Reversal of Sepsis‐Like Features of Neutrophils by Interleukin‐1 Blockade in Patients With Systemic‐Onset Juvenile Idiopathic Arthritis

Haar, Nienke Ter; Tak, Tamar; Mokrý, Michal; Scholman, Rianne C.; Meerding, Jenny; Jager, Wilco de; Verwoerd, Anouk; Foell, Dirk; Vogl, Thomas; Roth, Johannes; Leliefeld, Pieter H. C.; Loosdregt, Jorg van; Koenderman, Leo; Vastert, Sebastiaan J.; Roock, Sytze de

doi:10.1002/art.40442

Cited by 38 publications

(49 citation statements)

References 52 publications

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“…Our single‐center, prospective cohort study may provide a first step toward personalized medicine for systemic JIA. The predictive value of neutrophil counts for response to rIL‐1Ra supports findings from a previous study of our cohort, which provided evidence that neutrophils have an important role in the early inflammatory phase of systemic JIA . Our findings suggest that, especially in the early phase of systemic JIA, which is characterized by pronounced innate immune activation and neutrophilia, patients may be highly responsive to IL‐1 blockade, indicating the existence of a window of opportunity.…”

Section: Discussionsupporting

confidence: 88%

Treatment to Target Using Recombinant Interleukin‐1 Receptor Antagonist as First‐Line Monotherapy in New‐Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five‐Year Follow‐Up Study

Haar

Dijkhuizen

Swart

et al. 2019

Arthritis & Rheumatology

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136

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Objective Systemic juvenile idiopathic arthritis (JIA) is a multifactorial autoinflammatory disease with a historically poor prognosis. With current treatment regimens, approximately half of patients still experience active disease after 1 year of therapy. This study was undertaken to evaluate a treat‐to‐target approach using recombinant interleukin‐1 receptor antagonist (rIL‐1Ra; anakinra) as first‐line monotherapy to achieve early inactive disease and prevent damage. Methods In this single‐center, prospective study, patients with new‐onset systemic JIA with an unsatisfactory response to nonsteroidal antiinflammatory drugs received rIL‐1Ra monotherapy according to a treat‐to‐target strategy. Patients with an incomplete response to 2 mg/kg rIL‐1Ra subsequently received 4 mg/kg rIL‐1Ra or additional prednisolone, or switched to alternative therapy. For patients in whom inactive disease was achieved, rIL‐1Ra was tapered after 3 months and subsequently stopped. Results Forty‐two patients, including 12 who had no arthritis at disease onset, were followed up for a median of 5.8 years. The median time to achieve inactive disease was 33 days. At 1 year, 76% had inactive disease, and 52% had inactive disease while not receiving medication. High neutrophil counts at baseline and a complete response after 1 month of rIL‐1Ra were highly associated with inactive disease at 1 year. After 5 years of follow‐up, 96% of the patients included had inactive disease, and 75% had inactive disease while not receiving medication. Articular or extraarticular damage was reported in <5%, and only 33% of the patients received glucocorticoids. Treatment with rIL‐1Ra was equally effective in systemic JIA patients without arthritis at disease onset. Conclusion Treatment to target, starting with first‐line, short‐course monotherapy with rIL‐1Ra, is a highly efficacious strategy to induce and sustain inactive disease and to prevent disease‐ and glucocorticoid‐related damage in systemic JIA.

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Section: Discussionsupporting

confidence: 88%

Treatment to Target Using Recombinant Interleukin‐1 Receptor Antagonist as First‐Line Monotherapy in New‐Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five‐Year Follow‐Up Study

Haar

Dijkhuizen

Swart

et al. 2019

Arthritis & Rheumatology

Self Cite

136

110

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“…In human experimental endotoxemia, peripheral neutrophils exhibit a functional heterogeneity and different degrees of priming ( 122 ). Similar variations in neutrophil phenotypes are seen in the peripheral blood of patients during severe inflammation ( 137 ). A large number of immature or banded cells, suppressive neutrophils, myeloid-derived suppressor cells, and neutrophil progenitor cells can be detected ( 119 ).…”

Section: The Importance Of Neutrophils In Inflammatory Complications supporting

confidence: 58%

Update on Neutrophil Function in Severe Inflammation

et al. 2018

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Neutrophils are main players in the effector phase of the host defense against micro-organisms and have a major role in the innate immune response. Neutrophils show phenotypic heterogeneity and functional flexibility, which highlight their importance in regulation of immune function. However, neutrophils can play a dual role and besides their antimicrobial function, deregulation of neutrophils and their hyperactivity can lead to tissue damage in severe inflammation or trauma. Neutrophils also have an important role in the modulation of the immune system in response to severe injury and trauma. In this review we will provide an overview of the current understanding of neutrophil subpopulations and their function during and post-infection and discuss the possible mechanisms of immune modulation by neutrophils in severe inflammation.

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“…Ter Haar et al showed that neutrophils played an important role in the early inflammatory phase of sJIA, and the number and inflammatory activity of neutrophils were highly sensitive to the blockade of IL-1 signaling [ 105 ]. To examine activated neutrophil subsets, Brown et al isolated neutrophils from children with active sJIA or clinically inactive disease (CID) [ 106 ].…”

Section: Transcriptome Study Of Jiamentioning

confidence: 99%

The Multi-Omics Architecture of Juvenile Idiopathic Arthritis

Hou

Zhang

et al. 2020

Cells

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Juvenile idiopathic arthritis (JIA) is highly heterogeneous in terms of etiology and clinical presentation with ambiguity in JIA classification. The advance of high-throughput omics technologies in recent years has gained us significant knowledge about the molecular mechanisms of JIA. Besides a minor proportion of JIA cases as monogenic, most JIA cases are polygenic disease caused by autoimmune mechanisms. A number of HLA alleles (including both HLA class I and class II genes), and 23 non-HLA genetic loci have been identified of association with different JIA subtypes. Omics technologies, i.e., transcriptome profiling and epigenomic analysis, contributed significant knowledge on the molecular mechanisms of JIA in addition to the genetic approach. New molecular knowledge on different JIA subtypes enables us to reconsider the JIA classification, but also highlights novel therapeutic targets to develop a cure for the devastating JIA.

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Reversal of Sepsis‐Like Features of Neutrophils by Interleukin‐1 Blockade in Patients With Systemic‐Onset Juvenile Idiopathic Arthritis

Cited by 38 publications

References 52 publications

Treatment to Target Using Recombinant Interleukin‐1 Receptor Antagonist as First‐Line Monotherapy in New‐Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five‐Year Follow‐Up Study

Treatment to Target Using Recombinant Interleukin‐1 Receptor Antagonist as First‐Line Monotherapy in New‐Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five‐Year Follow‐Up Study

Update on Neutrophil Function in Severe Inflammation

The Multi-Omics Architecture of Juvenile Idiopathic Arthritis

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