Abnormal natural killer cell activity in systemic lupus erythematosus: An intrinsic defect in the lytic event

The natural killer (NK) cell activity in fifteen systemic lupus erythematosus (SLE) patients was investigated by employing 51-chromium (⁵¹Cr) release microcytotoxicity and single cell cytotoxicity assays against K562 target cells. Although the SLE patients as a group had depressed NK function in the ⁵¹Cr-release assay compared to normal subjects (p < 0.005), those with clinically active disease displayed the greatest impairment in this activity (p < 0.001). Active SLE patients were deficient in overall NK activity (Vmax) (p < 0.005) but had normal percentages of potentially cytotoxic target binding cells (TBC). These TBC, however, were unable to normally kill bound target cells (p < 0.01), which is indicative of a deficiency of 'active' NK cells (p < 0.005). Those NK cells with intact cytotoxic capabilities could 'recycle' and repeat the lytic sequence normally. Exposure of normal lymphocytes to SLE sera did not impair any phase of NK function. These studies indicate that defective NK activity in SLE is secondary to an abnormality in the lytic event itself and is not due to a deficiency of NK cells, an abnormality in target binding, or an inability of NK cells to lyse mutiple targets. Additionally, serum factors do not appear to play a major etiologic role in the cytotoxic abnormalities of these patients.