Journal
ARTHRITIS AND RHEUMATISM
Volume 58, Issue 5, Pages 1505-1515Publisher
WILEY-LISS
DOI: 10.1002/art.23437
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Funding
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
- Telethon [GGP07236] Funding Source: Medline
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Objective. To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1 beta and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA). Methods. Twenty-two patients with systemiconset JIA were treated with the IL-1 receptor antagonist (IL-1Ra) anakinra. Monocytes from 18 patients and 20 healthy donors were activated by different Toll-like receptor ligands. Intracellular and secreted IL-1 beta and IL-18 were analyzed by Western blotting and enzyme-linked immunosorbent assay. Results. Ten patients with systemic-onset JIA exhibited a dramatic response to anakinra and were classified as complete responders. Eleven patients had an incomplete response or no response, and I patient could not be classified in terms of response. Compared with patients who had an incomplete response or no response, complete responders had a lower number of active joints (P = 0.02) and an increased absolute neutrophil count (P = 0.02). In vitro IL-1 beta and IL-18 secretion in response to various stimuli was not increased and was independent of treatment efficacy. Likewise, secretion of IL-1Ra by monocytes from patients with systemic-onset JIA was not impaired. An overall low level of IL-1 beta secretion upon exposure to exogenous ATP was observed, unrelated to treatment responsiveness or disease activity. Conclusion. Two subsets of systemic-onset JIA can be identified according to patient response to IL-1 blockade. The 2 subsets appear to be characterized by some distinct clinical features. In vitro secretion of IL-1 beta and IL-18 by monocytes from patients with systemic-onset RA is not increased and is independent of both treatment outcome and disease activity.
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