99 Endogenous activation of inflammatory profiles Th1 and Th17 in lymphocytes from pregnant women with preeclampsia

Abstract

Introduction Preeclampsia (PE) is a systemic disease characterized by multiple alterations in the maternal organism and clinically identified by hypertension and proteinuria that manifest in the second half of gestation. Studies indicate that PE has an exacerbated inflammatory response and a state of maladaptation of immunological tolerance, characterized by abnormal activation of the innate and adaptive immune system. Objectives This study characterized the Th cell subsets (Th1, Th2, Th17 and Treg) in pregnant women with PE and normotensive (NT) pregnant women. Methods Thirty-eigth pregnant women were studied, 20 women with PE and 18 NT, matched by gestational age. Mononuclear cells from peripheral blood obtained from preeclamptic and NT women were analyzed for the endogenous expression of transcription factors involved in the characterization of Th cell subsets. The expression of intracytoplasmic transcription factors T-bet (Th1), GATA-3 (Th2), ROR γ T (Th17) and FoxP3 (Treg) were evaluated by flow cytometry, using specific monoclonal antibodies labeled with fluorochromes. The gene expression of these transcription factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR). Differences between groups were analyzed by non-parametric tests with significance level set at 5%. Results Flow cytometry analysis demonstrated an inflammatory profile in PE group. Th1 and Th17 subsets showed higher media fluorescence intensity (MFI) and percentage of cells expressing the transcription factor T-bet and ROR γ T respectively, compared with NT women. The anti-inflammatory Th2 profile was decreased in percentage of cells expressing GATA-3, but MFI in PE was elevated when compared to NT. No significant difference of MFI was observed in Treg profile between groups, but the percentage of lymphocytes expressing FoxP3 was increased in NT than in PE group. The gene expression of the transcription factors demonstrated greater values of T-bet and ROR γ T in women with PE when compared to the NT. Significantly lower expression of GATA-3 and FoxP3 genes were detected in preeclamptic women than in NT group. Conclusion The increase of inflammatory profiles Th1 and Th17 and the decrease of anti-inflammatory subsets Th2 and Treg both in gene expression and intracytoplasmic transcription factors in women with PE suggest that there is an imbalance in maternal tolerance in PE and confirms the activation of inflammatory profile in subpopulations of Th cells in the pathogenesis of the disease. Financial support – FAPESP 2014/25124-7 and 2012/24697-8.