Researchers now have data to support the hypothesis that, in patients with simultaneous systemic and arthritic components of systemic juvenile idiopathic arthritis (SJIA), these components are related mechanistically. Moreover, the inflammatory pathways of SJIA appear to be distinct from those seen in polyarticular JIA.
Xuefeng B. Ling, PhD, working with colleagues in the laboratory of Elizabeth D. Mellins, MD, in Stanford University in Stanford, Calif., identified only a limited number of SJIA genes that were related to erythrocyte sedimentation rate (ESR) in both SJIA and polyarticular JIA.1 These results are consistent with what rheumatologists have long known: SJIA is very different from other forms of JIA. The intriguing aspect of the study is that these differences could be visualized at the molecular level.
The data are also consistent with the hypothesis that SJIA is an autoinflammatory disease and polyarticular JIA is an autoimmune disease. The difference is reflected in the dysregulation of the innate immune system, which appears to contribute largely to the pathology of SJIA. In contrast, the adaptive immune responses appear to underlie the pathology of oligoarticular and polyarticular JIA. As an example of this difference, many children with polyarticular JIA have autoantibodies whereas patients with SJIA do not have autoantibodies.
Clinicians have long observed that, in many patients, SJIA begins as systemic inflammation and transitions into chronic joint disease with less systemic inflammation. The data from Dr. Mellins’ laboratory suggest that the differences in early and late arthritis in patients with SJIA may reflect immunobiology that evolves over the course of SJIA. It would follow that patients experiencing early SJIA versus those with late SJIA might benefit from different treatments.
Consider the Implications
When asked about the clinical implications of her work, Dr. Mellins emphasizes that the work is very early. She elaborates, “These results echo what clinicians have known, which is that SJIA is unique among JIA subtypes. … Results from some clinical research studies have proposed that children with chronic arthritis are less responsive to anti–interleukin-1, that there is a ‘window of opportunity’ for optimal response. Our work would argue that there is a biological reason for that.”
A notable aspect of the study is that it utilized kinetic polymerase chain reaction to analyze gene expression and related that expression to individual clinical parameters (e.g., ESR). Such an approach may continue to be useful when analyzing complex diseases such as SJIA.
The study analyzed gene expression in peripheral blood mononuclear cells (PBMCs). Dr. Mellins justifies the use of PBMCs as being reflective of the systemic nature of SJIA, suggesting that the blood is a reasonable window into the disease. This strategy was supported by the signal differences that were measured in the study. Dr. Mellins acknowledged, however, that “It would be great to be able to look directly at the cells in joints.” The fact that, typically, there is no clinical reason to get samples from the joints makes it difficult to justify such an approach. This limitation in the study design underscores the need for a good animal model for SJIA.
Dr. Pullen is a medical writer based in the Chicago area.
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