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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/18673

Title: Low serum levels of NT-proCNP in children with poly-articular onset juvenile rheumatoid arthritis.
Authors: Khan, Fozia.
Pokelsek, Ann.
Galla, Lori.
Toth, Mary.
Bukulmez, Hulya
Keywords: C-type Natriuretic Peptide, juvenile rheumatoid arthritis
Issue Date: 2012
Citation: In process
Abstract: Children with juvenile rheumatoid arthritis (JRA) develop longitudinal growth delay. Increased levels of proinflammatory cytokines (IL-6, TNF-α) in serum and in synovial fluid have been blamed for suppressing the local and/or systemic growth factors that regulate endochondral bone growth. Aside from growth hormone signaling pathway, it is unknown whether other growth factors that regulate the endochondral bone growth are affected in JRA. C-type natriuretic peptide (CNP) has been recently described as an essential paracrine factor for normal endochondral bone growth. Serum level of N-terminal pro-peptide of CNP (NT-proCNP) has been suggested to be a marker for endochondral bone growth. In this study, we aimed to investigate whether CNP signaling is affected during active juvenile inflammatory arthritis in children by measuring the serum NT-proCNP levels during active disease and investigated whether serum NT-proCNP levels correlated with the serum IL-6 and TNF-alpha levels. Clinical and laboratory data was collected from children diagnosed with juvenile rheumatoid arthritis (JRA) according to ACR criteria (n=18, 9 pauci-articular, 8 poly-articular, and 1 systemic onset JRA). Concurrent clinical and laboratory data were collected from patients during their enrollment in the study as a part of their routine care. Pro-inflammatory cytokine levels and the NT-proCNP levels were measured using ELISA. Z-scores of NT-proCNP levels for each patient were calculated using NT-proCNP levels of age matched healthy children. Statistical analysis software was used (SAS 9.2) to calculate the correlations between the z-scores, cytokines and laboratory data. All patients with JRA had low NT-proCNP z-scores compared to age matched controls. Poly- and systemic JRA patient’s z-scores were significantly lower. IL-6 levels showed negative correlation with the z-scores in children with poly-JRA (r= -0.67, p=0.06). When stratified for gender, correlation of z-scores with IL-6 level became significant (r=-0.99, p=0.034). Sedimentation levels correlated with TNF-α levels in poly-JRA patients (r=0.91, p=0.003), but TNF-α levels correlation with NT-proCNP z-scores did not reach statistical significance. Seven of eight poly-JRA patients were under treatment with Methotrexate (20mg/m2) and five were also treated with oral prednisone (>0.5mg/kg/d). The mean z-scores of NT-proCNP in patients who used prednisone (n=5) were not different than those who did not use prednisone (n=3). Serum NT-proCNP levels of children with JRA are lower than age matched controls. In poly-articular onset JRA patients, the serum levels of IL-6 show negative correlation with z-scores of NT-proCNP. In addition to ongoing systemic inflammation, patients with poly-JRA were also being treated with medications such as methotrexate and prednisone which might lower the NT-proCNP levels. Further studies with larger JRA patient population are necessary to further delineate the disruption of CNP signaling during JRA. Serum NT-proCNP levels could be a biomarker for endochondral bone growth in children with JRA.
URI: http://hdl.handle.net/123456789/18673
Appears in Collections:College of Applied Medical Sciences

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