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, Matteo; Caroli, Francesco; Buoncompagni, Antonella; Viola, Stefania; Loy, Anna; Sironi, Marina; Vecchi, Annunciata; Ravelli, Angelo; Martini, Alberto; Rubartelli, Anna

doi:10.1002/art.23437

Cited by 356 publications

(310 citation statements)

References 38 publications

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“…The inhibition of IL-1 or IL-6 is highly efficacious in many patients with s-JIA, yielding improvements in both systemic symptoms and arthritis [52,53]. Furthermore, recent studies demonstrated the identification of two subgroups of s-JIA with distinct clinical features [19,52,53]. In the present study, we demonstrated the similar existence of two subgroups of patients with AOSD and certain distinct clinical features that could be distinguished based on IL-6 and IL-18 levels.…”

Section: Discussionsupporting

confidence: 72%

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Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

Inoue

Shimizu

Tsunoda

et al. 2016

Clinical Immunology

124

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To compare pro-inflammatory cytokine profiles and kinetics in patients with adult-onset Still's disease (AOSD) to those in patients with systemic juvenile idiopathic arthritis (s-JIA), we analyzed serum cytokine concentrations in 33 patients with AOSD and 77 patients with s-JIA and compared them with clinical features. Patients with AOSD and s-JIA shared a common cytokine profile pattern of a significant increase in IL-18. Patients with AOSD were classified into two subgroups based on serum IL-6 and IL-18 levels. The number of patients with arthritis was significantly higher in the IL-6-dominant subgroup. The cytokine patterns associated with s-JIA and AOSD share common features, such as a significant and predominant increase in IL-18. Distinct IL-6-and IL-18-based cytokine profiles might be responsible for distinct clinical manifestations. The presence of two distinct subgroups in patients with both diseases further supports the view that s-JIA and AOSD share a disease category.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

Inoue

Shimizu

Tsunoda

et al. 2016

Clinical Immunology

124

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“…Further support for the role of IL-1 in systemiconset disease in children comes from a recent analysis in which complete responders to anakinra in patients with this condition appear to be characterized by the presence of distinct clinical features [36].…”

Section: Discussionmentioning

confidence: 99%

Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

et al. 2008

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This study assessed the safety and preliminary efficacy of the interleukin-1 receptor antagonist anakinra in patients with polyarticular-course juvenile rheumatoid arthritis (JRA). Eighty-six patients entered a 12-week open-label run-in phase (1 mg/kg anakinra daily, ≤100 mg/day). Fifty responders were randomized to anakinra or placebo in a 16-week blinded phase, followed by a 12-month open-label extension (N=44). Due to low enrollment, the primary endpoint was changed from efficacy to safety. The incidence and nature of adverse events were similar across all study phases, with the exception of injection site reactions, which were mild to moderate and decreased with time. Anakinra produced a nonsignificant (P=0.11) reduction in disease flares compared with placebo. When normalized to 1 mg/kg dose, anakinra plasma concentrations were similar to values in adult patients with rheumatoid arthritis. These results indicate that anakinra 1 mg/kg once daily (≤100 mg/day) is safe and well tolerated in patients with JRA.

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“…inflammatory features that tend to respond to anti-IL-1 therapies (6) and others following an arthritis-predominant disease course that may ultimately lead to chronic, destructive, treatment-refractory arthritis (7,8).…”

Section: Significancementioning

confidence: 99%

HLA-DRB111*and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

Ombrello¹,

Remmers²,

Tachmazidou³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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146

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Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10−17, odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10−5, OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10−16, OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11—HLA-DQA1*05—HLA-DQB1*03 haplotype [6.4 × 10−17, OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.

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

Cited by 356 publications

References 38 publications

Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

HLA-DRB111*and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

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

Cited by 356 publications

References 38 publications

Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis

Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

HLA-DRB1*11and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

Contact Info

Product

Resources

About

HLA-DRB111*and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis