽  
pp. 49-52
Author(s):  
Mohammed Mahbubul Islam ◽  
Mohammad Imnul Islam ◽  
Manik Kumar Talukdar ◽  
Mujammel Haque ◽  
Shahana A Rahman
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Permanent Disability ◽  
Systemic Jia ◽  
Conventional Dmards ◽  
Active Arthritis ◽  
Transient Elevation ◽  
Thalidomide Treatment ◽  
Systemic Onset

About 50% of systemic onset juvenile idiopathic arthritis (sJIA) patients run a recalcitrant disease course and resistant to the conventional disease modifying anti inflammatoy drugs (DMARDs), ultimately resulting in permanent disability from joint destructions. Thalidomide has been reported as an effective and safe drug in the management of systemic JIA due to its immunomodulatory properties. This was an interventional study, aimed to evaluate the efficacy of thalidomide in refractory JIA patients. Twenty five systemic JIA patients who were refractory to conventional DMARDs were included in this study. These patients were prescribed thalidomide at a dose of 2-3mg/kg/day for 12 months. Efficacy of thalidomide was assessed by using Wallace criteria at 6th month and 12th month of thalidomide treatment. Active arthritis was improved in 55% and 73% of the patients at 6th and 12th month of thalidomide treatment respectively. Fever and rash subsided in 72.8% and 81.2% of patients respectively at 12th month of follow up. Hepatosplenomegaly and lymphadenopathy regressed in 100% of patients at 12th month follow up. ESR was also improved in 50% and 68.2% cases at 6th and 12th months respectively. Few minor side effects were observed like transient elevation of liver enzyme and somnolence in this study. It may be concluded that thalidomide is safe and effective in refractory JIA patients.

Elevated circulating levels of interferon-γ and interferon-γ-induced chemokines characterise patients with macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

2016 ◽  
Vol 76 (1) ◽  
pp. 166-172 ◽  
Author(s):  
Claudia Bracaglia ◽  
Kathy de Graaf ◽  
Denise Pires Marafon ◽  
Florence Guilhot ◽  
Walter Ferlin ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Serum Levels ◽  
Interferon Γ ◽  
Mrna Levels ◽  
Circulating Levels ◽  
Activation Syndrome

ObjectivesInterferon-γ (IFNγ) is the pivotal mediator in murine models of primary haemophagocytic lymphohistiocytosis (pHLH). Given the similarities between primary and secondary HLH (sec-HLH), including macrophage activation syndrome (MAS), we investigate the involvement of the IFNγ pathway in MAS by evaluating levels of IFNγ and of the induced chemokines, and their relation with laboratory parameters of MAS in systemic juvenile idiopathic arthritis (sJIA) patients with MAS and in a murine MAS model.MethodsThe Luminex multiplexing assay was used to assess serum levels of interleukin (IL)-1β, IL-6, IFNγ and of the IFNγ-induced chemokines CXCL9, CXCL10 and CXCL11 in patients with sec-HLH (n=11) and in patients with sJIA (n=54), of whom 20 had active MAS at sampling. Expression of IFNγ-induced chemokines was assessed in IL-6 transgenic mice in which MAS is induced by TLR4 stimulation with lipopolysaccharide.ResultsLevels of IFNγ and of IFNγ-induced chemokines were markedly elevated during active MAS and sec-HLH and were significantly higher in patients with MAS compared with active sJIA without MAS. Levels in patients with active sJIA without MAS were comparable to those of patients with clinically inactive sJIA. During MAS, ferritin and alanine transferase levels and neutrophil and platelet counts were significantly correlated with serum levels of IFNγ and CXCL9. In murine MAS, serum levels of ferritin were significantly correlated with mRNA levels of Cxcl9 in liver and spleen.ConclusionsThe high levels of IFNγ and of IFNγ-induced chemokines and their correlation with the severity of laboratory abnormalities of MAS suggest a pivotal role of IFNγ in MAS.

scholarly journals AB1007 SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS: ARE DIFFERENT CLINICAL PATTERNS ASSOCIATED WITH S100A8/S100A9 SERUM LEVELS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1797.1-1797
Author(s):  
M. G. Villarreal ◽  
S. Bonaldi ◽  
L. Perez ◽  
M. Katsikas
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Serum Levels ◽  
Autoinflammatory Diseases ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Medical Visits ◽  
Clinical Patterns ◽  
Mixed Pattern

Background:Systemic juvenile idiopathic arthritis (SJIA) is a category of Juvenile Idiopathic Arthritis (JIA). Different clinical patterns (articular/systemic/both of them combined) have been recognized, possibly identifying distinct subpopulations. Serum biomarkers that reflect disease activity include S100A8/S100A9 (S100A8/9), however to date patterns of SJIA and their association with S100A8/9 has not been tested.Objectives:To evaluate S100A8/9 levels in a cohort of patients with SJIA. To determinate S100A8/9 inactive vs inactive visits. To distinguish patterns on SJIA and their association with S100A8/9. To compare serum levels of S100A8/9 with other JIA categories and autoinflammatory diseases.Methods:An unicenter, observational, cross sectional study was conduced. Patients with SJIA according ILAR whom S100A8/9 was measured as part of standard care were enrolled. Consecutive visits were included. Variables recorded were: clinical (systemic: fever, serositis, adenopathy, hepatomegaly, splenomegaly and arthritis); biochemical (S100A8/9, hemoglobin, platelet, erythrosedimentation, c-reactive protein, ferritin). Activity measures: Juvenile Arthritis Disease Activity Score (JADAS -10) and physician visual analogue scale (phy VAS).Visits were divided into active/inactive. Active visit was defined as at least one clinical feature.(systemjc and/or arthritis). Inactive visit no clinical symptoms neither JADAS-10> 1 and phy VAS: 0. SJIA patterns were defined as: “articular pattern”: those patients with arthritis without systemic features, “systemic pattern”: any systemic feature without arthritis, “mixed pattern”: both articular and systemic. Levels of S100A8/9 were tested using Calprotectin Elisa Kit. For comparisons others JIA: enthesitis related arthritis (ERA), polyarticular and autoinflammatory diseases who had at least one S100A8/9 determination were included. Descriptive statistics, Mann- Whitney U test and ANOVA were used as appropiate.Results:Forty-two patients with SJIA were included (25 F). Age at evaluation 13 (1-16.5) years. Clinical features at study baseline: arthritis 57 %, rash 19%, fever 15 %, adenopathies 6%, splenomegaly 4%, hepatomegaly 1.5%. Laboratory features (median): hemoglobin 12.2 gr/dl, platelet 314000 cel/mm3, erythrosedimentation 12.5 mm/h, c-reactive protein 0.7 mg/dl, ferritin 235 ng/ml. JADAS -10 ≥ 1: 62%. Number of active patients were 29 (69%). Scheduled Medical visits were 129 (active 65%, inactive 35%). Active visits were divided according patterns into: articular 54%, mixed 35%, systemic 11%.Serum Levels of S100A8/9 according to SJIA’ patterns.SJIAOverallActiveArticularSystemicMixedInactiveVisits129844692945S100A8/9 ng/mlMedian (range)7590(300-2625)16788(300-26250)10750(300-26250)5200(850-12250)25000(3290-2625)3103(1140-1010)S100A8/9 analysis revealed significant differences among active vs inactive medical visits (p: 0,00001). ANOVA test among SJIA`patterns showed, F:86.48, (p:0.00001). Mixed pattern was distinctive to others. S100A8/9 (medians ng/ml) in comparable diseases were: ERA: 4320, polyarticular: 4120, autoinflammatory: 6532. SJIA had the higher S100A8/9. SJIA was different than others comparable diseases (F: 11,62,p: 0.00001). Comparisons among SJIA`patternss and others disease found that systemic and articular pattern did not show differences (F.2.78, p:0.067)Conclusion:S100A8/9 was higher in SJIA compared to others diseases. It reflected disease activity. Mixed pattern evidenced to be different to others (systemic/articular). Mixed pattern was the unique that showed significative difference compared to other diseases. SJIA is probably not a single disease, but not only clinical patterns and biomarkers as S100A8/9, if not, genetic variants and their expression would be able to identify homogeneous groups towards tailored treatments.Disclosure of Interests:None declared

scholarly journals Prehospital triage of patients suffering severe dyspnoea using N-terminal pro-brain natriuretic peptide, the PreBNP trial: a randomised controlled clinical trial

2017 ◽  
Vol 7 (4) ◽  
pp. 302-310 ◽  
Author(s):  
Morten T Bøtker ◽  
Maren T Jørgensen ◽  
Carsten Stengaard ◽  
Sophie-Charlott Seidenfaden ◽  
Mona Tarpgaard ◽  
...  
Keyword(s):  
Critical Care ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Point Of Care ◽  
Routine Work ◽  
Diagnostic Work ◽  
Work Up ◽  
Critical Care Team ◽  
Diagnostic Work Up ◽  
Severe Dyspnoea

Purpose: The purpose of this study was to examine whether the addition of brain natriuretic peptide measurement to the routine diagnostic work-up by prehospital critical care team physicians improves triage in patients with severe dyspnoea. Methods: Prehospital critical care team physicians randomly assigned patients older than 18 years with severe dyspnoea to routine diagnostic work-up or diagnostic work-up with incorporated point-of-care N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement. The primary endpoint was the proportion of patients with dyspnoea of primary cardiac origin triaged directly to a department of cardiology. Results: A total of 747 patients were randomly assigned and 711 patients consented to participate, 350 were randomly assigned to the NT-proBNP group and 361 to the routine work-up group. NT-proBNP was measured in 90% (315/350) of patients in the NT-proBNP group and in 19% (70/361) of patients in the routine work-up group. There was no difference in the proportion of patients with dyspnoea of primary cardiac origin triaged directly to a department of cardiology between the NT-proBNP group and the routine work-up group (75% vs. 69%, P=0.22) in the intention-to-treat analysis. Sensitivity analysis according to the de facto diagnostics performed showed results consistent with this. No differences in hospital length of stay, intensive care unit admission rates or mortality between the NT-proBNP group and the routine work-up group were observed. Conclusion: Routine supplementary point-of-care measurement of NT-proBNP in patients with severe dyspnoea did not improve triage of patients with dyspnoea primarily caused by heart disease. ClinicalTrials.gov identifier NCT02050282.

scholarly journals Acute dyspnea in Emergency Department: point of care ultrasound in the diagnosis of atrial sarcoma

2019 ◽  
Vol 13 (1) ◽  
pp. 45-47
Author(s):  
Maria Immacolata Arnone ◽  
Giampiero Foccillo ◽  
Federica De Pisapia ◽  
Giuliano De Stefano ◽  
Giovanni Albano ◽  
...  
Keyword(s):  
Emergency Department ◽  
Point Of Care ◽  
Final Diagnosis ◽  
Point Of Care Ultrasound ◽  
Acute Dyspnea ◽  
Valve Function ◽  
Diagnostic Work ◽  
Surgery Department ◽  
Work Up ◽  
Diagnostic Work Up

We describe a rare case of a 65-year-old patient presented to Emergency Department for acute dyspnea. Traditional diagnostic work-up was done and the emergency physician promptly performed a bedside point-of-care ultrasound. A giant mass in the left atrium was detected with impairing of mitral valve function. The patient was then sent to cardiac surgery department with a final diagnosis of high-grade cardiac sarcoma.

scholarly journals The Association of Serum IL-10 Levels with the Disease Activity in Systemic-Onset Juvenile Idiopathic Arthritis Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yu Peng ◽  
Xiaohui Liu ◽  
Zhao Duan ◽  
Junkai Duan ◽  
Yulan Zhou
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Sedimentation Rate ◽  
Serum Levels ◽  
Interleukin 10 ◽  
C Reactive Protein ◽  
Clinical Marker ◽  
Reactive Protein ◽  
Erythrocyte Sedimentation ◽  
Systemic Onset

Objectives. Interleukin-10 (IL-10) has been suggested as a biomarker of disease activity in patients with adult-onset Still’s disease (AOSD). In this study, we evaluated the serum IL-10 levels and investigated its clinical relevance in systemic-onset juvenile idiopathic arthritis (SoJIA). Methods. IL-10 levels were determined in 21 patients diagnosed with SoJIA and 35 patients with fever diseases which were suspected as SoJIA, and IL-10 levels were compared between SoJIA patients with regard to disease activity, disease courses, and other biomarkers. Results. Patients with SoJIA had significantly higher levels of IL-10 compared to patients with other febrile diseases. The serum levels of IL-10 were significantly higher in active SoJIA compared to inactive and positively correlated with known disease activity markers such as erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP), ferritin (FER), and IL-6 levels. Moreover, the levels of IL-10 at diagnosis were significantly higher in SoJIA patients with a nonmonocyclic pattern than in patients with a monocyclic pattern. Compared to CRP, ESR, FER, and IL-6, IL-10 levels were superior in predicting monocyclic patients from nonmonocyclic patients. Conclusion. Compared to other febrile diseases, SoJIA patients have markedly higher levels of IL-10 which may assist with diagnosis. And a clear association of serum IL-10 levels with disease activity and disease courses in SoJIA was found. These results suggest that serum IL-10 might be a reliable clinical marker in SoJIA.

scholarly journals Follistatin-like Protein 1 and the Ferritin/Erythrocyte Sedimentation Rate Ratio Are Potential Biomarkers for Dysregulated Gene Expression and Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis

2013 ◽  
Vol 40 (7) ◽  
pp. 1191-1199 ◽  
Author(s):  
Mark Gorelik ◽  
Ndate Fall ◽  
Mekibib Altaye ◽  
Michael G. Barnes ◽  
Susan D. Thompson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Juvenile Idiopathic Arthritis ◽  
Sedimentation Rate ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Serum Levels ◽  
Erythrocyte Sedimentation ◽  
Activation Syndrome ◽  
New Onset

Objective.Follistatin-like protein 1 (FSTL-1) is a secreted glycoprotein overexpressed in certain inflammatory diseases. Our objective was to correlate FSTL-1 levels with gene expression, known biomarkers, and measures of disease activity in systemic juvenile idiopathic arthritis (sJIA), including macrophage activation syndrome (MAS).Methods.FSTL-1 serum levels were measured by ELISA in 28 patients with sJIA, including 7 patients who developed MAS, and 30 healthy controls. Levels were correlated with erythrocyte sedimentation rate (ESR), ferritin, and soluble interleukin-2 receptor-α (sIL-2Rα). Gene expression based on FSTL-1 levels was analyzed in peripheral blood mononuclear cells (PBMC).Results.Serum levels of FSTL-1 were elevated at time of presentation of sJIA (mean 200.7 ng/ml) and decreased to normal (mean 133.7 ng/ml) over 24 months (p < 0.01). FSTL-1 levels were markedly elevated during acute MAS (mean 279.8 ng/ml) and decreased to normal following treatment (p < 0.001). FSTL-1 levels correlated with serum markers of inflammation, including sIL-2Rα and ferritin. Ferritin/ESR ratio was superior to ferritin, sIL-2Rα, and FSTL-1 in discriminating MAS from new-onset sJIA. PBMC from patients with FSTL-1 levels > 200 ng/ml showed altered expression of genes related to innate immunity, erythropoiesis, and natural killer cell dysfunction. Two patients with the highest FSTL-1 levels at disease onset (> 300 ng/ml) ultimately developed MAS.Conclusion.Elevated pretreatment serum FSTL-1 levels in sJIA are associated with dysregulated gene expression suggestive of occult MAS, and may have utility in predicting progression to overt MAS. Ferritin/ESR ratio may be superior to ferritin alone in discriminating overt MAS from new-onset sJIA.

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