A KILLING DEFECT OF NATURAL-KILLER-CELLS AS AN UNDERLYING IMMUNOLOGICAL ABNORMALITY IN CHILDHOOD SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. To elucidate the nature of the natural killer (NK) cell sys tem in children with systemic lupus erythematosus (SLE), we performed phenotypic and functional studies of circulating NK cells during the c ourse of childhood SLE. For comparison, similar examinations were unde rtaken in juvenile rheumatoid arthritis (JRA). Methods. Twenty-five ch ildren with SLE and 27 children with JRA were studied; 5 of these chil dren with SLE were examined 6 to 67 months before the overt progressio n to SLE. The number and cytolytic function of NK cells were determine d, using flow cytometry, Cr-51 release, and single-cell cytotoxicity a ssays, Results, At the diagnosis of SLE, a decrease in NK cells define d as CD16+ or CD56+ was the most prominent of the numerical changes in lymphocyte subsets. In regard to cytolytic function, NK activity in c hildren with SLE was greatly reduced at diagnosis: at the single cell level, their NK cells were defective in killing and recycling abilitie s. Although the relative number of NK cells and their recycling capaci ty returned to normal with the improvement of active SLE, the killing defect persisted during the inactive phase; there was no persistent NK cell abnormality in JRA. Reduced NK activity due to a killing defect was demonstrable early in the course of SLE: the NK activity and killi ng capacity values were profoundly decreased in 5 children before the overt progression to SLE. Conclusion. It would appear that NK cell fun ctional abnormality, characterized by a killing defect, is an underlyi ng immunological abnormality during the course of childhood SLE.