The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis

Marco Gattorno, Alessandra Piccini, Denise Lasigliè, Sara Tassi, Giacomo Brisca, Sonia Carta, Laura Delfino, Francesca Ferlito, Maria Antonietta Pelagatti, Francesco Caroli, Antonella Buoncompagni, Stefania Viola, Anna Loy, Marina Sironi, Annunciata Vecchi, Angelo Ravelli, Alberto Martini, Anna Rubartelli

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1505-1515
Number of pages11
JournalArthritis and Rheumatism
Volume58
Issue number5
DOIs
Publication statusPublished - May 2008

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Juvenile Arthritis
Interleukin-1
Interleukin-18
Interleukin 1 Receptor Antagonist Protein
Therapeutics
Monocytes
Interleukin-1 Receptors
Toll-Like Receptors
Neutrophils
Adenosine Triphosphate
Joints
Western Blotting
Enzyme-Linked Immunosorbent Assay
Tissue Donors
Ligands

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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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 journalArticle

Gattorno, M, Piccini, A, Lasigliè, D, Tassi, S, Brisca, G, Carta, S, Delfino, L, Ferlito, F, Pelagatti, MA, Caroli, F, Buoncompagni, A, Viola, S, Loy, A, Sironi, M, Vecchi, A, Ravelli, A, Martini, A & Rubartelli, A 2008, 'The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis', Arthritis and Rheumatism, vol. 58, no. 5, pp. 1505-1515. https://doi.org/10.1002/art.23437
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. / The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. In: Arthritis and Rheumatism. 2008 ; Vol. 58, No. 5. pp. 1505-1515.
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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.",
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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.

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