Abstract
During pregnancy, the woman’s body undergoes tremendous changes in immune system adaptation. The immunological shifts that occur in pregnancy can partially be explained by alterations in hormonal levels. Furthermore, during pregnancy, many autoimmune diseases go into remission, only to flare again in the early postpartum period. Given these important changes in the clinical course of a number of autoimmune disorders, surprisingly little has been done to investigate the inflammatory profile changes across pregnancy and the postpartum period. Thus, the aim of this study was to describe how inflammatory and anti-inflammatory markers change from late pregnancy to the early postpartum period, using a multiplexed assay consisting of both well-known as well as exploratory proteins. Two-hundred-and-ninety women were included in this study and donated a total of 312 blood samples; 198 in late pregnancy (~gw38) and 114 in the postpartum period (~w8). The plasma blood samples were analyzed for 92 immune system related protein markers using Proseek Multiplex Inflammation I panel, a high-sensitivity assay based on proximity extension assay technology. Fifty-six inflammatory and anti-inflammatory markers were significantly different between pregnancy and the postpartum, of which 50 survived corrections for multiple comparisons. Out of these 50 markers, 41 decreased from pregnancy to postpartum, while the remaining 9 increased in the postpartum period. The top five markers with the greatest decrease in the postpartum period were Leukemia inhibitory factor receptor (LIF-R), Latency-associated peptide Transforming growth factor beta-1 (LAP TGF-beta-1), C-C motif chemokine 28 (CCL28), Oncostatin M (OSM) and Fibroblast growth factor 21 (FGF21). Top three markers that increased in the postpartum period were Tumor necrosis factor ligand superfamily member 11 (TRANCE), Tumor necrosis factor ligand superfamily member 12 (TWEAK), and C-C motif chemokine/Eotaxin (CCL11). This study revealed that the majority of the markers decreased from pregnancy to postpartum, and only a few increased. Several of the top proteins that were higher in pregnancy than postpartum have anti-inflammatory and immune modulatory properties promoting pregnancy progress. These results clearly reflect the tremendous change in the immune system in the pregnancy to postpartum transition.
Highlights
IntroductionThe woman’s body undergoes tremendous changes in immune system adaptation
During pregnancy, the woman’s body undergoes tremendous changes in immune system adaptation
Results were presented as Normalized protein expression (NPX), which corresponds to log2(expression), obtained in GenEx software using Olink Wizard by normalizing Cq-values against extension control, interplate control and a correction factor, and NPX corresponds to relative quantification between samples
Summary
The woman’s body undergoes tremendous changes in immune system adaptation. Implantation is characterized by increased levels of pro-inflammatory chemokines, cytokines and growth factors[4]. The M2-milieu continues into the second and third trimester with anti-inflammatory dominance, and the second trimester is characterized by rapid fetal growth and protection against preterm contractions[7]. In addition to the importance of the M1-M2 balance, the T lymphocyte profile plays an important role in the maintenance of pregnancy Both hormonal changes and placental trophoblast immunomodulatory molecules are believed to play a role in the switch to a predominantly T helper type 2 (Th2) cell profile. Pregnancy, with its associated hormones rising, might negatively regulate sub-populations of B cell development to avoid autoimmunity and rejection of the fetus, while enhancing antibody production in other sub-populations of B cells responsible for protection against pathogens[11]. M1 macrophages in the uterus contribute to an inflammatory profile promoting uterine contractions, delivery of the baby, expulsion of the placenta, and uterine involution[16,17]
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