Natural killer cell dysfunction - A common pathway in systemic-onset juvenile rheumatoid arthritis, macrophage activation syndrome, and hemophagocytic lymphohistiocytosis?

The analysis of pathophysiologic similarities between HLH and MAS leads to the hypothesis that impaired cytotoxic functions and the lack of an immunoregulatory role of NK cells are relevant to the development of both syndromes. It appears likely that an intrinsic cytolytic defect is responsible for the failure to down-regulate cellular immune responses triggered by either infection or some other environmental factors. Furthermore, profound NK dysfunction may be a feature that distinguishes systemic JRA from other clinical forms of JRA as well as other rheumatic conditions. If this hypothesis were proven, it would explain the increased incidence of MAS in patients with systemic-onset JRA and provide a basis for further mechanistic studies of MAS and HLH. Both conditions are rare; therefore, cooperative efforts from pediatric rheumatologists in the US and around the world will be necessary to better understand the nature of MAS and its relationship to other HLH syndromes.