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.

Peripheral blood natural killer cells activation status determined by CD69 upregulation predicts implantation outcome in IVF.

PROBLEM: NK lymphocytes play critical yet poorly defined role in implantation and during development in early pregnancy. METHODS OF STUDY: Recently, we showed that the proportion of NK that expressed CD69⁺ after incubation with K562 (CD69(stim)) cells reflected the NK population excitation potential. In the present study, we investigate the significance of NK activation levels in predicting embryo implantation. RESULTS: A qualitative analysis of values distribution in two groups showed that 25/33 (75.8%) women who became pregnant had CD69(stim) levels that were >30 but <60% (conditionally normal zone). In contrast, CD69(stim) levels in patients who failed to become pregnant were either elevated, as in 10/51 (19.6%), or reduced, as in 20/51 (39.2%) of the patients. Accentuated CD69(stim) levels were predictive for implantation failure, extremely significant for decreased (OR 6.9, p=0.0004) and not quite significant for increased CD69(stim) levels (OR 3.9, p=0.062). Accordingly, conditionally normal CD69(stim) levels were favourable for implantation (OR 4.46, p=0.0032). CONCLUSION: We confirm that actual peripheral blood natural killer cells activation status have an influence on embryo implantation. We showed that exactly normal NK cell activity predicting successful implantation.