Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3-/CD56+16+) in umbilical cord blood than those without pre-eclampsia.
OBJECTIVE
Maternal endothelial dysfunction and intravascular inflammation have been implicated in the mechanisms of disease responsible for the clinical syndrome of pre-eclampsia. Recently, the activation of the innate limb of the immune response (neutrophils and monocytes) in the fetal circulation has been reported in neonates born to mothers with pre-eclampsia. Natural killer (NK) cells are identified morphologically as a subpopulation of lymphocytes, but functionally as one component of the innate immune system. NK cells participate in the control of viral or bacterial infection, regulation of hematopoiesis, production of cytokines and cytotoxicity of neoplastic cells. Accumulating evidence suggests that the innate system is required for mounting an adequate adaptive response. NK cells, originally defined as effector cells of the innate immune system, may also play a role as regulatory cells for the adaptive immune system. This study was designed to determine the proportion of the NK cell subset of lymphocytes in umbilical cord blood of neonates born to mothers with and without pre-eclampsia.


METHODS
A cross-sectional study including neonates of mothers with (n = 48) and those without pre-eclampsia (control group) (n = 72) was conducted. Pre-eclampsia was diagnosed in the presence of hypertension and proteinuria. The control group consisted of neonates (premature and term) with no evidence of acute inflammation within the extraplacental membranes (chorioamnionitis). Umbilical cord blood was collected at the time of delivery, and assayed using monoclonal antibodies for selective cluster differentiation (CD) antigens in order to determine the proportion of NK cells as a percentage of total lymphocytes. The immunophenotypic characteristic was determined using flow cytometry, and NK cells were identified by positivity of CD16 and CD56 without CD3 (CD3-/CD56+16+). Log transformation of the percentage of NK cells was performed. Parametric statistics were used for analysis. Multiple regression analysis was utilized to examine the contribution of potentially confounding factors on the proportion of NK cells. A p value of < 0.05 was considered statistically significant.


RESULTS
Neonates born to mothers with pre-eclampsia had a significantly higher percentage of NK cells (CD3-/CD56+16+) than those in the control group (pre-eclampsia, mean +/- SD 17 +/- 9% vs. control, mean +/- SD 12 +/- 7.5%; p = 0.001). Multiple regression analysis suggested that umbilical cord blood pH of < 7.2, labor with vaginal delivery and maternal pre-eclampsia were associated with an increased percentage of NK cells in umbilical cord blood.


CONCLUSIONS
Pre-eclampsia is associated with a higher NK cell (CD3-/CD56+16+) subset of lymphocytes in umbilical cord blood than in the control group. This difference cannot be explained by fetal acidosis or the presence of labor.
Bujold
E
E
Department of Obstetrics and Gynecology, Wayne State University/Hutzel Hospital, Detroit, Michigan 48201, USA.
Chaiworapongsa
T
T
Romero
R
R
Gervasi
M T
MT
Espinoza
J
J
Goncalves
L F
LF
Berman
S
S
Yoon
B H
BH
Kim
Y M
YM
D017252:CD3 Complex / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D007694:Killer Cells, Natural / Q000276:immunology*; D016014:Linear Models; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D017452:Receptors, IgG / Q000032:analysis
D017252:CD3 Complex; D019002:CD56 Antigen; D017452:Receptors, IgG