The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis.
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.
Gattorno
Marco
M
G. Gaslini Institute, Genoa, Italy. marcogattorno@ospedale-gaslini.ge.it
Piccini
Alessandra
A
Lasigliè
Denise
D
Tassi
Sara
S
Brisca
Giacomo
G
Carta
Sonia
S
Delfino
Laura
L
Ferlito
Francesca
F
Pelagatti
Maria Antonietta
MA
Caroli
Francesco
F
Buoncompagni
Antonella
A
Viola
Stefania
S
Loy
Anna
A
Sironi
Marina
M
Vecchi
Annunciata
A
Ravelli
Angelo
A
Martini
Alberto
A
Rubartelli
Anna
A
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
D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D053583:Interleukin-1beta