A killing defect of natural killer cells as an underlying immunologic abnormality in childhood systemic lupus erythematosus.
1996
Objective. To elucidate the nature of the natural killer (NK) cell system in children with systemic lupus erythematosus (SLE), we performed phenotypic and functional studies of circulating NK cells during the course of childhood SLE. For comparison, similar examinations were undertaken in juvenile rheumatoid arthritis (JRA). Methods. Twenty-five children with SLE and 27 children with JRA were studied ; 5 of these children with SLE were examined 6 to 67 months before the overt progression to SLE. The number and cytolytic function of NK cells were determined, using flow cytometry, 51 Cr release, and single-cell cytotoxicity assays. Results. At the diagnosis of SLE, a decrease in NK cells defined as CD16+ or CD56+ was the most prominent of the numerical changes in lymphocyte subsets. In regard to cytolytic function, NK activity in children with SLE was greatly reduced at diagnosis : at the single cell level, their NK cells were defective in killing and recycling abilities. Although the relative number of NK cells and their recycling capacity 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 killing capacity values were profoundly decreased in 5 children before the overt progression to SLE. Conclusion. It would appear that NK cell functional abnormality, characterized by a killing defect, is an underlying immunological abnormality during the course of childhood SLE.
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