Proteomic profile of extracellular vesicles in maternal plasma of women with fetal death

Figures & data

Table 1. Demographic and clinical characteristics of the study population.

	Fetal death (n = 47)	Controls (n = 94)	p Vaue
Maternal age (years)^a	28 (20–34)	25 (21–30)	.268
BMI (kg/m^2)^a	32 (25–40)	31 (26–36)	.192
Race (African–American)^b	93.6% (44/47)	93.6% (88/94)	1
Smoking (yes)^b	27.7% (13/47)	16% (15/94)	.119
Alcohol consumption^b	2.1% (1/47)	5.3% (5/94)	.664
Drugs^b	27.7% (13/47)	30.9% (29/94)	.845
Nulliparous^b	40.4% (19/47)	40.4% (38/94)	1
Gestational age at blood collection (weeks)^a	27 (26–36)	27.4 (25–38)	.738
Gestational age at delivery (weeks)^a	28.3 (26–36)	39.6 (39–40)	<.001
Birthweight (g)^a	901 (550–2238)	3302 (3191–3482)	<.001
Fetal sex (male)^b	59.6% (28/47)	59.6% (56/94)	1

BMI: body mass index

^amedian (interquartile range)

^bpercentage (number)

Figure 1. Log₂-fold changes of 19 proteins in fetal death vs controls in the soluble and extracellular vesicle compartments of maternal plasma.

Figure 2. Correlation between the log₂-fold changes of all proteins is significant in either the extracellular vesicles or soluble fractions.

Table 2. Proteins with significantly different plasma concentrations in women with fetal death compared to controls from both EVs and/or soluble fractions.

	Soluble fraction			Extracellular vesicles
	log2 FC	p Value	q Value	log2 FC	p Value	q Value
PIGF	–1.781	<.001	<0.001	–1.271	<.001	<0.001
MIF	0.452	<.001	<0.001	0.621	.001	0.037
Endoglin	0.454	<.001	<0.001	0.346	.012	0.088
RANTES	0.642	<.001	<0.001	0.343	.027	0.167
IL-6	1.009	<.001	0.001	0.859	.002	0.037
MIP1α	0.733	<.001	0.001	0.007	.893	0.934
uPAR	0.428	<.001	0.003	0.195	.115	0.411
TFPI	0.382	<.001	0.003	0.132	.232	0.6
IL-8	0.784	.001	0.005	0.463	.073	0.34
E-Selectin	0.37	.001	0.008	0.142	.37	0.651
VEGFR2	–0.217	.002	0.013	–0.679	.007	0.058
PTX3	0.771	.004	0.023	0.501	.002	0.037
IL-16	0.28	.005	0.029	0.443	.002	0.037
Gal-1	0.3	.006	0.029	0.034	.482	0.722
MCP1	0.425	.006	0.029	0.056	.897	0.934
ADAM12	–0.18	.008	0.035	–0.21	.004	0.041
IGFBP1	0.394	.017	0.073	0.463	.104	0.411
MMP1	0.456	.034	0.116	0.525	.005	0.044
CD163	–0.135	.201	0.486	–0.434	.004	0.041

Log₂FC: log₂ fold-change; PlGF: placental growth factor; MIF: macrophage migration inhibitory factor; RANTES: Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted; IL-6: interleukin-6; MIP1α: macrophage inflammatory protein 1-alpha; uPAR: urokinase plasminogen activator surface receptor; TFPI: tissue factor pathway inhibitor; IL-8: interleukin-8; VEGFR2: vascular endothelial growth factor receptor 2; PTX3: pentraxin 3; IL-16: interleukin-16; Gal-1: galectin-1; MCP1: monocyte chemotactic protein 1; ADAM12: disintegrin and metalloproteinase domain-containing protein 12; IGFBP1: insulin-like growth factor-binding protein 1; MMP1: matrix metalloproteinase-1.

Figure 3. Proteins are differentially expressed between fetal death with and without preeclampsia. The horizontal interrupted line denotes the median concentration in Controls. FD: fetal death. PE: preeclampsia.

Figure 4. Unsupervised clustering of cases with fetal death.

Figure 5. Receiver operating characteristic (ROC) curve for the discrimination of fetal death based on extracellular vesicles (EV) and a combination with soluble fractions.

Figure 6. Gini index score of the top 20 proteins involved in the discrimination of fetal death.