High NK cell activity in recurrent miscarriage: what are we really measuring?

BACKGROUND: Several studies have shown that women with unexplained recurrent miscarriage (RM) have increased numbers and activity of peripheral blood NK cells and that elevated levels of these cells predict subsequent miscarriages in women with RM. Because catecholamines rapidly mobilize NK cells into the circulation, such increases may not reflect a steady state of overactive immunity but may result from a transient increase in the number of NK cells because of the stress associated with blood withdrawal. METHODS: Blood was drawn from 22 controls and 38 RM patients immediately after vein cannulation, and again 20 min later. The percentage of NK cells within lymphocytes, their concentration per microlitre of blood and their activity were assessed. RESULTS: All three indices of NK cells did not change in the controls across the two samples. However, women with RM had elevated levels in all three NK indices in the first blood sample, but these levels declined to values similar to those seen in the controls. This decline was mainly observed in primary aborters whose NK activity was highest in the first blood withdrawal. Accordingly, there was a high correlation between the magnitude of the decline and the initial NK cell indices in women with RM. The change in activity highly correlated with the change in the concentration of NK cells. CONCLUSION: The increased NK number and activity previously observed in RM patients may result from a transient stress response at the time of blood withdrawal. Patients with primary RM may be characterized by exaggerated acute stress responses in other circumstances.