Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum

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.

Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study

“…The TNF superfamily of proteins is expressed predominantly by immune cells regulating diverse cell functions, including immune response and inflammation, but also proliferation, differentiation, apoptosis and embryogenesis. A recent Swedish study investigated the inflammatory proteome with the same technology in 22 pregnant women followed longitudinally at two time-points from late pregnancy to week 8 postpartum and found lower levels of TWEAK, TRANCE and TRAIL and higher levels TNFSF14 and OPG during pregnancy in accordance with our findings 20 . In contrast, in their study TNF-beta was higher in pregnancy and TNFRSF9 unchanged but CD40 appeared similar to their results if only comparing our time-points from admission to postpartum.…”

“…A few studies have investigated longitudinal changes in proteins during pregnancy in healthy women [15][16][17][18][19][20] . However, most studies suffer from small sample sizes 15,16,[19][20][21][22][23][24][25] in selected study populations 15,17,24,25 . Some studies have included measurements postpartum 20,21,[23][24][25] in addition to those during pregnancy but no study has included an assessment before conception.…”

Graves' Disease and the Post-partum Period: An Intriguing Relationship

“…Moreover, profound changes in inflammatory and antiinflammatory molecules characterize the pregnancy to PP transition, as recently reported by Brann et al (10) who found a decrease of the major anti-inflammatory markers in the PP period.…”

Human Plasma-Derived 3D Cultures Model Breast Cancer Treatment Responses and Predict Clinically Effective Drug Treatment Concentrations

“…Finally, human plasma was found to be an excellent reservoir for cytokines involved in key cancer hallmarks including: pro-inflammatory cytokines (IL-β1, MIP-1a, TNFα, and RANTES) [68,69], chemokines influencing the invasiveness and migration (SDF-1) [70], cytokines supporting tissue repair/ECM degradation and remodeling (TIMP1, TIMP2, MMP1, and MMP9) [71,72], and cytokines promoting cell growth (INF-γ, PDGF-AB, IL-2, and LIF) [69,73]. In addition, cytokines involved in fibrogenesis (EGF, IGF-I, HGF, and PDGF-AB) [74,75] were found in plasma from healthy subjects and BCa patients. CA125 is a common blood marker tested in breast cancer and ovarian cancer and it allows for the identification and distinction of the plasma from BCa patients [76,77].…”