High mobility group box protein 1—A prognostic marker for structural joint damage in 10-year follow-up of patients with juvenile idiopathic arthritis

Pullerits, Rille; Schierbeck, Hanna; Uibo, Karin; Liivamägi, Hille; Tarraste, Sirje; Talvik, Tiina; Sundberg, Erik; Pruunsild, Chris

doi:10.1016/j.semarthrit.2016.08.017

Cited by 10 publications

(5 citation statements)

References 27 publications

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“…Such biomarkers would be helpful in monitoring therapy response, progression of joint damage and potentially predicting disease outcome. Previously the biomarker research in JIA focused on different antibodies: RF, anti-nuclear antibodies and anticitrullinated protein antibodies (ACPA) and on inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein, cytokines and alarmins (10)(11)(12)(13)(14)(15)(16). The prognostic value of these are not comprehensive, there are indications that inflammatory markers may predict erosion (11) and that ACPAs may help to sub-diagnose JIA patients with bone involvement and erosions although with low sensitivity (15).…”

Section: Introductionmentioning

confidence: 99%

Juvenile idiopathic arthritis patients have a distinct cartilage and bone biomarker profile that differs from healthy and knee-injured children

Struglics

Saleh

Sundberg

et al. 2020

Clinical and Experimental Rheumatology

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ObjectiveJoint destruction is a hallmark of juvenile idiopathic arthritis (JIA). Clinical evaluation and radiographic imaging are current methods to identify destruction. Biomarkers could aid an earlier and more sensitive diagnosis. Our aim was to investigate levels of bone and cartilage degradation biomarkers in JIA patients, compared to healthy children or juveniles with knee injuries. Methods Triple-paired synovial fluid, plasma and urine samples from 29 JIA patients were compared to 61 plasma samples from healthy children and synovial fluid from 41 knee-injured juveniles. Cartilage biomarkers ARGS neoepitope of aggrecan (ARGS), cartilage oligomeric matrix protein (COMP), type II collagen epitope (C2C), bone biomarkers N-terminal type Icollagen cross-linked telopeptide (NTX-I) and tartrate-resistant acid phosphatase 5b (TRAP5b) were analysed by immunoassays. Results Plasma levels of ARGS, C2C, COMP and TRAP5bwere increased in JIA compared to healthy children. Compared to knee-injured juveniles, synovial fluid C2C and TRAP5b were increased in JIA, while ARGS and COMP were decreased. For JIA patients, local (synovial fluid) and systemic (plasma/urine) levels of bone biomarkers correlated positively; age correlated negatively to plasma levels of C2C and TRAP5b; no correlation was found between biomarkers and gender, affected joint count, disease duration or medication. Conclusion Elevated levels of destruction biomarkers in JIA compared to healthy children indicate a potential to serve as clinicaltools for destructive joint disease. High levels of TRAP5b, NTX-I and collagen II in JIA in contrast to more pronounced aggrecan and COMP degradation in juvenile knee injuries, suggests that JIA patients have a unique biomarker pattern, different from healthy and knee-injured children.

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Section: Introductionmentioning

confidence: 99%

Juvenile idiopathic arthritis patients have a distinct cartilage and bone biomarker profile that differs from healthy and knee-injured children

Struglics

Saleh

Sundberg

et al. 2020

Clinical and Experimental Rheumatology

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“…Moreover, HMGB1 was related to the disease activity scores, especially sJADAS, based on the analysis of all samples from children with JIA, which indicated a specific marker for disease activity in JIA. Previous studies have demonstrated that HMGB1 levels were related to destructive JIA and more sensitive than CRP in detecting hepatosplenomegaly or serositis among patients with systemic JIA [ 14 , 25 ]. Schierbeck et al [ 13 ] found that HMGB1 in synovial fluid was the highest in patients with early disease onset irrespective of disease duration.…”

Section: Discussionmentioning

confidence: 99%

“…For children with JIA, females are more likely to be positive for anti-nuclear antibodies and HMGB1 antibodies [ 12 ]. It has been shown that HMGB1 levels were associated with inflammatory activity, early-onset, disease progression, and long-term prognosis in children with JIA [ 13 , 14 ]. Reactive arthritis (ReA) refers to acute self-limited aseptic arthritis related to previous extra-articular infection that can follow streptococcal infection and genitourinary or/and gastrointestinal infection, which occasionally shares a similar clinical presentation with JIA.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

et al. 2021

Pediatr Rheumatol

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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.

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“…The patient group comprised 131 Estonian children diagnosed with JIA during the population-based prevalence and incidence studies in the Children's Clinic, Tartu University Hospital and Tallinn Children's Hospital during 1995–2000 [16–18]. The inclusion criteria to the study were as follows: children under the age of 16 years who had (a) arthritis of unknown cause in at least one joint for at least 6 weeks or (b) inflammatory back pain and enthesitis, or (c) spiking fever together with other symptoms suggestive of systemic arthritis.…”

Section: Methodsmentioning

confidence: 99%

Low Serum IGF-1 in Boys with Recent Onset of Juvenile Idiopathic Arthritis

Lundell

Erlandsson

Bokarewa

et al. 2018

Journal of Immunology Research

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Background Liver-derived insulin-like growth factor-1 (IGF-1) contributes bone formation. Decreased IGF-1 levels are common in juvenile idiopathic arthritis (JIA), but whether IGF-1 is related to sex and differ during the pathogenic progress of JIA is unknown. Objective The aim of this study was to examine IGF-1 levels in boys and girls with newly diagnosed JIA, with established JIA and in controls. Methods The study group included 131 patients from the Estonian population-based prevalence JIA study. Blood samples were obtained from 27 boys and 38 girls with early JIA (≤1 month from the diagnosis), 29 boys and 36 girls with established JIA (mean disease duration 18 months), and from 47 age- and sex-matched controls. Results IGF-1 levels in boys were significantly decreased in early JIA compared to male controls, while IGF-1 levels in girls were comparable between JIA and controls. In early JIA, IGF-1 levels were 12-fold lower in boys relative to girls. In controls, IGF-1 levels correlated with both age and height, while these correlations were lost in boys with early JIA. Conclusion We report a sex-dependent deficiency in serum IGF-1 in boys with early JIA, which argues for sex-related differences in biological mechanisms involved in the disease pathogenesis.

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High mobility group box protein 1—A prognostic marker for structural joint damage in 10-year follow-up of patients with juvenile idiopathic arthritis

Cited by 10 publications

References 27 publications

Juvenile idiopathic arthritis patients have a distinct cartilage and bone biomarker profile that differs from healthy and knee-injured children

Juvenile idiopathic arthritis patients have a distinct cartilage and bone biomarker profile that differs from healthy and knee-injured children

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

Low Serum IGF-1 in Boys with Recent Onset of Juvenile Idiopathic Arthritis

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