CD3-(CD56 or 16)+ natural killer cell distribution in blood from healthy adults and patients with ANCA-associated vasculitis

Abstract

BackgroundCytotoxic Natural Killer (NK) cells are an important target of new drugs entering the clinics, including checkpoint inhibitors and cell-depleting therapeutic antibodies. Still, basic blood NK cell parameters are poorly defined in healthy adults and in chronic inflammatory diseases like ANCA-associated vasculitis (AAV) which may alter the distribution of lymphocytes. The aims of this study were 1) to establish reference values of NK cell counts and percentages in healthy adults; 2) to describe these parameters in AAV; and 3) to investigate whether NK cell counts and percentages may be used as activity biomarker in the care of AAV patients, as suggested by a preceding study.MethodsCD3-(CD56 or 16)+ NK cell counts and percentages were determined in 120 healthy adults. Lymphocyte subset data from two German vasculitis centers were retrospectively analyzed (in total 407 measurements, including 201/49/157 measurements from 64/16/39 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), respectively).ResultsCD3-(CD56 or 16)+ NK cell counts and percentages in healthy adults were highly variable, not Gaussian distributed and independent of age and sex. NK cell percentages ranged from 1.9 to 37.9% of lymphocytes, and were significantly more dispersed in AAV (0.3 to 57.6%). We further found that NK cell counts and percentages were different between AAV entities. However, during active disease, NK cell counts were consistently low in each AAV entity compared to healthy donors. NK cells were especially low in inactive EGPA. In 18% of EGPA patients we observed percentages of 1% or below which may be interpreted as temporary NK cell deficiency. Findings on differences between active and inactive GPA were discrepant between vasculitis centers.ConclusionsNK cell counts and percentages in blood are highly variable. This variability is further enhanced in systemic inflammatory diseases, and includes patients with temporary NK cell deficiency, in particular in EGPA. NK cell counts and percentages can presently not be recommended as biomarker in clinical care of AAV patients.