Gene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis
| Autor: | Mark Barton Frank, Nicholas Knowlton, Jeanette Osban, Julie L McGhee, Laura B. Smith, Carol A. Wallace, Amita Aggarwal, Brad Chaser, Catherine Tung, Yanmin Chen, James N. Jarvis, Ryan McKee, Kaiyu Jiang, Kathleen M. O'Neil, Michael Centola |
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| Rok vydání: | 2009 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Adolescent Neutrophils Immunology Population Arthritis Disease medicine.disease_cause Article Autoimmunity Pathogenesis Rheumatology Internal medicine medicine Immunology and Allergy Cluster Analysis Humans Pharmacology (medical) skin and connective tissue diseases education Child education.field_of_study business.industry Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Acquired immune system medicine.disease Arthritis Juvenile Child Preschool business Juvenile rheumatoid arthritis |
| Zdroj: | Arthritis and rheumatism. 60(5) |
| ISSN: | 0004-3591 |
| Popis: | Juvenile idiopathic arthritis (JIA) is a term used to denote a family of diseases of unknown etiology characterized by chronic inflammation of synovial membranes (1). Distinct phenotypes are recognized clinically, with specific immunogenetic markers associated with each of the phenotypes (2,3). While the JIA subtypes have commonly been assumed to have an “autoimmune” origin, our growing understanding of biologic complexity makes any such simple, linear hypothesis of disease pathogenesis unlikely (4). We have hypothesized that the pathogenesis of a common JIA subtype, polyarticular disease, involves complex interactions between innate and adaptive immunity not readily subsumed under a simple “autoimmunity” model (5,6). In support of this notion, we have demonstrated the presence of a population of hyperreactive neutrophils in children with polyarticular-onset JIA (7). Given our growing knowledge of how neutrophils regulate adaptive immunity (8), it is plausible to hypothesize that these abnormal neutrophils have a significant effect on adaptive immune mechanisms and the disease course in polyarticular JIA. The disease process in polyarticular JIA as seen in the normal clinical setting is not static. That is, children can be categorized based on their disease activity and response to therapy (i.e., active disease, inactive disease, remission of disease while taking medication, remission of disease while not taking medication), as Wallace and colleagues have shown (9). We have recently demonstrated that these clinically derived criteria for disease state have objective biologic identities, based on gene transcription profiling in peripheral blood mononuclear cells (PBMCs) (10). Thus, we have hypothesized that a practical way of gaining insight into the potential role of neutrophils in JIA pathogenesis is to study their function in specific disease states in conjunction with PBMCs. In the current study, we used a systems biology approach (gene transcription profiling and in silico modeling) to determine whether and how the neutrophil function may be altered in polyarticular JIA at different stages of the disease. |
| Databáze: | OpenAIRE |
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