Immune System Can Detect Disease During Pregnancy

Pregnancy is a challenge for the mother's immune system from the outset. Half of the genes in the fetus are foreign to her body. The immune system has to strike a balance between tolerating the fetus and protecting the mother and fetus from infections. Throughout the pregnancy, an immunological balance takes place between mother and child.

Maternal serum cytokine profiling can be used to gain detailed information about maternal inflammatory status, fetal stress, and early signs of immunological disturbance. Immunological profiling by simultaneous measurement and analysis of multiple cytokines provides higher sensitivity and depicts ongoing inflammatory processes better than single cytokine measurements as cytokines comprise complex functional networks.

Clinical Scientists at the Norwegian University of Science and Technology (Trondheim, Norway) and their associates selected women with normal singleton pregnancies and were chosen from five different cohorts. Serum samples were collected between 2002 and 2015 at two hospitals in Trondheim, and between 2003 and 2012 at Haukeland University Hospital (Bergen, Norway).

The team performed cytokine profiling of 1,149 longitudinal serum samples from 707 pregnant women to map immunological changes from first trimester to term and beyond. The serum samples were analyzed for 27 cytokines (Bio-Plex Pro Human Cytokine 27-plex Assay) in single replicates using Luminex xMAP Technology on a Bio-Plex 200 System (Bio-Rad Laboratories, Hercules, CA, USA). High-sensitivity CRP (hsCRP) measurements in serum was obtained using Human CRP Quantikine kit (R&D Systems, Minneapolis, MN, USA). Some samples were analyzed for hsCRP using turbidimetric assay and measured at 571 nm by a Siemens Advia Chemistry XPT system (Siemens Healthineers, Erlangen, Germany).

The investigators reported that the serum levels of 22 cytokines and CRP followed diverse but characteristic trajectories throughout pregnancy, consistent with staged immunological adaptations. Eotaxin showed a particularly robust decrease throughout pregnancy. A strong surge in cytokine levels developed when pregnancies progressed beyond term and the increase was amplified as labor approached. Maternal obesity, smoking and pregnancies with large fetuses showed sustained increase in distinct cytokines throughout pregnancy. Multiparous women had increased cytokine levels in the first trimester compared to nulliparous women with higher cytokine levels in the third trimester. Fetal sex affected first trimester cytokine levels with increased levels in pregnancies with a female fetus.

Ann-Charlotte Iversen, PhD, a Professor of Molecular Biology and senior author of study, said, “A cytokine profile is a very sensitive measurement of the immune system, and now we have a better understanding of the immune system’s normal development in pregnancy and how it’s affected. Once we’ve mapped the changes that characterize various pregnancy complications, it will show us which abnormalities we should look for in order to detect disease development as early as possible. Having this sensitive a method will enable us to point out high-risk pregnancies so we can follow up the mother and fetus more closely. That’s our goal.”

The authors concluded that their findings unravel important immunological dynamics of pregnancy, demonstrate how both maternal and fetal factors influence maternal systemic cytokines, and serve as a comprehensive reference for cytokine profiles in normal pregnancies. The study was originally published on October 14, 2021 in the journal Frontiers in Immunology.

Related Links:
Norwegian University of Science and Technology
Haukeland University Hospital
Bio-Rad Laboratories
R&D Systems
Siemens Healthineers