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Abstract Number: 1950

Elevated Serum Gasdermin D N-terminal Implicates Macrophage Pyroptosis in Adult-onset Still’s Disease and Systemic Juvenile Idiopathic Arthritis

Hideto Nagai1, Yohei Kirino2, Hiroto Nakano3, Yosuke Kunishita1 and Michael Ombrello4, 1Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan, 2Yokohama City University Graduate School of Medicine, Yokohama, Japan, 3NIAMS, NIH, Bethesda, 4Translational Genetics and Genomics Unit, NIAMS, NIH, Bethesda, MD

Meeting: ACR Convergence 2020

Keywords: Autoinflammatory diseases, Cell Death, Juvenile idiopathic arthritis, Still's disease

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Session Information

Date: Monday, November 9, 2020

Session Title: Cytokines & Cell Trafficking (1948–1952)

Session Type: Abstract Session

Session Time: 3:00PM-3:50PM

Background/Purpose: Elevation of serum IL-18 in adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) suggests involvement of one or more inflammasome in these diseases, but their pathogenesis is still uncertain. We aimed to elucidate the auto-inflammatory mechanisms in AOSD and sJIA.

Methods: Patients with AOSD, sJIA, hemophagocytic lymphohistiocytsis (HLH), and Behçet’s disease followed at Yokohama City University (YCU), or U.S. National Institutes of Health (NIH) were included in the study. Disease activity was evaluated by the modified Pouchot score. Ferritin and N-terminal gasdermin D (a pore-forming protein playing central roles in inflammasome-mediated inflammation) levels in serum and culture supernatant were measured by ELISA. Primary monocytes (Mo) were stimulated with GM-CSF or M-CSF and differentiated into M1 macrophages (Mφ) or M2Mφ, respectively. The number of Mo/Mφ and their viability were monitored over time.

Results: Patients with active AOSD and sJIA had increased levels of serum gasdermin D N-terminal, which correlated with serum ferritin and IL-18 levels. Mo-derived Mφ from active AOSD patients showed reduced cell viability and increased cell death. The number of cultured Mφ cells on day nine was negatively correlated with the serum ferritin and gasdermin D levels. Higher ferritin and gasdermin D levels were observed in the M1Mφ culture supernatant of active AOSD patients.

Conclusion: Elevation of serum gasdermin D N-terminal and increased Mφ cell death suggests that Mφ pyroptosis is associated with AOSD and sJIA.


Disclosure: H. Nagai, None; Y. Kirino, None; H. Nakano, None; Y. Kunishita, None; M. Ombrello, None.

To cite this abstract in AMA style:

Nagai H, Kirino Y, Nakano H, Kunishita Y, Ombrello M. Elevated Serum Gasdermin D N-terminal Implicates Macrophage Pyroptosis in Adult-onset Still’s Disease and Systemic Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/elevated-serum-gasdermin-d-n-terminal-implicates-macrophage-pyroptosis-in-adult-onset-stills-disease-and-systemic-juvenile-idiopathic-arthritis/. Accessed April 13, 2021.
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