P 56 The role of anti- and pro-inflammatory cytokines on the expression of the tolerogenic HLA class Ib molecules in relation to pregnancy and preeclampsia

Abstract

Introduction Preeclampsia (PE) is a multi-systemic pregnancy disorder and an important cause of fetal and maternal morbidity and mortality worldwide. Although the exact etiology behind PE is unclear, one widely accepted hypothesis propose that a maladapted immune response in the mother cause inadequate trophoblast invasion and remodeling of the spiral arteries, leading to hypoxia and ischemia. Whereas uncomplicated pregnancies is characterized by immunological tolerance towards the fetal cells established through immunological mediators such as HLA-C and the non-classical HLA-Ib molecules and regulatory immune cells, PE is characterized by the presence of pro-inflammatory leukocytes and cytokines. The direct consequence of the presence of the pro-inflammatory cytokines in the local environment and on the fetal cells is less studied. Objectives The aim is to characterize the effect of the anti- and pro-inflammatory cytokines on the expression of HLA class I molecules on the trophoblast cell line JEG-3 and primary placenta tissue. Materials and methods JEG-3 cells are incubated in the presence of various concentrations of anti- and pro-inflammatory cytokines for up to 72 h. HLA-C, -E and -G surface expression is characterized by flow cytometry, mRNA levels of HLA class Ia and Ib is quantified by droplet digital PCR, and expression of the different isoforms of HLA-G (HLA-G1-7) is analyzed by fragment analysis. Results Our preliminary data suggests an upregulation of the HLA-Ib molecules upon culture with IFN-γ, whereas IL-12 seems to slightly downregulate the expression of HLA-G. The effect on mRNA level and on expression of different isoforms of HLA-G is currently being investigated. Conclusion Expression of HLA-I molecules seems to be affected by the presence of specific cytokines in the local environment. Whether this act of balancing is also seen in primary placenta tissue from healthy pregnancies or cases of PE will be determined in nearest future.