Unveiling the pathophysiology of gestational diabetes: Studies on local and peripheral immune cells.

Gestational diabetes mellitus (GDM) has been associated with impaired maternal immune response. Our aim was to review the available literature linking immune cells profile to GDM, in order to comprehend the role that different subpopulations play in the development of this pathology. We searched in PubMed for studies published in the last decade on circulating levels and placenta expression of immune cells on GDM. We identified 18 studies with several differences regarding the study design, clinical characteristics, number of participants, cell subpopulation and type of sample. Most studies assessed only one subpopulation either in peripheral blood or placenta and did not analyse functional properties of the cells. The most frequently evaluated immune cells were T lymphocytes, especially regulatory T (Tregs), and natural killer (NK) cells in the peripheral blood, and placental macrophages. No studies analysing B cells were identified, and only one study each evaluating γδT cells, dendritic cell (DC) and monocytes was found. Although there are controversies, at least one study reported positive association between GDM and CD4+ (activated), Tregs, Th17 and γδT cells; neutrophil/lymphocyte; NK cell (cytotoxic); macrophages; and monocytes. The number of studies is still small, so caution should be exercised in interpreting the data, and further research is required to validate these findings and establish the role of adaptive and innate immune cells in GDM pathophysiology.

Angiogenic factors and uterine Doppler velocimetry in early- and late-onset preeclampsia.

OBJECTIVE: To assess correlations between maternal serum levels of pro- and anti-angiogenic factors with uterine perfusion in women with early- compared with late-onset preeclampsia, and in healthy pregnant women. DESIGN: Case-control study. SETTING: Antenatal care clinic located within a hospital (São Bernardo do Campo, Brazil). POPULATION: We enrolled 54 preeclamptic and 54 healthy control women who were coming for routine ultrasound at 28-36 weeks' gestation. METHODS: All participants had uterine artery and umbilical Doppler studies and a blood sample to assess maternal serum levels of soluble fms-like tyrosine kinase-1, soluble endoglin, adiponectin and plasminogen activator inhibitor-1. All angiogenic factors were measured using enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Levels of pro- and anti-angiogenic factors in maternal serum, and uterine artery Doppler findings. RESULTS: Concentrations of soluble fms-like tyrosine kinase-1 and soluble endoglin were significantly higher in preeclamptic than control women (p < 0.0001 and p < 0.0001, respectively), especially in those with early-onset (<34 weeks) preeclampsia. These two anti-angiogenic mediators were significantly correlated with increased uterine artery Doppler in the preeclamptic women. Plasminogen activator inhibitor-1 levels were significantly higher in preeclampsia (p = 0.03) but unrelated to uterine artery resistance. Adiponectin levels were similar in cases and controls, independent of body mass index and unrelated to uterine artery resistance. CONCLUSION: Preeclamptic patients have increased soluble fms-like tyrosine kinase-1 and soluble endoglin serum levels and this increase is directly correlated with uterine artery resistance, especially in those with early-onset preeclampsia.