Altered autophagy induction by sera from pregnant women with pre‐eclampsia: a case–control study

Objective Mechanisms leading to pre‐eclampsia remain incompletely defined. Autophagy is a conserved process necessary for cell survival under adverse conditions. We hypothesised that sera from women with healthy pregnancies and women with pre‐eclampsia differed in autophagy induction. Design A case–control study. Setting Weill C ornell M edical C ollege. Population Twenty‐four normotensive pregnant women and 20 women with pre‐eclampsia. Methods Sera were incubated with peripheral blood mononuclear cells ( PBMC s) from female donors. After 48 hours the PBMC s were lysed and the intracellular concentration of p62 was determined by enzyme‐linked immunosorbent assay ( ELISA ). Its concentration is inversely proportional to the extent of autophagy induction. Serum endoglin, interleukin 13 ( IL –13), insulin‐like growth factor 1 ( IGF –1), and transforming growth factor β 1 ( TGF – β 1) levels were quantitated by ELISA . Main outcome measures Differences in autophagy induction and serum mediator levels in the two groups. Results Autophagy induction increased with gestational age in sera from normotensive women ( P  = 0.0045), but not in women with pre‐eclampsia. In the presence of an autophagy inducer, the capacity for autophagy induction decreased with gestational age in sera from women with pre‐eclampsia ( P  = 0.0235), but not from controls. Endoglin concentrations were positively associated with the extent of autophagy induction in controls only ( P  = 0.0141). There was no association between autophagy and serum IL –13, IGF –1, or TGF – β 1 levels. Conclusions Sera from women with pre‐eclampsia differ from normotensive women by their inability to induce autophagy as a function of gestational age.