Sera from early-onset, severely preeclamptic women directly modulate HLA-E expression in the EA.hy296 endothelial cell line.

The expression of endothelial HLA-E in the context of the systemic inflammatory response observed in preeclampsia has not been established. An experimental study was designed to determine the effect of the sera of pregnant women on the expression of HLA-E in EA.hy296 endothelial cells. First, measurements of protein fractions were performed in sera from early-onset, severely preeclamptic women without HELLP syndrome, in which there was no significant difference in total proteins between the groups, but a reduced level of plasma albumin and an increase in α1-globulin were observed in both groups of pregnant women compared with non-pregnant women. Measurements of colloid osmotic pressure (COP) using a recalculated albumin/globulin ratio formula determined only a significant decrease in COP in all pregnant groups compared with non-pregnant women. The expression of membrane HLA-E was increased in EA.hy296 endothelial cells stimulated with sera of early-onset, severely preeclamptic women, while recombinant interferon-γ (IFN-γ) significantly reduced the expression of membrane HLA-E. Pro-inflammatory cytokines were measured by Luminex in the serum samples, and increased levels of tumor necrosis factor (TNF) and decreased levels of IFN-γ were observed in early-onset, severe preeclampsia compared with normal pregnancy. Moreover, soluble HLA-E was detected in these serum samples by Western blot and ELISA, but no significant difference was found. This raises the possibility that a systemic inflammatory response promotes a compensatory mechanism of COP balance in severe preeclampsia by release of inflammation-induced factors, including endothelial HLA-E. Evidence is now provided regarding HLA-E expression by EA.hy296 cells.

The production of MLR-blocking factors after lymphocyte immunotherapy for RSA does not predict the outcome of pregnancy.

PROBLEM: The questions of whether production of mixed lymphocyte reaction-blocking factors (MLR-BFs) after immunotherapy with lymphocytes for recurrent spontaneous abortion (RSA) has prognostic value and whether cytotoxic antibodies are also involved were tested. METHOD OF STUDY: A prospective study with 33 patients who had a history of two or more abortions, lacking MLR-BFs, was carried out. The patients received immunizations with lymphocytes and 6 weeks or later were tested for seroconversion of MLR-BFs. Seventeen of these thirty-three patients were evaluated for antipaternal cytotoxic antibodies. The results were correlated with the outcome of the next pregnancy after treatment. RESULTS: Eighty percent of the 33 patients had a live child. Of those patients having success, only 50% produced MLR-BFs. Of those patients having a new loss, five did and two did not produce MLR-BF (P > 0.05). Regarding the 17 patients tested for cytotoxic antibodies, 4 of the 5 patients who tested positive had a new abortion, whereas only 1 of 12 whose tests remained negative did not have gestational success (P < 0.01). CONCLUSION: The presence of MLR-BFs is not a prognostic criterium for the outcome of pregnancy after alloimmunotherapy, and, consequently, it is not a good diagnostic tool for RSA of alloimmune cause.