Abstract

of the clinical manifestations of NLRC4 hyperactivity in September 2014. Since that time, we have been continuously working to link this genotypic observation with the associated phenotypes of early-onset enterocolitis, Macrophage Activation Syndrome (MAS), and chronically elevated serum IL-18. We have continued to identify that MAS is uniquely marked by elevated IL-18, and this IL-18 is bioactive. We have further been measuring the natural antagonist of IL-18, the IL-18 binding protein IL-18BP), and find this to be highly elevated only during highly active disease in both MAS and in the related condition Hemophagocytic Lymphohistiocytosis (HLH). We find that IL-18BP is not necessarily induced by IL-18 directly, but correlates with other cytokines known to be induced by Interferon gamma. We anticipate publication of the first MAS patient treated with recombinant IL-18BP within the next month, and we are actively working to develop a small, multi-center study to follow up on this observation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAR041202-03
Application #
9359808
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
Arthritis, Musculoskeletal, Skin Dis
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Canna, Scott W; Nigrovic, Peter A (2016) Editorial: 21st Century Storm Chasers: Defining Macrophage Activation Syndrome. Arthritis Rheumatol 68:557-60
de Jesus, Adriana Almeida; Canna, Scott W; Liu, Yin et al. (2015) Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu Rev Immunol 33:823-74
Canna, Scott W; Goldbach-Mansky, Raphaela (2015) New monogenic autoinflammatory diseases--a clinical overview. Semin Immunopathol 37:387-94
Canna, Scott W; de Jesus, Adriana A; Gouni, Sushanth et al. (2014) An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet 46:1140-6
Canna, Scott W; Costa-Reis, Patrícia; Bernal, William E et al. (2014) Brief report: alternative activation of laser-captured murine hemophagocytes. Arthritis Rheumatol 66:1666-71
Canna, Scott W (2014) Editorial: interferon-?: friend or foe in systemic juvenile idiopathic arthritis and adult-onset Still's Disease? Arthritis Rheumatol 66:1072-6
Canna, Scott W; Chauvin, Nancy A; Burnham, Jon M (2013) A 17 year old with isolated proximal tibiofibular joint arthritis. Pediatr Rheumatol Online J 11:1
Canna, Scott W; Wrobel, Julia; Chu, Niansheng et al. (2013) Interferon-? mediates anemia but is dispensable for fulminant toll-like receptor 9-induced macrophage activation syndrome and hemophagocytosis in mice. Arthritis Rheum 65:1764-75