Abstract
Objective. To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1β and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA). Methods. Twenty-two patients with systemic-onset 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-1β 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 1 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-1β 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-1β 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-1β and IL-18 by monocytes from patients with systemic-onset JIA is not increased and is independent of both treatment outcome and disease activity.
| Original language | English |
|---|---|
| Pages (from-to) | 1505-1515 |
| Number of pages | 11 |
| Journal | Arthritis and Rheumatism |
| Volume | 58 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2008 |
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ASJC Scopus subject areas
- Immunology
- Rheumatology
Cite this
The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. / Gattorno, Marco; Piccini, Alessandra; Lasigliè, Denise; Tassi, Sara; Brisca, Giacomo; Carta, Sonia; Delfino, Laura; Ferlito, Francesca; Pelagatti, Maria Antonietta; Caroli, Francesco; Buoncompagni, Antonella; Viola, Stefania; Loy, Anna; Sironi, Marina; Vecchi, Annunciata; Ravelli, Angelo; Martini, Alberto; Rubartelli, Anna.
In: Arthritis and Rheumatism, Vol. 58, No. 5, 05.2008, p. 1505-1515.Research output: Contribution to journal › Article
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TY - JOUR
T1 - The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis
AU - Gattorno, Marco
AU - Piccini, Alessandra
AU - Lasigliè, Denise
AU - Tassi, Sara
AU - Brisca, Giacomo
AU - Carta, Sonia
AU - Delfino, Laura
AU - Ferlito, Francesca
AU - Pelagatti, Maria Antonietta
AU - Caroli, Francesco
AU - Buoncompagni, Antonella
AU - Viola, Stefania
AU - Loy, Anna
AU - Sironi, Marina
AU - Vecchi, Annunciata
AU - Ravelli, Angelo
AU - Martini, Alberto
AU - Rubartelli, Anna
PY - 2008/5
Y1 - 2008/5
N2 - Objective. To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1β and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA). Methods. Twenty-two patients with systemic-onset 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-1β 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 1 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-1β 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-1β 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-1β and IL-18 by monocytes from patients with systemic-onset JIA is not increased and is independent of both treatment outcome and disease activity.
AB - Objective. To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1β and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA). Methods. Twenty-two patients with systemic-onset 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-1β 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 1 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-1β 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-1β 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-1β and IL-18 by monocytes from patients with systemic-onset JIA is not increased and is independent of both treatment outcome and disease activity.
UR - http://www.scopus.com/inward/record.url?scp=43949116263&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43949116263&partnerID=8YFLogxK
U2 - 10.1002/art.23437
DO - 10.1002/art.23437
M3 - Article
C2 - 18438814
AN - SCOPUS:43949116263
VL - 58
SP - 1505
EP - 1515
JO - Arthritis care and research : the official journal of the Arthritis Health Professions Association
JF - Arthritis care and research : the official journal of the Arthritis Health Professions Association
SN - 0893-7524
IS - 5
ER -