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Abstract Number: 142

Neutrophils and monocytes in the early inflammatory cascade of systemic onset Juvenile Idiopathic Arthritis

Nienke M. ter Haar1, Wilco de Jager2, Rianne C. Scholman1, Jenny Meerding1, Bas Vastert3,4 and Sytze de Roock4, 1Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands, 2Dept Immunology, UMC Utrecht, Utrecht, Netherlands, 3Division of Pediatric Rheumatology, University Medical Center Utrecht, Utrecht, Netherlands, 4Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands

Meeting: 2017 Pediatric Rheumatology Symposium

Keywords: Autoinflammatory Disease, IL-1/IL-18, mechanisms and pediatric rheumatology

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Session Information

Date: Thursday, May 18, 2017

Session Title: Genetics and Pathogenesis Poster Session

Session Type: Abstract Submissions

Session Time: 5:30PM-7:00PM

Background/Purpose:

Systemic onset Juvenile Idiopathic Artritis (sJIA) is an acquired systemic autoinflammatory disease characterized by spiking fever, arthritis and skin rash. Patients display high inflammatory parameters and high circulating levels of interleukin(IL)-18 and phagocyte-derived S100-proteins. The role of specific innate immune cells is still to be unravelled. Here, we aimed to dissect the role of monocytes and neutrophils in the early inflammatory cascade of sJIA.

Methods:  We determined neutrophil activation ex vivo (cell surface markers) and after stimulation (ROS-production and degranulation) of sJIA patients with active disease or inactive disease, compared to healthy donors (HDs). To investigate the role of monocytes, we stimulated peripheral blood derived mononuclear cells (PBMC) from active and inactive sJIA patients and HDs with TLR4-stimulating S100-proteins or other TLR-ligands. Cytokine levels in serum and supernatant were measured by multiplex immunoassay.

Results:  At disease onset, 37/47 sJIA patients had elevated neutrophil counts. Neutrophil-specific proteins elastase and neutrophil collagenase were significantly elevated in onset sJIA, compared to inactive sJIA. Neutrophils from active sJIA patients showed an activated phenotype, reflected by higher ex vivo expression of FC-gamma receptors (CD32, CD64) and degranulation markers (CD35, CD66b) and enhanced ROS-production and degranulation after stimulation, compared to HDs. Neutrophil phenotype normalized when patients had inactive disease. In contrast to the hyperactivated status of neutrophils in active sJIA, PBMC from active sJIA produced less IL-1beta, IL-18, IL-6 and TNF-alpha upon TLR-stimulation compared to inactive patients or HDs.

Conclusion:  We show here that in active sJIA, neutrophils but not monocytes seem to be crucial in driving the systemic inflammatory response. Neutrophils show an activated phenotype, while monocytes display tolerogenic characteristics, possibly as a compensation to the high S100-levels in vivo. RNA-sequencing of FACS-sorted monocytes and neutrophils of sJIA patients is currently undertaken and will reveal pathways involved in the phenotype of these cells.


Disclosure: N. M. ter Haar, None; W. de Jager, None; R. C. Scholman, None; J. Meerding, None; B. Vastert, None; S. de Roock, None.

To cite this abstract in AMA style:

ter Haar NM, de Jager W, Scholman RC, Meerding J, Vastert B, de Roock S. Neutrophils and monocytes in the early inflammatory cascade of systemic onset Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/neutrophils-and-monocytes-in-the-early-inflammatory-cascade-of-systemic-onset-juvenile-idiopathic-arthritis/. Accessed January 31, 2023.
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