Inflammatory consequences of NLRC4 dysregulation

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

Investigators

Linked publications, trials & patents

Abstract

We published the first description 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.