Natural killer frequency determines natural killer cytotoxicity directly in accentuated zones and indirectly in “moderate-to-normal frequency” segment

Natural killer (NK) frequency and NK cytotoxicity (NKc) are key determining factors of a clinical outcome. In our previous study, we showed the prognostic clinical significance of immune parameters when they are beyond the optimal range (accentuated). In this study, we attempted to explain the disparity of accentuated but physiologically and immunologically normal NK parameters that might serve as negative clinical prognostics indications of failed pregnancies. We have analyzed NK%, NKc levels, and their reciprocal correlation in 2,804 patients with reproductive failures.

In the entire clinical population, NK% correlates with NKc. Interestingly, we found this relationship to be strongly dependent on NK level’s status. NK%-NKc correlation was the strongest (r = 0.2021, p < 0.0001) in a patient group with high NK% (> 17.5%). Patients with NK% between 15-17.5% manifested lower but still significant correlation NK%-NKc (r = 0.1213, p = 0.0155). Additionally, significant correlation (r = 0.2689, p < < 0.0001) between NK% and NKc was observed in a group of patients with NK levels < 7% (1.7-7%). While patients’ groups with NK% (7-15%) did not reveal NK%-NKc association.

This led us to hypothesize that the qualitative-quantitative status of NK population is responsible for their cytotoxic activity. Consistent with our hypothesis, the “balanced zone” NK% is tightly controlled, and thus does not correlate directly with NKc. In contrast, the “accentuated zones” of NK% escape this control and directly affecting NKc. Demonstrated phenomena supports our idea about the clinical significance of immune accentuation and explains its novel physiological role.