A bioplex analysis of cytokines and chemokines in first trimester maternal plasma to screen for predictors of miscarriage.
BACKGROUND
We have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 (MIC-1) levels are lower in women in early pregnancy who are destined to miscarriage. While promising, the diagnostic performance of measuring MIC-1 alone was not sufficient for it to be a useful predictive test for miscarriage. Besides MIC-1, there are other cytokines, as well as chemokines, involved in facilitating early pregnancy. We reasoned that screening these factors in maternal plasma could uncover other predictive markers of miscarriage.


METHODS
This was a nested case control study, of 78 women from a prospective study of 462 attending the Early Pregnancy Assessment Unit in the first trimester (EPAU) with a threatened miscarriage; 34 of these subsequently miscarried (cases) and 44 went on to have a normal delivery (controls) Cytokines IL-1β, IL-6 and IL-10, and the chemokines, CXCL8, CCL2, CCL5, CCL7 and CX3CL1 were measured in plasma from our cohort.


RESULTS
The cytokines IL-1β, IL-6, IL-10 and the chemokine CXCL8 were not detectable in first trimester plasma. The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in all samples but levels did not vary across 5-12 weeks of gestation among controls. Plasma levels of these chemokines were no different in the miscarriage cohort compared to controls.


CONCLUSIONS
The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in plasma during the first trimester while IL-1β, IL-6, IL-10 and CXCL8 were not. However, none of the cytokines and chemokines screened were different in maternal plasma in cases or controls. These therefore do not appear to have potential for application as predictive biomarkers of miscarriage.
Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
Natalie J
NJ
Hannan
Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom.
Katerina
K
Bambang
Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
Tu'uhevaha J
TJ
Kaitu'u-Lino
Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom.
Justin C
JC
Konje
Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
Stephen
S
Tong
D000022:Abortion, Spontaneous / Q000097:blood*; D000328:Adult; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D054410:Chemokine CCL7 / Q000097:blood; D054428:Chemokine CX3CL1 / Q000097:blood; D018925:Chemokines / Q000097:blood*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8; D010949:Plasma / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011446:Prospective Studies; D055815:Young Adult
C483024:CCL5 protein, human; C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D054428:Chemokine CX3CL1; D018925:Chemokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D011108:Polymers; D016753:Interleukin-10; C004216:bioplex