Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome

Objectives To assess natural killer (NK) and cytotoxic functions in patients with systemic-onset juvenile rheumatoid arthrithis (soJRA) complicated by macrophage activation syndrome (MAS). Methods NK cells (CD56+/TCRaP-), NK T cells (CD56+/TCRalphabeta+) and CD8+ cells were assessed for perforin expression by flow cytometry. NK cytotoxic activity was measured after coincubation of mononuclear cells with an NK-sensitive K562 cell line. Results Two major patterns of immunologic abnormalities were detected. Four of 7 patients had decreased NK activity, low NK cell numbers, and mildly increased levels of perforin expression in CDS+ and CD56+ cytotoxic cells. Three remaining patients with MAS, however, had decreased NK activity associated with low levels of perforin expression in all cytotoxic cell populations, a pattern indistinguishable from that in carriers of perforin-deficient familial hemophagocytic lymphohistiocytosis. Remarkably, two of these patients had previous episodes of MAS. Conclusions NK dysfunction is an immunologic abnormality common to both familial hemophagocytic lymphohistiocytosis and MAS of soJRA. The extent of NK cell abnormalities in soJRA needs to be further investigated.