Autoinflammatory diseases associated with macrophage activation syndrome

Abstract

 Macrophage activation syndrome （MAS） is defined as secondary hemophagocytic lymphohistiocytois related to rheumatic diseases. Excessive activation of immune system, and overproduction of proinflammatory cytokines play a central role in the pathogenesis of MAS. MAS is a potentially life-threating condition clinically characterized by fever, hepatosplenomegaly, cytopenia, liver injury, hyperferritinemia, coagulopathy, NK cell dysfunction, and expansion of activated macrophages with hemophagocytosis. Although MAS has been associated with most rheumatic diseases, it is most common in systemic juvenile idiopathic arthritis （s-JIA）. Chronic interleukin （IL）-18 exposure inducing overproduction of interferon-γ, suppression of IL-10 production, and secondary suppression of cytolytic function is closely associated to the development of MAS associated with s-JIA. Important role of IL-18 in the pathogenesis of MAS has been brought to attention by the discovery of genetic autoinflammatory diseases with recurrent MAS and massive elevation of serum IL-18 levels including NLRC4 gain of function, XIAP deficiency, and neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash and HLH （NOCARH） syndrome. However, only overproduction of IL-18 cannot induce MAS development. Further studies are necessary to clarify the complex pathogenesis of MAS.