A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

Hannan, Natalie J.; Bambang, Katerina; Kaitu’u-Lino, Tu’uhevaha J; Konje, Justin C.; Tong, Stephen

doi:10.1371/journal.pone.0093320

Cited by 21 publications

(22 citation statements)

References 40 publications

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“…In conclusion, we have shown for the first time that the relative expression of PER between 4 weeks of gestation and control ultrasound in the 6th week of gestation is significantly altered in asymptomatic women with subsequent miscarriage compared to women with ongoing pregnancy, therefore suggesting systemic PER levels as a potential promising biomarker for pregnancy outcome assessment. The development of an early-screening test to identify patients who are at risk of miscarriage in the actual pregnancy would be useful for several reasons: a miscarriage means an enormous distress for the patient and a predictive test with a negative result could be used to reassure anxious patients [ 31 , 32 , 36 , 37 , 39 , 40 ]. On the other hand, a predictive test with a positive result can warn the patients in a very early stage of pregnancy [ 39 ], and will prohibit unnecessary prolongation of the current pregnancy by supplementation of high doses of progesterone, as often done in women after ART.…”

Section: Discussionmentioning

confidence: 99%

Serum periostin levels in early in pregnancy are significantly altered in women with miscarriage

Freis

Schlegel

Kuon

et al. 2017

Reprod Biol Endocrinol

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BackgroundMiscarriage is a common complication in pregnancy and there is still a lack of biomarkers usable in asymptomatic patients before the event occurs. Periostin (PER), whose levels rise particularly during injury or inflammation, has been shown to play an important local role in implantation and early embryonic development. As PER has been described as a biomarker in various medical conditions we intended to evaluate if changes in PER serum levels may help to identify women at risk for spontaneous abortion in the first trimester.MethodsWomen between 18 and 42 years without confounding comorbidities who conceived by IVF/ICSI and ovarian hyperstimulation were analysed in the study after informed consent. Maternal serum samples from 41 patients were assessed at the time of pregnancy testing (PT) and the following first ultrasound checkup (US). Patients were subsequently divided in two groups: (1) patients with subsequent miscarriage in the first trimester (n = 18) and (2) patients with ongoing pregnancy (n = 23), allowing for statistical analysis and investigating the change of PER levels per individual. PER levels were measured using enzyme-linked immunosorbent assay. Statistical analysis was performed using the Fisher exact and Student’s t test. p ≤ 0.05 was considered to be significant.ResultsThere was no significant difference concerning possible confounders between the two groups. We did not find any significant difference in PER levels at the time point of PT or US. By investigating the interindividual changes of PER between the two time points however, we observed that patients with a following miscarriage showed increasing levels of PER at the time point of PT compared to US in contrast to patients with an ongoing pregnancy who demonstrated a decrease in PER levels. These alterations were significant in the absolute as well as in the relative comparison.ConclusionThe relative expression of PER between PT and US is significantly altered in asymptomatic women with subsequent miscarriage compared to women with ongoing pregnancy. Therefore systemic PER levels might represent a potential promising biomarker for the assessment of pregnancy outcome.Trial registrationNot applicable.

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Section: Discussionmentioning

confidence: 99%

Serum periostin levels in early in pregnancy are significantly altered in women with miscarriage

Freis

Schlegel

Kuon

et al. 2017

Reprod Biol Endocrinol

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“…Raw fluorescence data were analyzed with software using the 5-parameter logistic method. Detailed procedures of the Bio-Plex ® Suspension Array System have been described elsewhere (15)(16)(17).…”

Section: Methodsmentioning

confidence: 99%

CSF1 is involved in breast cancer progression through inducing monocyte differentiation and homing

Ding

Guo

et al. 2016

International Journal of Oncology

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Despite the great progress in breast cancer research and treatment, measures for efficient targeting of triple‑negative breast cancer (TNBC) are still lacking. The well‑established dependency of cancer cells on their microenvironment suggests that targeting the tumor niche might form a novel therapeutic approach. We identified the tumor‑associated macrophage (TAM) infiltration in breast cancer tissues by immunohistochemistry, and analyzed overall survival (OS). U937 co‑cultures with MDA‑MB‑231, MDA‑MB‑468 and MCF‑7, respectively, to simulate in vivo cellular interactions were assessed. In hormone‑independent breast cancer cell conditioned media (CM), U937 differentiates into M2 macrophage as identified by morphological changes and expression of specific surface antigens CD163 and CD204. Moreover, MDA‑MB‑231 recruits U937, and colony‑stimulating factor 1 (CSF1) level in MDA‑MB‑231 and MDA‑MB‑468 CM is much higher than that of MCF‑7. Overexpression of CSF1 in MCF‑7 fails to rebuild its aggressiveness both in vitro and in vivo since CSF1 was not found extracellularly, while genetic inhibition of CSF1 in MDA‑MB‑231 abrogates TAM infiltration and consequently reduces tumorigenesis in non‑obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Using various strategies we demonstrate that CSF1‑induced TAMs specifically support breast cancer progression. Importantly, our results may reveal the efficacy of using targeted therapy against tumor niche and indicate that CSF1 inhibition may limit some breast cancer progression.

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“…CCL2 or MIP-1 is considered to cause a shift towards the Th2-response of decidual leukocytes [ 25 ] . However, in contrary to this observation, serum levels of CCL-2/macrophage inflammatory protein (MIP-1) were elevated in women with recurrent spontaneous abortion (RSA) after spontaneous abortion occurred [ 26 ] , whereas other studies did not see any significant alteration [ 5 ] .…”

Section: Introductionmentioning

confidence: 95%

“…Spontaneous abortion is one of the most common complications in early pregnancy and affects 10–20% of all pregnancies [ 1 – 5 ]. Symptoms include vaginal bleeding, and/or uterine cramping, but only 28% of symptomatic patients are experiencing spontaneous abortions later in pregnancy [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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

Freis

Schlegel

Daniel

et al. 2018

Reprod Biol Endocrinol

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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.

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A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

Cited by 21 publications

References 40 publications

Serum periostin levels in early in pregnancy are significantly altered in women with miscarriage

Serum periostin levels in early in pregnancy are significantly altered in women with miscarriage

CSF1 is involved in breast cancer progression through inducing monocyte differentiation and homing

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

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