Macrophage activation syndrome in rheumatic disease: what is the role of the antigen presenting cell?

Macrophage Activation Syndrome (MAS), alternatively referred to as secondary hemophagocytic lymphohistiocytosis (HLH), is a complication of many rheumatic diseases, most commonly Systemic Juvenile Idiopathic Arthritis (SJIA). MAS consists of a fulminant picture of pan-cytopenia, hectic high fevers, hepatosplenomegaly, lymphadenopathy, rash, and central nervous systemic inflammation. It can arise from genetic defects in the cytotoxic effector response of CD8+ T-cells, resulting in an inability to terminate antigen presentation, which in turn leads to uncontrolled immune activation. However, in the case of most rheumatic diseases, no such defect in cytotoxic killing is present. Little is known about what the contributions from the antigen presenting cells are in the pathogenesis of MAS. In fact, macrophages may be playing a regulatory, anti-inflammatory in MAS. We review the proposed pathogenesis of MAS/HLH, what role macrophages may play in the disease, and the relationship of MAS to its most common associated rheumatic disease, SJIA.