| 1. |
- Glerup, Mia, et al.
(författare)
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Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort
- 2024
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Ingår i: RMD OPEN. - 2056-5933. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting.Methods Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables.Results Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1 beta (IL-1 beta), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset.Conclusion Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.
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| 2. |
- Alberdi-Saugstrup, Mikel, et al.
(författare)
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High-sensitive CRP as a predictive marker of long-term outcome in juvenile idiopathic arthritis
- 2017
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Ingår i: Rheumatology International. - : SPRINGER HEIDELBERG. - 0172-8172 .- 1437-160X. ; 37:5, s. 695-703
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate whether C-reactive protein (CRP), including variation within the normal range, is predictive of long-term disease outcome in Juvenile Idiopathic Arthritis (JIA). Consecutive patients with newly diagnosed JIA were included prospectively from defined geographic areas of the Nordic countries from 1997 to 2000. Inclusion criteria were availability of a baseline serum sample within 12 months after disease onset and 8-year clinical assessment data. Systemic onset JIA was not included. CRP was measured by high-sensitive ELISA (detection limit of 0.2 mg/l). One hundred and thirty participants with a median follow-up time of 97 months (range 95-100) were included. At follow-up, 38% of the patients were in remission off medication. Absence of remission was associated with elevated level of CRP at baseline (odds ratio (OR) 1.33, confidence interval (CI) 1.08-1.63, p = 0.007). By applying a cutoff at the normal upper limit (> 10 mg/l), the risk of not achieving remission was increased to an OR of 8.60 (CI 2.98-24.81, p < 0.001). Variations of CRP within the normal range had no predictive impact on disease activity at follow-up. Baseline levels of ESR were available in 80 patients (61%) and elevated ESR was associated with absence of remission in a multivariable logistic regression analysis (OR 2.32, CI 1.35-4.00, p = 0.002). This results of this study indicate that baseline CRP concentrations above 10 mg/l are predictive of a poor outcome at 8-year follow-up. We could not demonstrate any predictive value of CRP variations within the normal range.
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| 3. |
- Arnstad, Ellen Dalen, et al.
(författare)
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Early Self-Reported Pain in Juvenile Idiopathic Arthritis as Related to Long-Term Outcomes : Results From the Nordic Juvenile Idiopathic Arthritis Cohort Study
- 2019
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Ingår i: Arthritis care & research. - : WILEY. - 2151-464X .- 2151-4658. ; 71:7, s. 961-969
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Tidskriftsartikel (refereegranskat)abstract
- Objective To study self-reported pain early in the disease course of juvenile idiopathic arthritis (JIA) as a predictor of long-term disease outcomes. Methods Consecutive cases of JIA with disease onset from 1997 to 2000 from defined geographical areas of Norway, Sweden, Finland, and Denmark were prospectively enrolled in this population-based cohort study. Self-reported, disease-related pain was measured on a 10-cm visual analog scale (VAS pain). Inclusion criteria were a baseline visit with a pain score 6 months after disease onset, followed by an 8-year study visit. Remission was defined according to Wallace et al (2004) preliminary criteria. Functional disability was measured by the Childhood Health Assessment Questionnaire and the Child Health Questionnaire Parent Form if the child was age <18 years and by the Health Assessment Questionnaire if age >= 18 years. Damage was scored using the Juvenile Arthritis Damage Index. Results The final study cohort consisted of 243 participants, and 120 participants (49%) had oligoarticular onset. At baseline, 76% reported a VAS pain score >0 compared to 57% reporting at 8 years. Half of those who reported baseline pain also reported pain at 8 years but at a lower intensity. Compared to no pain, higher pain intensity at baseline predicted more pain at 8 years, more functional disability, more damage, and less remission without medication. Baseline pain predicted more use of disease-modifying antirheumatic drugs/biologics during the disease course. Participants with oligoarticular JIA reporting pain at baseline were more likely to develop extended oligoarticular JIA or other JIA categories with an unfavorable prognosis. Conclusion Early self-reported, disease-related pain among children and adolescents with JIA is common and seems to predict persistent pain and unfavorable long-term disease outcomes.
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| 4. |
- Arnstad, Ellen Dalen, et al.
(författare)
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Fatigue in young adults with juvenile idiopathic arthritis 18 years after disease onset : data from the prospective Nordic JIA cohort
- 2021
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Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background To study fatigue in young adults with juvenile idiopathic arthritis (JIA) 18 years after disease onset, and to compare with controls. Methods Consecutive children with onset of JIA between 1997 and 2000, from geographically defined areas of Norway, Sweden, Denmark and Finland were followed for 18 years in a close to population-based prospective cohort study. Clinical features, demographic and patient-reported data were collected. Inclusion criteria in the present study were a baseline visit 6 months after disease onset, followed by an 18-year follow-up with available self-reported fatigue score (Fatigue Severity Scale (FSS), 1-7). Severe fatigue was defined as FSS >= 4. For comparison, Norwegian age and sex matched controls were used. Results Among 377 young adults with JIA, 26% reported severe fatigue, compared to 12% among controls. We found higher burden of fatigue among participants with sleep problems, pain, poor health, reduced participation in school/work, physical disability, active disease, or use of disease-modifying anti-rheumatic drugs (DMARDs)/biologics/systemic steroids. In contrast, participants without these challenges, had fatigue scores similar to controls. Active disease assessed at all three time points (baseline, 8-year and 18-year follow-up) was associated with higher mean fatigue score and higher percentage of severe fatigue compared to disease courses characterized by periods of inactive disease. Predictors of fatigue at the 18-year follow-up were female sex and diagnostic delay of >= 6 months at baseline, and also pain, self-reported poor health, active disease, and previous/ongoing use of DMARDs/biologics at 8 years. Conclusions Fatigue is a prominent symptom in young adults with JIA, with higher fatigue burden among participants with poor sleep, pain, self-reported health problems, active disease, or use of DMARDs/biologics. Participants without these challenges have results similar to controls. Patient- and physician-reported variables at baseline and during disease course predicted fatigue at 18-year follow-up.
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| 5. |
- Berntson, Lillemor, et al.
(författare)
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Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)
- 2014
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Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 12, s. 22-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods: The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results: Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions: Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied.
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| 7. |
- Brix, Ninna, et al.
(författare)
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Inflammatory Biomarkers Can Differentiate ALL with Arthropathy from JIA Better Than Standard Blood Tests.
- 2023
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Ingår i: The Journal of pediatrics. - 1097-6833. ; 258
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA).In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n=150, including 27 with arthropathy) and JIA (n=236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age.In ALL, the levels of S100A9, S100A12, IL-1 beta, IL-4, IL-13, IL-17, MMP-3, and MPO were low compared with JIA (p <0.001). IL-13 had an AUC of 100% (95% CI 100-100%) due to no overlap between the serum levels in the two groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97-100%) and 98% (95% CI 94-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate.The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA.
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| 8. |
- Brix, Ninna, et al.
(författare)
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M-ficolin: a valuable biomarker to identify leukaemia from juvenile idiopathic arthritis.
- 2022
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Ingår i: Archives of disease in childhood. - : BMJ. - 1468-2044 .- 0003-9888. ; 107:4, s. 371-376
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Tidskriftsartikel (refereegranskat)abstract
- Distinction on clinical grounds between acute lymphoblastic leukaemia presenting with arthropathy (ALLarthropathy) and juvenile idiopathic arthritis (JIA) is difficult, as the clinical and paraclinical signs of leukaemia may be vague. The primary aim was to examine the use of lectin complement pathway proteins as markers to differentiate ALLarthropathy from JIA. The secondary aims were to compare the protein levels at baseline and follow-up in a paired number of children with ALL and to examine the correlation with haematology counts, erythrocyte sedimentation reaction (ESR), C-reactive protein (CRP), blasts, relapse and death.In this observational study, we measured M-ficolin, CL-K1 and MASP-3 in serum from children with ALL (n=151) and JIA (n=238) by time-resolved immunofluorometric assays. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated '10-fold cross-validation' with 100 repetitions computing the area under the curve (AUC) as well as positive and negative predictive values in order to evaluate the predictive performance.The level of M-ficolin was higher in JIA than ALLtotal and the ALLarthropathy subgroup. The M-ficolin level normalised after remission of ALL. M-ficolin could differentiate ALL from JIA with an AUC of 94% and positive predictive value (PPV) of 95%, exceeding CRP and haemoglobin. In a dichotomised predictive model with optimal cut-offs for M-ficolin, platelets and haemoglobin, AUC was 99% and PPV 98% in detecting ALL from JIA.M-ficolin is a valuable marker to differentiate the child with ALL from JIA.
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| 9. |
- Ekelund, Maria, et al.
(författare)
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Psoriasis and associated variables in classification and outcome of juvenile idiopathic arthritis - an eight-year follow-up study
- 2017
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Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: To study the impact of psoriasis and features associated with psoriasis on classification and outcome in a population-based follow-up cohort of children with juvenile idiopathic arthritis (JIA). Methods: In all, 440 children with JIA were followed for a median of 8 years in a prospective Nordic population-based cohort study. Data for remission was available for 427 of these children. The presence of psoriasis, psoriasis-like rash, dactylitis, nail pitting, enthesitis, tenosynovitis and heredity was assessed in relation to ILAR classification and remission. Results: Clinical findings associated with psoriasis developed consecutively during the 8-year period. Six of 14 children with psoriasis were not classified as juvenile psoriatic arthritis according to the ILAR criteria at 8 year follow-up. Dactylitis was more common in children with early onset of JIA. After 8 years we found a cumulative median number of eleven arthritic joints in children with psoriasis or psoriasis- like rash compared with six in the rest of the cohort (p = 0.02). Also, the chance for not being in remission after 8 years increased significantly in patients with psoriasis, psoriasis-like rash or at least two of: 1) first-degree heredity for psoriasis or psoriatic arthritis, 2) dactylitis or 3) nail pitting, compared with the rest of the group (OR 3.32, p = 0.010). Conclusions: Our results indicate a more severe disease over time in psoriasis- associated JIA, as features of psoriasis develop during the disease course. This group is a major challenge to encompass in a future JIA classification in order to facilitate early tailored treatment.
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| 10. |
- Foell, Dirk, et al.
(författare)
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A novel serum calprotectin (MRP8/14) particle-enhanced immuno-turbidimetric assay (sCAL turbo) helps to differentiate systemic juvenile idiopathic arthritis from other diseases in routine clinical laboratory settings
- 2023
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Ingår i: Molecular and Cellular Pediatrics. - : Springer. - 2194-7791. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings.Methods: To evaluate the accuracy in identifying children with SJIA, the performance of a particle-enhanced immuno-turbidimetric assay for serum calprotectin (sCAL turbo) on an automated laboratory instrument was analyzed. Samples from 615 children were available with the diagnoses SJIA (n = 99), non-systemic JIA (n = 169), infections (n = 51), other inflammatory diseases (n = 126), and acute lymphoblastic leukemia (ALL, n = 147). In addition, samples from 23 healthy controls were included.Results: The sCAL turbo assay correlated well with the MRP8/14 ELISA used in previous validation studies (r = 0.99, p < 0.001). It could reliably differentiate SJIA from all other diagnoses with significant accuracy (cutoff at 10,500 ng/ml, sensitivity 84%, specificity 94%, ROC area under curve 0.960, p < 0.001).Conclusions: Serum calprotectin analyses are a helpful tool supporting the diagnosis of SJIA in children with prolonged fever or inflammatory disease. Here, we show that an immuno-turbidimetric assay for detection of serum calprotectin on an automated laboratory instrument can be implemented in clinical laboratory settings to facilitate its use as a diagnostic routine test in clinical practice.
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