Gene Signature Identified for Juvenile Arthritis

The genes that are expressed in patients with systemic juvenile idiopathic arthritis (SJIA) have been compared with those with the more common polyarticular juvenile idiopathic arthritis (POLY).

The distinct pathways involved in the arthritis of early and established SJIA raise the possibility that the immune system alters its behavior over the course of this disease and this can be investigated by finding which genes are involved in increased erythrocyte sedimentation rate (ESR).

In a collaboration between the Stanford University School of Medicine (CA, USA) and Celera Corporation (Alameda, CA, USA), scientists looked at the genes switched on in the blood of children with either SJIA or POLY. Ribonucleic acid (RNA) from peripheral blood mononuclear cells (PBMC) of children with each disease was profiled by kinetic polymerase chain reaction (PCR) to analyze expression of 181 genes, selected for relevance to immune response pathways.

The team found 91 ESR-related and 92 joint count (JC)-related genes in SJIA, and for POLY, 20 ESR-related and zero JC-related genes were found. These genes were grouped into biological pathways such as interleukin (IL)-signaling, cluster of differentiation 40 (CD40)-signaling, or communication between immune cells. Therefore, it became apparent that in SJIA, these pathways were involved in elevated ESR, which is used as a marker for disease flare-up, and also linked to joint arthritis.

Elizabeth D. Mellins, MD, the senior author, said, "In our study we identified molecular pathways involved in both the systemic and arthritic components of SJIA. We discovered that the set of pathways involved in SJIA inflammation were different from those in POLY, perhaps explaining the differences in affected organs. This was especially true for the genes involved in increased ESR. For example, glucocorticoid signaling was more heavily involved in inflammation associated with SJIA than POLY, which may explain why nonglucocorticoid treatment is less effective for children with SJIA."

The authors concluded that even within the SJIA group different pathways were involved in different stages of the disease and knowledge like this should help refine treatment plans for these children and help to control their disease. The study was published on October 23, 2012, in the journal BMC Medicine.

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Stanford University School of Medicine
Celera Corporation