Open AccessGene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis
Author(s) -
Jarvis James N.,
Jiang Kaiyu,
Frank Mark Barton,
Knowlton Nicholas,
Aggarwal Amita,
Wallace Carol A.,
McKee Ryan,
Chaser Brad,
Tung Catherine,
Smith Laura B.,
McGhee Julie L.,
Chen Yanmin,
Osban Jeanette,
O'Neil Kathleen M.,
Centola Michael
Publication year - 2009
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24450
Subject(s) - medicine , arthritis , disease , immunology , juvenile rheumatoid arthritis , pathogenesis , juvenile , acquired immune system , immune system , immunity , gene expression profiling , gene , gene expression , biology , genetics
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. Conclusion 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.