Gene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis.
OBJECTIVE
We have previously reported a defect in neutrophil activation in children with polyarticular juvenile idiopathic arthritis (JIA). The current study was undertaken to determine whether gene expression abnormalities persist in JIA in remission and to use systems biology analysis to elucidate pathologic pathways in polyarticular JIA.


METHODS
We performed gene expression profiling on neutrophils from children with polyarticular JIA. Children were grouped according to disease status. We studied 14 children with active disease who were taking medication, 8 children with clinical remission of disease who were taking medication (CRM status), and 6 children with clinical remission of disease who were not taking medication (CR status). We also studied 13 healthy children whose age ranges overlapped those of the patients.


RESULTS
Neutrophil abnormalities persisted in children with polyarticular JIA even after disease remission was achieved. Children with active disease and those with CRM status showed no differences in expression of specific genes, although they could be separated on cluster analysis. A comparison of children with CR status and healthy control children revealed networks of pro- and antiinflammatory genes that suggested that remission is a state of homeostasis and balance rather than a return to normal immune function. Furthermore, gene overexpression in patients with CR status supports the hypothesis that neutrophils play a role in regulating adaptive immunity in this disease.


CONCLUSIONS
Neutrophil gene profiling in polyarticular JIA suggests important roles for neutrophils in disease pathogenesis. These findings suggest the presence of complex interactions between innate and adaptive immunity, that are not easily modeled in conventional, linear, reductionist systems.
Jarvis
James N
JN
Pediatric Rheumatology Research, College of Medicine, Children's Hospital of Oklahoma, University of Oklahoma, Oklahoma City, OK 73013, USA. james-jarvis@ouhsc.edu
Jiang
Kaiyu
K
Frank
Mark Barton
MB
Knowlton
Nicholas
N
Aggarwal
Amita
A
Wallace
Carol A
CA
McKee
Ryan
R
Chaser
Brad
B
Tung
Catherine
C
Smith
Laura B
LB
McGhee
Julie L
JL
Chen
Yanmin
Y
Osban
Jeanette
J
O'Neil
Kathleen M
KM
Centola
Michael
M
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D009504:Neutrophils / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction