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‫ نموذج للملخصات البحثية إنجليزي‬: 1‫مرفق‬
Title
Low serum levels of NT-proCNP in children with poly-articular onset juvenile
rheumatoid arthritis.
Author-s
Fozia Khan, Ann Pokelsek,Lori Galla, Mary Toth, Hulya Bukulmez,
Contact lnfo
[email protected]
Department
Pediatric Rheumatology, Department of Pediatrics, MetroHealth Medical Center, Case
Western Reserve University, Cleveland, Ohiohttp://dent.ksu.edu.sa/faculty_en
Major
Biochemistry
citation
In process
Year of
Publication
2012
Publisher
Sponsor
Type of
Publication
Research Article
ISSN
URI/DOI
Full Text
(Yes,No)
Key words
Abstract
C-type Natriuretic Peptide, juvenile rheumatoid arthritis
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 (NTproCNP) 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 zscores, cytokines and laboratory data.
All patients with JRA had low NT-proCNP z-scores compared to age matched controls. Polyand 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 polyarticular 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.