Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome

Author:

Weiss Eric S.1,Girard-Guyonvarc’h Charlotte2,Holzinger Dirk34,de Jesus Adriana A.5,Tariq Zeshan6,Picarsic Jennifer7ORCID,Schiffrin Eduardo J.8,Foell Dirk3,Grom Alexei A.9,Ammann Sandra10,Ehl Stephan10,Hoshino Tomoaki11,Goldbach-Mansky Raphaela5,Gabay Cem2ORCID,Canna Scott W.1ORCID

Affiliation:

1. RK Mellon Institute, Children’s Hospital of Pittsburgh of UPMC/University of Pittsburgh, Pittsburgh, PA;

2. Division of Rheumatology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland;

3. Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Muenster, Muenster, Germany;

4. Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany;

5. Translational Autoinflammatory Diseases Studies, National Institute of Allergy and Infectious Diseases, and

6. Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD;

7. Department of Pathology, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA;

8. AB2Bio, Ltd., Lausanne, Switzerland;

9. Pediatric Rheumatology, Cincinnati Children’s Hospital, Cincinnati, OH;

10. Center for Chronic Immunodeficiency, Faculty of Medicine, University of Freiburg, Freiburg, Germany; and

11. Division of Respirology, Neurology, and Rheumatology, Kurume University School of Medicine, Kurume, Japan

Abstract

Key Points IL-18 distinguishes susceptibility to MAS amongst hyperferritinemic and autoinflammatory diseases. Excess IL-18 in NLRC4 gain-of-function mice derives from intestinal epithelia, and free IL-18 promotes experimental MAS.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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