Isthmin-2 at 12 weeks is the strongest first-trimester preeclampsia marker
A Cambridge team reports in Nature Medicine that low isthmin-2 at 12 weeks of pregnancy was the strongest protein marker of later preeclampsia or fetal growth restriction. Medical Xpress writes more than 200 cases versus more than 200 controls; Nature Medicine counts POPS as 223 cases and 242 controls, the strongest signal among 2,904 proteins. For Sweden, Medical Xpress writes more than 100 cases and 200 controls while Nature Medicine names IMPACT's 432 participants and a separate POPS2 cohort; invasion tests sit beside HEK293 migration.
Science··Evening
Isthmin-2 was the strongest of 2,904 proteins at 12 weeks
Researchers at the University of Cambridge report in Nature Medicine that low circulating levels of the placental protein isthmin-2 at 12 weeks of pregnancy were the strongest indicator of later preeclampsia or fetal growth restriction. Medical Xpress writes the discovery as a comparison of serum from more than 200 women who developed those conditions with more than 200 controls. Nature Medicine counts the same 12-week POPS analysis as 223 cases and 242 controls, and names isthmin-2 as the strongest first-trimester protein signal out of 2,904.[1], [2]
Swedish IMPACT validated in 432 people; the 100-case count stays separate
Medical Xpress describes the Swedish replication as a group of more than 100 cases and 200 controls. Nature Medicine splits the validation across two independent cohorts: Pregnancy Outcome Prediction Study 2 and the Swedish IMPACT study. IMPACT is a multicentre cohort of 432 participants with blood obtained between 11 and 14 weeks; gestational-age-adjusted ISM2 z-scores were lower among cases (p = 2.62 × 10^-12). Nature Medicine does not give the POPS2 sizes, and the Medical Xpress count of more than 100 cases and 200 controls is not merged with IMPACT's 432 participants.[1], [2]
Isthmin-2 loss cut extravillous invasion; HEK293 migration rose
Medical Xpress reports that reduced production of the protein stopped human trophoblast stem cells from turning into the invasive extravillous trophoblast cells that remodel the mother's blood supply, and that cells lacking it failed to make that switch in placental organoids. Nature Medicine reports that knocking down ISM2 in cultured human trophoblast stem cells profoundly inhibited extravillous trophoblast invasion, and that expressing ISM2 in HEK293 cells promoted migration. The team led by Gordon Smith worked from stored serum samples and laboratory models, so the work names a marker and a candidate mechanism without showing that raising isthmin-2 prevents the disease.[1], [2]
