Early pregnancy immune biomarkers in peripheral blood may predict preeclampsia

We performed a prospective cohort study in 197 pregnant women. Peripheral blood was collected between 5 and 16 weeks of gestation. Intracellular cytokine analysis and immunophenotype were performed by flow-cytometry. Serum levels of cytokines and chemokines were analyzed by multiplex assay. 86 patients were eligible for the analysis and 10.5% (n = 9) developed preeclampsia. Patients with preeclampsia had significantly higher percentage of CD3(+)CD4(+)TNF alpha(+) T helper (Th) 1 cells (45.4 +/- 10.3 vs 37.1 +/- 8.5, P = 0.032) and CD3(+)CD4(+)IL17(+) Th 17 cells (2.4 +/- 1.3 vs 1.6 +/- 1.1, P = 0.029) when compared to those of patients without preeclampsia. CD3(+)CD4(+)CD25(+)CD127(dim/-) T regulatory cells (Treg) cells (5.7 +/- 1.2% vs 7.0 +/- 1.6%, P = 0.015) were significantly lower in patients with preeclampsia when compared to those without preeclampsia. Patients with preeclampsia had significantly higher TNF alpha/IL-10 cell ratio (43.8 +/- 10.3 vs 34.3 +/- 7.9, P = 0.005) and Th17/Treg cell ratio (0.5 +/- 0.3 vs 0.2 +/- 0.2, P = 0.011) when compared to those of patients without preeclampsia. IL-8 and Macrophage inflammatory protein (MIP)-1 alpha serum levels were significantly higher in patients with preeclampsia when compared with patients without preeclampsia (Median = 341.0 vs 87.6, U = 152, P = 0.020 and Median = 35.7 vs 17.7, U = 120, P = 0.029 respectively). Serum MCP-1 levels were significantly lower in patients with preeclampsia when compared with patients without preeclampsia (Median = 233.8 vs 390.9, U = 183, P = 0.021). The logistic regression predictive model combining TNF alpha/IL-10 ratios, IL -8 and MCP-1 serum levels had the best performance (AUC = 0.886, 95%CI 0.8-0.9). We concluded that elevated Thl and Th17 cell percentages, elevated TNF alpha/IL-10 and Th17/Treg cell ratios and decreased Treg cell percentages in early pregnancy are associated with preeclampsia.