Prevalence and Significance of Serum 14-3-3η in Juvenile Idiopathic Arthritis

Abstract Background: Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14-3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14-3-3η in different types of JIA.Methods: JIA patients (n=151) followed by the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n=39), PJIA RF- (n=39), psoriatic arthritis (PsA; n=19), enthesitis-related arthritis (ERA; n=18), and oligoarticular JIA (OJIA [control group]; n=36). RF, CCP antibody, and 14-3-3η were measured for all patients. 14-3-3η serum levels >0.2ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). Results: Elevated 14-3-3h levels were detected in 34/151 (23%) patients, and across all groups tested. Most patients with 14-3-3h had titers ≥4 times above the cutoff value. The majority (22, 65%) of 14-3-3h-positive patients were also positive for RF or CCP antibodies, 16 (47%) were positive for all 3, and 12 (35%) were single-positive for 14-3-3η. The highest prevalence of 14-3-3η was in PJIA RF+ patients (49%), followed by OJIA (22%). Positivity for 14-3-3h was not significantly associated with disease activity or age at diagnosis. Conclusion: Serum 14-3-3h can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14-3-3h does not appear to correlate with disease activity in JIA.

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Prevalence and significance of serum 14–3-3η in juvenile idiopathic arthritis

Pediatric Rheumatology ◽

10.1186/s12969-021-00502-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Iris Reyhan ◽

Olga S. Zhukov ◽

Robert J. Lagier ◽

Robert F. Bridgforth ◽

Gary J. Williams ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Los Angeles ◽

Disease Activity ◽

Elevated Serum ◽

Serum Levels ◽

Control Group ◽

Adult Rheumatoid Arthritis ◽

Single Positive ◽

Prompt Diagnosis

Abstract Background Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14–3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14–3-3η in different types of JIA. Methods JIA patients (n = 151) followed by the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 19), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14–3-3η were measured for all patients. 14–3-3η serum levels > 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71). Results Elevated 14–3-3η levels were detected in 34/151 (23%) patients, and across all groups tested. Most patients with 14–3-3η had titers ≥4 times above the cutoff value. The majority (22, 65%) of 14–3-3η-positive patients were also positive for RF or CCP antibodies, 16 (47%) were positive for all 3, and 12 (35%) were single-positive for 14–3-3η. The highest prevalence of 14–3-3η was in PJIA RF+ patients (49%), followed by OJIA (22%). Positivity for 14–3-3η was not significantly associated with disease activity or age at diagnosis. Conclusion Serum 14–3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14–3-3η does not appear to correlate with disease activity in JIA.

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Prevalence and Significance of Serum 14-3-3η(eta) in Juvenile Idiopathic Arthritis

10.21203/rs.3.rs-26035/v1 ◽

2020 ◽

Author(s):

Iris Reyhan ◽

Olga S. Zhukov ◽

Robert J. Lagier ◽

Robert F. Bridgeforth ◽

Joanna M. Popov ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Los Angeles ◽

Disease Activity ◽

Elevated Serum ◽

Serum Levels ◽

Control Group ◽

Adult Rheumatoid Arthritis ◽

Single Positive ◽

Prompt Diagnosis

Abstract Background Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14-3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14-3-3η in different types of JIA.Methods JIA patients (n = 152) followed by the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 20), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14-3-3η were measured for all patients. 14-3-3η serum levels ≥ 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71).Results Elevated 14-3-3η levels were detected in 35/152 (23%) patients, and across all groups tested. Most patients with 14-3-3η had titers ≥ 4 times above the cutoff value. The majority (23, 67%) of 14-3-3η-positive patients were also positive for RF or CCP antibodies, 17 (49%) were positive for all 3, and 12 (8%) were single-positive for 14-3-3η. The highest prevalence of 14-3-3η was in PJIA RF + patients (49%), followed by OJIA (22%). Positivity for 14-3-3η was not significantly associated with disease activity or age at diagnosis.Conclusion Serum 14-3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14-3-3η does not appear to correlate with disease activity in JIA.

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FRI0564 SERUM LEVELS OF IL-6 AND IL-8 IN ANKYLOSING SPONDYLITIS PATIENTS: ASSOCIATIONS WITH DISEASE ACTIVITY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3082 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 884.1-885

Author(s):

E. Aleksandrova ◽

A. Novikov ◽

P. Kulakova ◽

A. Dorofeev ◽

N. Savenkova ◽

...

Keyword(s):

New York ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Heart Diseases ◽

Elevated Serum ◽

Serum Levels ◽

Fecal Calprotectin ◽

Chronic Inflammatory Disease ◽

Control Group ◽

Inflammatory Bowel

Background:Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine and sacroiliac joints characterized by new bone formation (syndesmophytes) and ankyloses. In AS cases, along with the damage to the musculoskeletal system, impairment of other organs and systems is often observed (uveitis, inflammatory bowel and heart diseases). Pro-inflammatory cytokines (TNF-α, IL-6,-17,-23,-21,-22,-31) and chemokines (IL-8) are key pathogenic markers in AS.Objectives:The aims of the study were to determine the serum levels of IL-6 and IL-8 in AS and investigate their relationship with disease activity.Methods:We studied 140 patients (pts) with AS fulfilled modified New York criteria (1984); (102M/38F); median and interquartile range (25th—75th percentile) of age 43.0; 35.0-51.0 years; disease duration 6.0; 4.0-12.0 years; BASDAI - 5.4; 4.1-6.6; ASDAS ESR - 3.6; 2.6-4.4; ASDAS CRP - 3.8; 2.7-4.5; 86% HLA-27 positive. In 50% of pts with AS, inflammatory bowel diseases (IBD) (Crohn’s disease and ulcerative colitis) were diagnosed. The control group included 17 healthy donors (HC). The serum concentrations of IL-6 and IL-8 were detected by chemiluminescence immunoassay using IMMULATE 1000 analyzer (Siemens Healthcare Diagnostics, USA).Results:AS pts had significantly higher serum level of IL-6 than HC (4.3; 0.1-8.0 pg/ml vs 2.3; 0.1-2.7 pg/ml, p <0.006). The median concentration of IL-8 didn’t differ between AS pts and HC (10.5; 8.3-18.0 pg/ml vs 11.9; 8.2-18.3 pg/ml, p>0.05). The same levels of IL-6 and IL-8 were detected in AS with IBD and AS without signs of IBD (p>0.05). In AS pts, serum IL-6 concentration was positively correlated with ASDAS ESR (r = 0.3), ASDAS CRP (r = 0.3), ESR (r = 0.3) and CRP (r = 0.5) (p <0.05); IL-8 was negatively associated with presence of fecal calprotectin (r = -0.3) (p <0.05).Conclusion:Elevated serum concentration of IL-6 in AS is associated with clinical and laboratory markers of high inflammatory activity of the disease. The levels of IL-8 in the sera of AS patients were negatively correlated with the concentration of fecal calprotectin. Data on the relationship of IL-8 with the activity of the pathological process in AS require further study.Disclosure of Interests:Elena Aleksandrova: None declared, Alexander Novikov: None declared, Polina Kulakova: None declared, Aleksey Dorofeev: None declared, Nadezhda Savenkova: None declared, Evgeniy Volnukhin: None declared, Anton Kovshik: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche

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AB0837 SERUM YKL-40 LEVELS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: RELATION TO DISEASE ACTIVITY AND JOINT DESTRUCTION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2069 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1442.2-1443

Author(s):

E. Aleksandrova ◽

A. Novikov ◽

E. Luchikhina ◽

D. Karateev ◽

G. Lukina

Keyword(s):

Rheumatoid Arthritis ◽

Serum Level ◽

Disease Activity ◽

Joint Destruction ◽

Elevated Serum ◽

Serum Levels ◽

Control Group ◽

Human Cartilage ◽

Amyloid A ◽

Early Ra

Background:YKL-40 (chitinase-3-like 1 protein, human cartilage glycoprotein 39) is one of the major proteins secreted locally in the arthritic joint by activated macrophages, chondrocytes, synoviocytes and neutrophils, YKL-40 an important marker for inflammation, cartilage remodelling and synovial hyperplasia is recognized as a possible auto-antigen in rheumatoid arthritis (RA).Objectives:The aims of the study were to determine the serum level of YKL-40 in early RA and investigate his relationship with biomarkers of disease activity and joint destruction.Methods:We studied 22 patients with early RA (ACR/EULAR 2010 classification criteria); 4 males, 18 females; median and interquartile range (25th—75th percentile) of age 55,0 (43,0-64,0) years, disease duration 7,0 (5,0-11,0) months, DAS28 4,9 (4,3-5,8); 86% IgM rheumatoid factor (IgM RF) +; 91% anti-cyclic citrullinated peptide antibody (anti-CCP) +. All patients were treated with methotrexate (MTX). Three (14 %) patients received low oral doses of steroids and intra-articular injections. The control group included 22 healthy donors (HC). Radiographs were scored according to the van der Heijde-modified Sharp score. YKL-40, matrix metalloproteinase-3 (MMP-3), anti-CCP were detected using commercially available enzyme-linked immunosorbent assays (ELISA). The serum levels of IgM RF, C-reactive protein (CRP), serum amyloid A (SAA) were measured by immunonephelometry.Results:RA patients had significantly higher serum level of YKL-40 than HC (92,1; 68,5-153,1 pg/ml vs 54,0; 41,7-83,2 pg/ml, p<0.01). Serum YKL-40 concentration was positively correlated with DAS 28 (r=0,5; p<0,05), erythrocyte sedimentation rate (ESR) (r=0,5; p<0,05), CRP (r=0,8; p<0,05), SAA (r=0,6; p<0,05) and MMP-3 (r = 0,6; p<0,05). We found no relationship between the level of YKL-40 and articular radiographic changes.Conclusion:Elevated serum concentration of YKL-40 in early RA is associated with clinical and laboratory indicators of disease inflammatory activity and increased level of MMP-3 - an immunological marker of joint destruction.Disclosure of Interests:Elena Aleksandrova: None declared, Alexander Novikov: None declared, Elena Luchikhina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Consultant of: Abbvie, Biocad, Sanofi, Celgene, Dmitriy Karateev Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Lilly, Bayer, Paid instructor for: Abbvie, Pfizer, Biocad, Sanofi, Novartis, Lilly, Galina Lukina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Paid instructor for: Abbvie, Biocad, Sanofi, Celgene

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Seroprevalence of Antibodies against SARS-CoV-2 in Children with Juvenile Idiopathic Arthritis a Case-Control Study

Journal of Clinical Medicine ◽

10.3390/jcm10081771 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1771

Author(s):

Violetta Opoka-Winiarska ◽

Ewelina Grywalska ◽

Izabela Korona-Glowniak ◽

Katarzyna Matuska ◽

Anna Malm ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Disease Activity ◽

Disease Activity Score ◽

Juvenile Arthritis ◽

Activity Score ◽

Control Group ◽

Healthy Children ◽

Serum Samples ◽

History Of ◽

Novel Coronavirus

There is limited data on the effect of the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) on pediatric rheumatology. We examined the prevalence of antibodies against SARS-CoV-2 in children with juvenile idiopathic arthritis (JIA) and a negative history of COVID-19 and the correlation of the presence of these antibodies with disease activity measured by juvenile arthritis disease activity score (JADAS). In total, 62 patients diagnosed with JIA, under treatment with various antirheumatic drugs, and 32 healthy children (control group) were included. Serum samples were analyzed for inflammatory markers and antibodies and their state evaluated with the juvenile arthritis disease activity score (JADAS). JIA patients do not have a higher seroprevalence of anti-SARS-CoV-2 antibodies than healthy subjects. We found anti-SARS-CoV-2 antibodies in JIA patients who did not have a history of COVID-19. The study showed no unequivocal correlation between the presence of SARS-CoV-2 antibodies and JIA activity; therefore, this relationship requires further observation. We also identified a possible link between patients’ humoral immune response and disease-modifying antirheumatic treatment, which will be confirmed in follow-up studies.

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Increased Serum Interleukin 22 in Patients with Rheumatoid Arthritis and Correlation with Disease Activity

The Journal of Rheumatology ◽

10.3899/jrheum.111027 ◽

2012 ◽

Vol 39 (7) ◽

pp. 1320-1325 ◽

Cited By ~ 60

Author(s):

LAURINDO FERREIRA da ROCHA ◽

ÂNGELA LUZIA BRANCO PINTO DUARTE ◽

ANDRÉA TAVARES DANTAS ◽

HENRIQUE ATAÍDE MARIZ ◽

IVAN da ROCHA PITTA ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Mononuclear Cells ◽

Activity Index ◽

Elevated Serum ◽

Serum Levels ◽

Peripheral Blood Mononuclear ◽

Additional Tool ◽

Bone Erosions ◽

Interleukin 22

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.

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What is the impact of methotrexate on liver in patients with juvenile idiopathic arthritis? Results of liver SWE performed in a single centre

Modern Rheumatology ◽

10.1093/mr/roab064 ◽

2021 ◽

Author(s):

Vildan Güngörer ◽

Mehmet Öztürk ◽

Mustafa Yasir Özlü ◽

Şükrü Arslan

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Shear Wave Elastography ◽

Term Therapy ◽

Control Group ◽

Significant Difference ◽

Group 2 ◽

Long Term Therapy ◽

And Control ◽

The Impact

ABSTRACT Objectives Long-term therapy with low-dose methotrexate (MTX) is widely used in treatment of rheumatic diseases, in children. The purpose of this study was to evaluate liver elasticity in patients with juvenile idiopathic arthritis (JIA) who received MTX and compare the results with control group. Methods Liver elasticity was evaluated with shear wave elastography (SWE) technique in 25 patients aged 3–17 years who were followed up with JIA and received MTX and compared with 25 healthy controls of the same age and weight. Factors that had an effect on liver elasticity were examined. Results The mean SWE value of patients was 2.64 ± 2.13 m/s and 24.10 ± 18.50 kPa, whereas 1.83 ± 0.16 m/s and 10.09 ± 1.83 kPa in control group. There was a significant difference in liver elasticity in the patient and control groups. When the patients were evaluated as Group 1 (< 1000 mg) and Group 2 (≥ 1000 mg) according to the cumulative MTX dose, no significant difference was obtained. There was positive correlation between liver elasticity and weekly MTX dose and age. Conclusions Our study revealed that liver elasticity significantly decreased in patients who received MTX when compared with the control group. The elastography technique will be understood better over time and used safely in many areas.

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