A ROLE FOR NATURAL-KILLER-CELLS IN THE IMMUNOPATHOGENESIS OF MULTIPLE-SCLEROSIS

Seventeen relapsing-remitting (R/R) multiple sclerosis (MS) patients a nd age/sex matched controls were studied every 6 weeks for 2 years. Di sease activity, determined both clinically and by serial MRI, was corr elated with natural killer (NK) cell functional activity (FA) and phen otype. Mean NK cell FA is significantly lower rn MS patients, compared to controls (P < 0.001), while variability around the means is signif icantly greater(P < 0.01). The spectrum of mean NK cell FA, observed i n the patient cohort, along with cyclical nature of the FA and phenoty pe over time, observed in both patients and controls, may begin to exp lain the discrepant results reported in previous studies. In R/R MS, t here is a significant correlation between reductions (valleys) in NK c ell FA and the development of active lesions on MRI, new (P < 0.001) o r enlarging (P = 0.05). More importantly, a significant number of acti ve lesions, new (P = 0.01) and enlarging(P = 0.02), are preceded by a reduction in NK cell FA. The correlation between the onset of clinical attacks and valleys of NK cell FA is also significant(P = 0.002). Whe n taken together, the results suggest that reductions (valleys) in NK cell FA represent periods of susceptibility for the development of act ive lesions on MRI and clinical attacks. A significant positive correl ation is also identified between mean NK cell FA for each R/R MS patie nt and total number of active MRI lesions developed by that patient ov er the 2 years (P = 0.001). The results would suggest that R/R MS pati ents with a higher mean NK cell FA are at greater risk for the develop ment of active lesions. These results support the proposal that NK cel ls may play a role in the immunopathogenesis of R/R MS. (C) 1998 Elsev ier Science B.V. All rights reserved.