scholarly journals Immunoprofiling of active and inactive systemic juvenile idiopathic arthritis reveals distinct biomarkers: a single-center study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heshuang Qu ◽  
Erik Sundberg ◽  
Cecilia Aulin ◽  
Manoj Neog ◽  
Karin Palmblad ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Inflammatory Diseases ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
High Mobility ◽  
Healthy Controls ◽  
Cellular Functions ◽  
Cross Sectional ◽  
Immune Mechanisms ◽  
Molecular Pattern ◽  
Canonical Pathways

Abstract Background This study aimed to perform an immunoprofiling of systemic juvenile idiopathic arthritis (sJIA) in order to define biomarkers of clinical use as well as reveal new immune mechanisms. Methods Immunoprofiling of plasma samples from a clinically well-described cohort consisting of 21 sJIA patients as well as 60 age and sex matched healthy controls, was performed by a highly sensitive proteomic immunoassay. Based on the biomarkers being significantly up- or down-regulated in cross-sectional and paired analysis, related canonical pathways and cellular functions were explored by Ingenuity Pathway Analysis (IPA). Results The well-studied sJIA biomarkers, IL6, IL18 and S100A12, were confirmed to be increased during active sJIA as compared to healthy controls. IL18 was the only factor found to be increased during inactive sJIA as compared to healthy controls. Novel factors, including CASP8, CCL23, CD6, CXCL1, CXCL11, CXCL5, EIF4EBP1, KITLG, MMP1, OSM, SIRT2, SULT1A1 and TNFSF11, were found to be differentially expressed in active and/or inactive sJIA and healthy controls. No significant pathway activation could be predicted based on the limited factor input to the IPA. High Mobility Group Box 1 (HMGB1), a damage associated molecular pattern being involved in a series of inflammatory diseases, was determined to be higher in active sJIA than inactive sJIA. Conclusions We could identify a novel set of biomarkers distinguishing active sJIA from inactive sJIA or healthy controls. Our findings enable a better understanding of the immune mechanisms active in sJIA and aid the development of future diagnostic and therapeutic strategies.

scholarly journals A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis

2017 ◽  
Vol 214 (11) ◽  
pp. 3449-3466 ◽  
Author(s):  
Alma-Martina Cepika ◽  
Romain Banchereau ◽  
Elodie Segura ◽  
Marina Ohouo ◽  
Brandi Cantarel ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Inflammatory Diseases ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Unknown Etiology ◽  
Integrated Analysis ◽  
Cell Phenotype ◽  
Protein Levels ◽  
Aryl Hydrocarbon ◽  
Immune Alterations

The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During disease remission and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8, and TLR7 stimulation. Isolated sJIA monocytes underexpressed the IL-1 inhibitor aryl hydrocarbon receptor (AHR) at baseline and accumulated higher levels of intracellular IL-1β after stimulation. Supporting the demonstration that AHR down-regulation skews monocytes toward macrophage differentiation, sJIA monocytes differentiated in vitro toward macrophages, away from the dendritic cell phenotype. This might contribute to the increased incidence of macrophage activation syndrome in these patients. Integrated analysis of high-dimensional data can thus unravel immune alterations predisposing to complex inflammatory diseases.

scholarly journals Prevalence of Temporomandibular Disorder in children and adolescents with Juvenile Idiopathic Arthritis – a Norwegian cross sectional multicenter study

2020 ◽  
Author(s):  
Johannes Fischer ◽  
Marit Slåttelid Skeie ◽  
Karen Rosendahl ◽  
Karin Tylleskär ◽  
Stein Atle Lie ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Children And Adolescents ◽  
Multicenter Study ◽  
Temporomandibular Disorder ◽  
Clinical Signs ◽  
Masticatory Muscles ◽  
Health Examination ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Jaw Movement

Abstract Background. Children and adolescents with JIA may suffer pain from temporomandibular disorder (TMD) and routines for the assessment of temporomandibular joint (TMJ) pain for the health and dental care are lacking. The aims were to examine the prevalence of TMD in children and adolescents with juvenile idiopathic arthritis (JIA) as compared to their healthy peers and to examine potential associations between JIA and TMD.Methods. This comparative cross-sectional study is part of a longitudinal multicenter study performed during 2015 - 2020, including 228 children and adolescents aged 4-16 years, with a diagnosis of JIA according to the ILAR criteria. This sub-study draws on a subset of data from the first study visit, including assessments of TMD as part of a broader oral health examination. Participants with JIA were matched with healthy controls according to gender, age, and center site. Calibrated examiners performed the clinical oral examinations according to a standardized protocol, including shortened versions of diagnostic criteria for TMD (DC/TMD) and the former EuroTMJoint Recommendations for Clinical TMJ Assessment in Patients Diagnosed with JIA. Symptoms were recorded and followed by a clinical examination assessing the masticatory muscles and TMJ`s.Results. In our cohort of 221 participants with JIA and corresponding controls, 88 participants with JIA (39.8%) and 25 (11.3%) controls revealed TMD based on symptoms and clinical signs. Painful TMD during the last 30 days was reported in 59 (26.7%) participants with JIA vs. 10 (5.0%) of the healthy controls (p<0.001). Vertical unassisted jaw movement was lower in JIA than in controls; mean 46.2 mm vs. 49.0 mm, respectively (p <0.001). Among participants with JIA, a higher proportion of those using synthetic disease-modifying antirheumatic-drugs (sDMARDs) and biologic (bDMARDs) presented with painful masticatory muscle and TMJs at palpation.Conclusion. Symptoms or clinical signs of TMD were seen in approximately half of the JIA patients compared to about one fourth of their healthy peers. Painful palpation to masticatory muscles and decreased vertical unassisted jaw movement were more frequent in participants with JIA than among healthy controls and should be part of both medical and dental routine examinations in JIA.

scholarly journals Association between high mobility group box 1 protein and juvenile idiopathic arthritis: a prospective longitudinal study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Xu ◽  
Yu Zhang ◽  
Zhi-Yong Zhang ◽  
Xue-Mei Tang
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Longitudinal Study ◽  
High Mobility ◽  
Healthy Controls ◽  
C Reactive Protein ◽  
Prospective Longitudinal Study ◽  
Reactive Protein ◽  
Systemic Jia ◽  
Duration Of Disease ◽  
Prospective Longitudinal

Abstract Objective To analyze the levels of high mobility group box 1 (HMGB1) protein on different courses of juvenile idiopathic arthritis (JIA). Methods In our prospective longitudinal study, children with JIA were included with their blood samples collected at the first visit, 1-month, 3-month, and 6-month follow-up, respectively. Samples were also collected from healthy controls and children with reactive arthritis at the first visit. Levels of HMGB1 were determined using enzyme-linked immunosorbent assays. Clinical disease characteristics and routine laboratory findings were analyzed as well. Results A total of 64 children were enrolled, of whom 31 (48.4%) were female. The median age at the first visit for participants with JIA was 9.25 years (range, 1.42–15.42) and the median duration of disease was 2.38 months (range, 1.53–49.31). Serum HMGB1 levels at the first visit were significantly elevated in children with systemic JIA compared with other groups, and so were in enthesitis-related arthritis versus healthy controls. Significant correlations were established at the first visit between HMGB1 levels and duration of disease, C-reactive protein, percentage of neutrophils, and ferritin. Data from all samples revealed that serum HMGB1 levels in JIA were significantly associated with erythrocyte sedimentation rates, C-reactive protein, percentage of neutrophils, and disease activity scores. Conclusions Serum HMGB1 may be associated with clinical disease activity of JIA and specifically increased at the first visit in children with systemic JIA, suggesting its function as a sensitive inflammatory marker. Further large-scale studies are warranted to explore its spectrum in JIA.

scholarly journals Prevalence of temporomandibular disorder in children and adolescents with juvenile idiopathic arthritis – a Norwegian cross- sectional multicentre study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
J. Fischer ◽  
M. S. Skeie ◽  
K. Rosendahl ◽  
K. Tylleskär ◽  
S. Lie ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Children And Adolescents ◽  
Temporomandibular Disorder ◽  
Clinical Signs ◽  
Masticatory Muscles ◽  
Healthy Controls ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Cross Sectional ◽  
Disease Modifying

Abstract Background Children and adolescents with juvenile idiopathic arthritis (JIA) may suffer pain from temporomandibular disorder (TMD). Still, routines for the assessment of temporomandibular joint (TMJ) pain in health and dental care are lacking. The aims of this study were to examine the prevalence of TMD in children and adolescents with JIA compared to their healthy peers and to investigate potential associations between JIA and TMD. Methods This comparative cross-sectional study is part of a longitudinal multicentre study performed during 2015–2020, including 228 children and adolescents aged 4–16 years with a diagnosis of JIA according to the ILAR criteria. This particular substudy draws on a subset of data from the first study visit, including assessments of TMD as part of a broader oral health examination. Children and adolescents with JIA were matched with healthy controls according to gender, age, and centre site. Five calibrated examiners performed the clinical oral examinations according to a standardised protocol, including shortened versions of the diagnostic criteria for TMD (DC/TMD) and the TMJaw Recommendations for Clinical TMJ Assessment in Patients Diagnosed with JIA. Symptoms were recorded and followed by a clinical examination assessing the masticatory muscles and TMJs. Results In our cohort of 221 participants with JIA and 221 healthy controls, 88 (39.8%) participants with JIA and 25 (11.3%) healthy controls presented with TMD based on symptoms and clinical signs. Painful TMD during the last 30 days was reported in 59 (26.7%) participants with JIA vs. 10 (5.0%) of the healthy controls (p <  0.001). Vertical unassisted jaw movement was lower in participants with JIA than in controls, with means of 46.2 mm vs. 49.0 mm, respectively (p <  0.001). Among participants with JIA, a higher proportion of those using synthetic disease-modifying antirheumatic-drugs and biologic disease-modifying antirheumatic-drugs presented with painful masticatory muscles and TMJs at palpation. Conclusion Symptoms and clinical signs of TMD were seen in approximately half of the JIA patients compared to about one fourth of their healthy peers. Painful palpation to masticatory muscles and decreased vertical unassisted jaw movement were more frequent in participants with JIA than among healthy controls and should be part of both medical and dental routine examinations in patients with JIA.

scholarly journals Idiopathic Pulmonary Hemosiderosis in a Child with Recurrent Macrophage Activation Syndrome Secondary to Systemic Juvenile Idiopathic Arthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Kenan Barut ◽  
Sezgin Sahin ◽  
Amra Adrovic ◽  
Velat Sen ◽  
Ozgur Kasapcopur
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Inflammatory Diseases ◽  
Delayed Diagnosis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Pulmonary Hemosiderosis ◽  
Pulmonary Manifestations ◽  
Life Threatening ◽  
Activation Syndrome

Macrophage activation syndrome, a severe complication of systemic juvenile idiopathic arthritis and other inflammatory diseases, represents one of the most important rheumatological emergencies. Delayed diagnosis could lead to life-threatening complications. Pulmonary hemosiderosis has been classically characterized by a triad of anemia, hemoptysis, and lung infiltrates on chest radiogram. Although the majority of patients of pulmonary hemosiderosis are considered idiopathic, secondary hemosiderosis associated with known diseases could be seen. In this case report, we aimed to present gradually increased pulmonary manifestations due to pulmonary hemosiderosis with recurrent macrophage activation syndrome attacks in a child with systemic juvenile idiopathic arthritis.

scholarly journals Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

2020 ◽  
Author(s):  
Guillermo Barturen ◽  
Sepideh Babaei ◽  
Francesc Català-Moll ◽  
Manuel Martínez-Bueno ◽  
Zuzanna Makowska ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Healthy Controls ◽  
Inception Cohort ◽  
Cluster Assignment ◽  
Systemic Autoimmune Diseases ◽  
Cross Sectional ◽  
Molecular Stratification ◽  
Molecular Pattern ◽  
Clinical Diagnoses ◽  
Molecular Patterns

SUMMARYBackgroundClinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification.MethodsWith the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. In addition, an inception cohort was prospectively followed for 6 and 14 months to validate the results and analyze if cluster assignment changed or not with time.ResultsFour clusters were identified. Three clusters were aberrant, representing ‘inflammatory’, ‘lymphoid’, and ‘interferon’ patterns each including all diagnoses and defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern and accumulated also healthy controls. An independent inception cohort showed that with time, the molecular clusters remain stable, showing that single aberrant molecular signatures characterize each individual patient.ConclusionsPatients with SADs can be jointly stratified into three stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of therapy non-responsiveness marking a paradigm shift in the view of SADs.

scholarly journals Kawasaki Disease and Systemic Juvenile Idiopathic Arthritis – Two Ends of the Same Spectrum

2021 ◽  
Vol 9 ◽  
Author(s):  
Ellen Go ◽  
Mira van Veenendaal ◽  
Cedric Manlhiot ◽  
Rayfel Schneider ◽  
Brian W. McCrindle ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Coronary Artery ◽  
Kawasaki Disease ◽  
Macrophage Activation ◽  
Inflammatory Diseases ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Treatment Regimens ◽  
Coronary Artery Dilatation ◽  
High Prevalence ◽  
Disease Entities

Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (sJIA) are two distinct systemic inflammatory diseases of childhood. Each diagnosis is based on criteria, but numerous clinical features are overlapping. As no specific diagnostic tests are available, differentiation between both disease entities can be challenging. Here, we describe the disease course of patients with co-diagnosis of both KD and sJIA (KD/sJIA). All our KD (n = 1765) and sJIA (n = 112) cases were critically reviewed for co-diagnosis of KD/sJIA. Eight KD/sJIA cases were identified and their clinical presentation, treatment regimens, coronary artery outcome and complications are herein described. Each KD/sJIA patient fulfilled diagnostic criteria for KD and for sJIA. Ongoing fever, rash and arthritis were present in each patient. The KD/sJIA patients had recalcitrant KD requiring multiple doses of intravenous immunoglobulin and steroids. Five patients had coronary artery dilatation at KD diagnosis, which resolved in all by 6 weeks. Pericardial effusion was present in 5 patients. One KD/sJIA patient developed macrophage activation syndrome. In conclusion, a small proportion (0.5%) of our KD patients evolved into sJIA, and 7% of our sJIA population presented initially as KD. KD/sJIA patients were characterized by a recalcitrant KD course and a high prevalence of coronary artery dilatation. Patients with co-diagnoses may provide a clue to potentially shared immunopathology in KD and sJIA, leading us to posit that both entities may be part of the same clinical spectrum.

scholarly journals Serum HMGB1 Serves as a Novel Laboratory Indicator Reflecting Disease Activity and Treatment Response in Ankylosing Spondylitis Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Chenqiong Wang ◽  
Ye Miao ◽  
Xuefen Wu ◽  
Yishu Huang ◽  
Mengchen Sun ◽  
...  
Keyword(s):  
Disease Activity ◽  
Inflammatory Diseases ◽  
High Mobility ◽  
Serum Levels ◽  
Inflammatory Factor ◽  
Healthy Controls ◽  
Hip Joints ◽  
Significant Difference ◽  
Autoimmune And Inflammatory Diseases

Objective. High mobility group box 1 (HMGB1) is a late inflammatory factor participating in the pathogenesis of various autoimmune and inflammatory diseases. In the current study, we analyzed the association between serum levels of HMGB1 and clinical features of AS patients before and during treatment.Methods. Serum HMGB1 was detected in 147 AS patients and 61 healthy controls using ELISA. We evaluated the association between HMGB1 and extra-articular manifestations as well as disease severity indices. Among these AS patients, 41 patients received close follow-up at 1, 3, and 6 months after treatment. This group comprised 25 patients treated with anti-TNF-αbiologics and 16 patients receiving oral NSAIDs plus sulfasalazine.Results. The serum HMGB1 of AS patients was significantly higher than in healthy controls and positively correlated with BASDAI, BASFI, ASDAS-ESR, ASDAS-CRP, ESR, and CRP, but not with HLA-B27, anterior uveitis, and recurrent diarrhea. There was no significant difference between patients with radiographic damage of hip joints and those without. We observed that serum HMGB1 paralleled disease activity after treatment.Conclusion. Serum level of HMGB1 is higher in AS patients, and to some extent, HMGB1 can reflect the activity of AS and be used as a laboratory indicator to reflect the therapeutic response.

scholarly journals Neurons Are a Primary Driver of Inflammation Via Release of HMGB1

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2791
Author(s):  
Huan Yang ◽  
Ulf Andersson ◽  
Michael Brines
Keyword(s):  
Molecular Markers ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
High Mobility ◽  
Sensory Nerves ◽  
Knock Out ◽  
Etiologic Role ◽  
Molecular Pattern ◽  
Primary Driver ◽  
Direct Targeting

Recent data show that activation of nociceptive (sensory) nerves turns on localized inflammation within the innervated area in a retrograde manner (antidromically), even in the absence of tissue injury or molecular markers of foreign invaders. This neuroinflammatory process is activated and sustained by the release of neuronal products, such as neuropeptides, with the subsequent amplification via recruitment of immunocompetent cells, including macrophages and lymphocytes. High mobility group box 1 protein (HMGB1) is a highly conserved, well characterized damage-associated molecular pattern molecule expressed by many cells, including nociceptors and is a marker of inflammatory diseases. In this review, we summarize recent evidence showing that neuronal HMGB1 is required for the development of neuroinflammation, as knock out limited to neurons or its neutralization via antibodies ameliorate injury in models of nerve injury and of arthritis. Further, the results of study show that HMGB1 is actively released during neuronal depolarization and thus plays a previously unrecognized key etiologic role in the initiation and amplification of neuroinflammation. Direct targeting of HMGB1 is a promising approach for novel anti-inflammatory therapy.

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