Cytokines in relation to hCG are significantly altered in asymptomatic women with miscarriage – a pilot study

Abstract

BackgroundSpontaneous abortion is one of the most common complications in early pregnancy. A preventive test to identify women who will experience a miscarriage, even before first symptoms occur, is not established. Activation of maternal immunological tolerance seems to be essential for early fetal development and various cytokines have been described in different stages of pregnancy. Therefore, we aimed to investigate if chemokine levels at the time of pregnancy testing relative to human Choriogonadotropin (hCG) are altered in patients who will experience a miscarriage in this pregnancy.MethodsWe obtained blood samples from 39 women. Dependent on the follow-up, patients with a positive pregnancy test were subsequently divided in two groups: ongoing pregnancy (n = 22) and miscarriage (n = 17) in this pregnancy. Immunological and endocrine profiling of maternal plasma at the time of pregnancy testing (5th week of gestation) was performed for each group at the time of pregnancy test using Multiplex and ELISA analysis.ResultshCG was significantly decreased in patients with abortion whereas levels of IL-1ra, MIP-1a and TNF-alpha were significantly increased. GCSF/ IL-1ra-ratio was 1.66-fold increased in patients with ongoing pregnancy. TGF-beta /MIP1a-ratio was significantly 3.45-times higher in patients with miscarriage. Comparing patients with ongoing pregnancy to patients experiencing a miscarriage, we could demonstrate significant alterations of the ratios MIP1a/hCG, IL-1ra/hCG, TNFalpha/hCG, MCP1/hCG, IL-6/hCG, TPO/hCG and TGF-beta1/hCG. The strongest effects were seen for the ratio MIP1a/hCG, IL-1ra/hCG and TNFalpha/hCG.ConclusionsWe have shown that cytokines in relation to hCG after 4 weeks of gestation are significantly altered in women with miscarriage, promising potential as a prognostic biomarker.

Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

“…RSA refers to two or more consecutive spontaneous abortions before 20 weeks of pregnancy, and its incidence is approximately 5% (92)(93)(94). Studies have confirmed that compared with healthy controls, the expression of TGF-b1 in the decidual tissue of RSA patients is significantly decreased (95,96).…”

IL‐10 to TNFα ratios throughout early first trimester can discriminate healthy pregnancies from pregnancy losses

“…Conversely, one study found that the IL-10 concentration is significantly lower in pregnancies that go on to have live births 20 . In patients who had undergone IVF, TNFα levels in the 5th week of gestation were significantly higher in women who went on to have a pregnancy loss 21 and also in women who had already miscarried, TNFα levels…”

“…This article is protected by copyright. All rights reserved been identified as potential markers of immune dysregulation in studies on pregnant women [15][16][17][18][19][20][21][22][23] .…”

Effect of Intralipid infusion on peripheral blood T cells and plasma cytokines in women undergoing assisted reproduction treatment

“…However, a sustained increase in plasma CCL2 is associated with recurrent spontaneous abortion (RSA) 72 . At very high levels, elevated plasma CCL3 is also linked with RSA 73 . IL‐21 is associated with Th1‐ and Th17‐polarised immune responses, and the 15% increase in median IL‐21 in post‐Intralipid blood samples might reflect elevated production by Th17 cells and NK cells 74 …”