Pregnancy-associated relationships between serum content of Cu2+, Mg2+, Zn2+, Se2+ and peripheral blood lymphocyte sub-populations in Kuwaiti women

We have recently demonstrated pregnancy-associated changes in subpopulations of peripheral blood lymphocytes by healthy Kuwaiti women to be consistent with elevated immune activation balanced by immunosuppressive processes. We have further shown that when compared with nonpregnant subjects, pregnant women exhibited lower serum concentrations of the divalent cations zinc and selenium, and elevated levels of copper and magnesium. In this study we assess the relationship between serum levels of divalent cations and activated lymphocyte subpopulations in a group of 32 normal healthy premigravid women during the third trimester of pregnancy (mean age 28.9 years +/- SE, 0.81), and compared with a matched population of non-pregnant women (mean age 23.6 years +/- SE, 1.8). Peripheral venous blood was collected, followed by Q-Prep lysis, labeling with flourescein-isothiocyanate (FITC) or phycoerythrin (RD1) conjugated monoclonal antibodies (mAb) for lymphocyte surface antigens of interest; and 2 color fluorescence analysis using an automated flow cytometer (Epics XL, Coulter) and reported as a fraction of the T cell population. The serum fraction of each sample was analyzed for content of selected metals using graphite furnace atomic absorption which was reported as mug/l of whole blood. When compared to non-pregnant subjects, pregnant women exhibited significantly elevated levels of CD3+CD16+CD56+ (p = 0.036), CD4+CD25+ (p = 0.050), CD4+CD45RA+ (p = 0.046), CD4+CD54+ (p = 0.029), CD8+CD25+ (p = 0.040), and CD8+HLADR+ (p = 0.002). Serum from pregnant subjects contained elevated copper (p = 0.00), and magnesium (p = 0.0130), but lower zinc (p = 0.005), and selenium (p = 0.017) than the non-pregnant cohort, consistent with results of our previous studies. Pearson's correlation coefficients were calculated to study correlation between serum trace elements and frequency of major lymphocyte subpopulations. It was observed that within the pregnant group a direct correlation existed between serum copper and percentage of CD3+CD16+CD56+ (p = 0.013), while inverse relationships were noted between this subset and magnesium (p = 0.020), and between CD4+CD54+ and zinc (p = 0.020). Divalent cations are cofactors for enzymes such as the vasodilator prostacyclin, and the vasoconstrictor thromboxane, which act as key hemodynamic regulatory elements in pregnancy. Imbalances of trace elements affect activities of these enzymes sometimes causing pathological vasoconstriction in pregnancy. Relationships between their serum levels and lymphocyte subsets suggests a possible undescribed immunoregulatory role for these metals and the enzymes they control.