Novel approaches to gene expression analysis of active polyarticular juvenile rheumatoid arthritis

Arthritis Research & Therapy

James N Jarvis¹  Igor Dozmorov³  Kaiyu Jiang¹  Mark Barton Frank³  Peter Szodoray²  Philip Alex³  Michael Centola³ 

[1] Department of Pediatrics, University of Oklahoma College of Medicine, Oklahoma City, OK, USA

[2] Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway

[3] Department of Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

关键词: microarray;    juvenile rheumatoid arthritis;    bioinformatics;    autoimmunity;    arthritis;   

Others  :  1101319
DOI  :  10.1186/ar1018

 received in 2003-05-30, accepted in 2003-10-02,  发布年份 2003

【 摘 要 】

Juvenile rheumatoid arthritis (JRA) has a complex, poorly characterized pathophysiology. Modeling of transcriptosome behavior in pathologic specimens using microarrays allows molecular dissection of complex autoimmune diseases. However, conventional analyses rely on identifying statistically significant differences in gene expression distributions between patients and controls. Since the principal aspects of disease pathophysiology vary significantly among patients, these analyses are biased. Genes with highly variable expression, those most likely to regulate and affect pathologic processes, are excluded from selection, as their distribution among healthy and affected individuals may overlap significantly. Here we describe a novel method for analyzing microarray data that assesses statistically significant changes in gene behavior at the population level. This method was applied to expression profiles of peripheral blood leukocytes from a group of children with polyarticular JRA and healthy control subjects. Results from this method are compared with those from a conventional analysis of differential gene expression and shown to identify discrete subsets of functionally related genes relevant to disease pathophysiology. These results reveal the complex action of the innate and adaptive immune responses in patients and specifically underscore the role of IFN-γ in disease pathophysiology. Discriminant function analysis of data from a cohort of patients treated with conventional therapy identified additional subsets of functionally related genes; the results may predict treatment outcomes. While data from only 9 patients and 12 healthy controls was used, this preliminary investigation of the inflammatory genomics of JRA illustrates the significant potential of utilizing complementary sets of bioinformatics tools to maximize the clinical relevance of microarray data from patients with autoimmune disease, even in small cohorts.

【 授权许可】

   
2004 Jarvis et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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