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

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

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Activity of systemic juvenile idiopathic arthritis in children immunized with pneumococcal 13-valent conjugate vaccine: prospective cohort study

Voprosy praktičeskoj pediatrii ◽

10.20953/1817-7646-2020-5-40-50 ◽

2020 ◽

Vol 15 (5) ◽

pp. 40-50

Author(s):

D.D. Vankova ◽

◽

E.I. Alekseeva ◽

T.M. Dvoryakovskaya ◽

R.V. Denisova ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Disease Activity ◽

Conjugate Vaccine ◽

Systemic Juvenile Idiopathic Arthritis ◽

High Sensitivity ◽

C Reactive Protein ◽

Reactive Protein ◽

Significant Difference ◽

Hs Crp ◽

Active Disease

Evaluation of the safety profile of vaccines in patients with rheumatic diseases requires an assessment of their impact on disease activity. The effect of antipneumococcal vaccination on the activity of systemic juvenile idiopathic arthritis (sJIA) has not been studied so far. Objective. To evaluate the dynamics of sJIA activity after immunization with pneumococcal 13-valent conjugate vaccine (PCV13) of patients receiving biologicals. Patients and methods. This study included patients with sJIA in remission or active disease receiving biologicals during inpatient treatment and vaccinated with PCV13. To evaluate the effect of immunization on sJIA activity, we measured serum levels of high-sensitivity C-reactive protein (hs-CRP) and calprotectin. In addition to that, we assessed the number of new cases, when concentration of these markers was above the upper limit (UL) 4 weeks after PCV13 administration. Results. In 18 out of 53 patients in remission (34%) and 3 out of 25 patients with active sJIA (12%), hs-CRP levels were undetectable (0.1 mg/L) at both time-points (baseline and after 4 weeks). Among those with detectable hs-CRP levels in at least one time-point 4 weeks after vaccination, patients in remission (n = 35) had no significant changes in hs-CRP (median -0.17 mg/mL; 95% CI -0.84…0.41), whereas patients with active sJIA (n = 22) demonstrated a 3-fold decrease in hs-CRP level (median -0.94 mg/mL (95% CI -3.93…0.05). We observed no significant difference in calprotectin levels in the groups. Concentration of hs-CRP above the UL 4 weeks after vaccination was detected in 2 out of 53 sJIA patients in remission (4%) and none of the patients with active sJIA. Сoncentration of calprotectin above the UL 4 weeks after vaccination was detected in 8 out 53 (15%) and 5 out 25 (20%) sJIA patients in remission and with active disease, respectively. Conclusion. Vaccination against pneumococcal infection in patients with sJIA led to an increase in the level of highly sensitive laboratory markers of sJIA activity in 4–20% of patients. Key words: disease activity, safety, high-sensitivity C-reactive protein, biological drugs, calprotectin, juvenile idiopathic arthritis, pneumococcal 13-valent conjugate vaccine

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Serum Leucine-Rich α2-Glycoprotein as a Biomarker for Monitoring Disease Activity in Patients with Systemic Juvenile Idiopathic Arthritis

Journal of Immunology Research ◽

10.1155/2019/3140204 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Masaki Shimizu ◽

Natsumi Inoue ◽

Mao Mizuta ◽

Yasuo Nakagishi ◽

Akihiro Yachie

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Disease Activity ◽

Influenza A ◽

Systemic Juvenile Idiopathic Arthritis ◽

C Reactive Protein ◽

Serum Cytokine ◽

Tumor Necrosis Factor Receptors ◽

Reactive Protein ◽

Cytokine Levels ◽

Necrosis Factor

To investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are useful as a marker of disease activity in systemic juvenile idiopathic arthritis (s-JIA), we determined serum LRG levels in fifty-nine s-JIA patients, 15 with other subtypes of JIA, 7 with Kawasaki disease (KD), 7 with influenza A infection (flu), 7 with enterohemorrhagic Escherichia coli (EHEC) infection, and 20 healthy controls (HC). Results were compared with the clinical features of s-JIA and serum cytokine levels including interleukin- (IL-) 6, IL-18, and soluble tumor necrosis factor receptors I and II. Serum LRG levels in active s-JIA were higher compared to those in other subtypes of JIA, EHEC, flu patients, and HC. Serum LRG levels were normalized in the inactive s-JIA phase after treatment. Serum LRG levels were positively correlated with serum C-reactive protein and ferritin levels. Serum LRG levels reflected s-JIA disease activity and thus may be useful for monitoring s-JIA disease activity.

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

Mediators of Inflammation ◽

10.1155/2021/6650928 ◽

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.

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An Evaluation of the Correlation between Hepcidin Serum Levels and Disease Activity in Inflammatory Bowel Disease

Gastroenterology Research and Practice ◽

10.1155/2015/810942 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 11

Author(s):

Zehra Betül Paköz ◽

Cem Çekiç ◽

Mahmut Arabul ◽

Elif Sarıtaş Yüksel ◽

Serkan İpek ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Disease Activity ◽

Bowel Disease ◽

Active Phase ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

C Reactive Protein ◽

Reactive Protein ◽

Inflammatory Bowel ◽

The Mean

Aim. While there are many well-defined serological markers for inflammatory bowel disease (IBD), there is limited evidence that they positively affect clinical outcomes. This study aimed to evaluate the correlation between hepcidin serum levels and disease activity in IBD.Materials and Methods. Eighty-five consecutive IBD patients were enrolled in the study. Hepcidin serum levels were assessed using an enzyme-linked immunosorbent assay (ELISA) and were compared with disease activity as well as the interleukin-6 (IL-6) and C-reactive protein (CRP) levels.Results. The mean hepcidin serum levels in Crohn’s disease (CD) patients in remission and in the active phase were3837±1436and3752±1274 pg/mL, respectivelyP=0.613. The mean hepcidin serum levels in ulcerative colitis (UC) patients in remission and in the active phase were4285±8623and3727±1176 pg/mL, respectivelyP=0.241. Correlation analysis between inflammatory markers and hepcidin serum levels indicated that there was no correlation between hepcidin levels and IL-6P=0.582or CRPP=0.783.Conclusion. As an acute-phase protein, hepcidin seems to have a lower efficacy than other parameters in the detection of activation in IBD.

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Low Level of Vitamin D is Correlated with High C-Reactive Protein (CRP) and Disease Activity in Indonesian Juvenile Idiopathic Arthritis (JIA) Patients

The Indonesian Biomedical Journal ◽

10.18585/inabj.v12i2.1143 ◽

2020 ◽

Vol 12 (2) ◽

pp. 149-56

Author(s):

Desy Wulandari ◽

Wisnu Barlianto ◽

Tita Luthfia Sari

Keyword(s):

Vitamin D ◽

Juvenile Idiopathic Arthritis ◽

Serum Level ◽

Disease Activity ◽

Vitamin D Deficiency ◽

Control Group ◽

Healthy Children ◽

C Reactive Protein ◽

Low Level ◽

Reactive Protein

BACKGROUND: Vitamin D plays essential role in the regulation of inflammation, such as in pathogenesis of Juvenile Idiopathic Arthritis (JIA). Vitamin D deficiency has been reported among JIA patients, but there were conflicting results regarding the correlation with disease activity. This study aimed to assess vitamin D serum level and its correlation with C-Reactive Protein (CRP) and disease activity in JIA patients.METHODS: Children who were diagnosed with JIA according to International League of Associations for Rheumatology (ILAR) criterias were enrolled as JIA group subjects, while age and sex-matched healthy children were enrolled as the control group subjects. Vitamin D and CRP serum level were measured. Disease activity of JIA patients was calculated by Juvenile Arthritis Disease ActivityScore-27 (JADAS-27).RESULTS: Vitamin D serum level was lower in the JIA group compared to the healthy control group (p=0.000). Among 26 JIA patients, 61.5% were deficient, 30.8% were insufficient, and 7.7% had normal vitamin D. No significant different in CRP level between vitamin D group (p=0.441), but there was significant different in JADAS-27 (p=0.001). The mean of CRP and JADAS-27 were found highest in vitamin D deficiency group. Vitamin D serum level was negatively correlate with CRP (p=0.021, r=-0.452) and JADAS-27 (p=0.001 r=-0.595).CONCLUSION: Low level of vitamin D in JIA patients was inversely related to higher CRP and disease activity,suggesting that vitamin D supplementation could be havepotential role in JIA treatment.KEYWORDS: vitamin D, CRP, disease activity,JADAS-27, JIA

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13-valent Pneumococcal Conjugate Vaccine and Haemophilus Influenzae-Tetanus Toxoid Conjugate Vaccine in Patient with Systemic Juvenile Idiopathic Arthritis Receiving Tocilizumab: Clinical Case

Вопросы современной педиатрии ◽

10.15690/vsp.v18i3.2035 ◽

2019 ◽

Vol 18 (3) ◽

pp. 180-186

Author(s):

Ekaterina I. Alekseeva ◽

Dar’ya D. Van’kova ◽

Tatyana M. Dvoryakovskaya ◽

Kseniya B. Isaeva ◽

Rina V. Denisova ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Haemophilus Influenzae ◽

Conjugate Vaccine ◽

Tetanus Toxoid ◽

Pneumococcal Conjugate Vaccine ◽

Clinical Case ◽

Systemic Juvenile Idiopathic Arthritis ◽

Infectious Complications ◽

C Reactive Protein ◽

Reactive Protein

Background. Vaccination coverage in patients with rheumatic diseases remains extremely low. Moreover, infections are the leading cause of death in such patients. Respiratory infections mortality is 2–5 times higher in adults with rheumatoid arthritis than in overall population. The most frequent infectious complications in patients receiving Tocilizumab (first-line drug for treatment of patients with systemic juvenile idiopathic arthritis (SJIA)) are pneumonia and acute sinusitis. Their clinical course differs: slight clinical presentation, reference ranges of laboratory tests of disease activity (ESR, C-reactive protein), significant changes in lungs and paranasal sinuses according to the computer tomography. Infectious complications development can cause aggravation of prior disease itself or due to temporary immunosuppressive therapy cessation. Clinical Case Description. The experience of immunization with 13-valent pneumococcal conjugate vaccine (PCV13) and haemophilus influenzae-tetanus toxoid conjugate vaccine in the 1,5 years old boy with SJIA receiving interleukin-6 receptor monoclonal antibody Tocilizumab is presented. The result of such vaccination was increase of pneumococcal and haemophilus influenzae antibodies levels by more than two times. Meanwhile vaccination had no negative impact on the prior disease course: the levels of predictors of prior disease aggravation such as protein S100 and highly sensitive C-reactive protein did not increase significantly in comparison with the period before vaccination. Conclusion. The efficiency and safety of immunization with PCV13 and haemophilus influenzae-tetanus toxoid conjugate vaccine in the child with SJIA receiving Tocilizumab is presented.

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Biomarkers of Bone Metabolism in Ankylosing Spondylitis in Relation to Osteoproliferation and Osteoporosis

The Journal of Rheumatology ◽

10.3899/jrheum.131199 ◽

2014 ◽

Vol 41 (7) ◽

pp. 1349-1356 ◽

Cited By ~ 51

Author(s):

Eva Klingberg ◽

Merja Nurkkala ◽

Hans Carlsten ◽

Helena Forsblad-d’Elia

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Bone Metabolism ◽

Activity Index ◽

Elevated Serum ◽

Serum Levels ◽

Spinal Mobility ◽

C Reactive Protein ◽

Mineral Density ◽

Reactive Protein

Objective.To identify biomarkers for bone metabolism in patients with ankylosing spondylitis (AS) and to determine the relationship between these biomarkers and disease activity, back mobility, osteoproliferation, and bone mineral density (BMD).Methods.Serum levels of Wingless protein (Wnt-3a), Dickkopf-1 (DKK-1), sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin were assessed using ELISA. Ankylosing Spondylitis Disease Activity Score-C reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis patient global score, and C-reactive protein (CRP) were used as disease activity measures, and Bath Ankylosing Spondylitis Metrology Index (BASMI) as a measure of spinal mobility. Lateral spine radiographs were scored for chronic AS-related changes (mSASSS). BMD was measured with dual-energy x-ray absorptiometry.Results.Two hundred four patients with AS (NY criteria; 57% men), with a mean age of 50 ± 13 years and disease duration 15 ± 11 years, and 80 age and sex-matched controls were included. The patients with AS had significantly higher serum levels of Wnt-3a (p < 0.001) and lower levels of sclerostin (p = 0.014) and sRANKL (p = 0.047) compared with the controls. High CRP was associated with low sclerostin (rS = −0.21, p = 0.003) and DKK-1 (rS = −0.14, p = 0.045). In multiple linear regression analyses, increasing BASMI and mSASSS were independently associated with older age, male sex, high CRP, and elevated serum levels of Wnt-3a. In addition, mSASSS remained associated with a high number of smoking pack-years after adjusting for age. Low BMD of femoral neck was associated with high mSASSS after adjusting for age.Conclusion.Serum levels of Wnt-3a are elevated in AS and associated with increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a biomarker for the osteoproliferative process.

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Decrease in Serum Interleukin-21 Levels Is Associated With Disease Activity Improvement in Patients With Recent-Onset Rheumatoid Arthritis

Physiological Research ◽

10.33549/physiolres.932701 ◽

2014 ◽

pp. 475-481 ◽

Cited By ~ 2

Author(s):

O. SGLUNDA ◽

H. F. MANN ◽

H. HULEJOVÁ ◽

O. PECHA ◽

L. PLEŠTILOVÁ ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Disease Activity Score ◽

Serum Levels ◽

Response To Treatment ◽

Healthy Individuals ◽

C Reactive Protein ◽

Recent Onset ◽

Reactive Protein ◽

Interleukin 21

Interleukin-21 (IL-21) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The aim of our study was to assess serum levels of IL-21 in patients with recent-onset RA in relation to disease activity and response to treatment. We analyzed serum levels of IL-21 in 51 RA patients, both before and 12 weeks after the initiation of treatment and in 36 healthy individuals. Disease activity was assessed at baseline and at weeks 12 and 24 using the Disease Activity Score for 28 joints, serum levels of C-reactive protein, and the total swollen joint count. We found that IL-21 levels were not increased in patients with recent-onset RA compared with healthy controls, but they had significantly decreased from baseline to week 12 during treatment. Baseline levels of IL-21 significantly correlated with measures of disease activity (p<0.02 for all). Although IL-21 levels did not predict achievement of remission, decrease in IL-21 levels correlated with improvement in disease activity after 12 weeks (p<0.02) and also after 24 weeks (p<0.04) of treatment. Our data suggest that circulating IL-21 levels may serve as a biomarker of disease activity and better outcome in early phase of RA.

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