Charlene Cook,a 38-year-old primigravida,is 35 weeks pregnant.Until recently she has had an uneventful pregnancy.Two weeks ago,her obstetrician noted lower-extremity edema,trace protein in her urine (10-20 mg/dl),and normal blood pressure (120/80 mmHg).At today's appointment her blood pressure is elevated at 160/100 mmHg,she has marked proteinuria (3+; 300 mg/dl),worsening of ankle swelling,facial and hand swelling,and she mentions sudden onset of headache and visual disturbance.Charlene is admitted immediately to hospital and is diagnosed with pre-eclampsia.Within hours she is induced and gives birth to a healthy baby girl.In the context of uterine NK-cell function,which of the following is inconsistent with the cause of Charlene's pre-eclampsia?

Question

Quizplus · Accepted Answer

The correct answer is d. The conditions for adequate nourishment of the fetus are established early in pregnancy and involve converting the narrow spiral arteries of the uterus into wider conduits after extravillous trophoblast invasion. These high-conductance vessels direct sufficient blood flow to placenta during pregnancy and serve to regulate the blood pressure of the mother. Uterine NK cells interact with invading extravillous trophoblast cells using both inhibitory and activating receptors; which receptors are used is dependent on maternal haplotype. The KIR A haplotype lacks the activating KIR2DS1 receptor, which engages the C2 epitope, but the KIR B haplotype expresses this receptor. Additionally, the KIR A haplotype expresses the strong inhibitory KIR2DL1 receptor which also engages the C2 epitope. In mothers who are homozygous for KIR A, the uterine NK cells encounter C2 epitopes on extravillous trophoblast cells using these strong inhibitory receptors. This causes an imbalance between inhibitory and activating signals delivered to the NK cells; KIR2DL1 will deliver strong inhibitory signals through the C2 epitope, but in the absence of KIR2DS1 there will be no activating signals delivered through the C2 epitope. If the uterine NK cells are not activated sufficiently, they will not secrete the cytokines and growth factors needed for complete invasion of the extravillous trophoblast cells, remodeling of the maternal spiral arteries, and promotion of new blood vessels. If the baby is homozygous for the C1 epitope (which would happen 100% of the time if both mother and father were homozygous for the C1 epitope), then failure to activate through KIR2DS1 or induce inhibition through KIR2DL1 is no longer an issue. In the context of uterine NK cells, the increased risk for pre-eclampsia arises only when there is a combination of maternal homozygosity of the KIR A haplotype, and the fetus inherits the C2 epitope from the father.

Charlene Cook,a 38-Year-Old Primigravida,is 35 Weeks Pregnant