title: The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1beta 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-1beta 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-1beta 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-1beta secretion upon exposure to exogenous ATP was observed, unrelated to treatment responsiveness or disease activity.
  
  
  CONCLUSIONS
  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-1beta and IL-18 by monocytes from patients with systemic-onset JIA is not increased and is independent of both treatment outcome and disease activity.
authors.affiliation: G. Gaslini Institute, Genoa, Italy. marcogattorno@ospedale-gaslini.ge.it
authors.forename: Marco
authors.initials: M
authors.lastname: Gattorno
authors.forename: Alessandra
authors.initials: A
authors.lastname: Piccini
authors.forename: Denise
authors.initials: D
authors.lastname: Lasigliè
authors.forename: Sara
authors.initials: S
authors.lastname: Tassi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Brisca
authors.forename: Sonia
authors.initials: S
authors.lastname: Carta
authors.forename: Laura
authors.initials: L
authors.lastname: Delfino
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferlito
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Pelagatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Caroli
authors.forename: Antonella
authors.initials: A
authors.lastname: Buoncompagni
authors.forename: Stefania
authors.initials: S
authors.lastname: Viola
authors.forename: Anna
authors.initials: A
authors.lastname: Loy
authors.forename: Marina
authors.initials: M
authors.lastname: Sironi
authors.forename: Annunciata
authors.initials: A
authors.lastname: Vecchi
authors.forename: Angelo
authors.initials: A
authors.lastname: Ravelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Anna
authors.initials: A
authors.lastname: Rubartelli
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000145:classification* / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology / Q000627:therapeutic use*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D053583:Interleukin-1beta