A role for CXCL13 (BCA-1) in pregnancy and intra-amniotic infection/inflammation.
OBJECTIVE
CXCL13 is a potent chemokine, produced by mature and recently recruited macrophages to sites of inflammation, which has antimicrobial and anti-angiogenic properties. The purpose of this study was to: (1) determine whether CXCL13 is present in maternal serum, umbilical cord blood, and amniotic fluid (AF); (2) to determine if AF concentration changes with intra-amniotic infection/inflammation (IAI); and (3) to localize the production of CXCL13 in chorioamniotic membranes and umbilical cord.


METHODS
A cross-sectional study on maternal serum was performed including patients in the following groups: (1) non-pregnant women (n = 20), (2) normal pregnant women (n = 49), (3) patients at term not in labor (n = 30), and (4) patients in spontaneous labor at term (n = 29). Umbilical cord blood was collected from term neonates with (n = 30) and without labor (n = 28). Amniotic fluid was obtained from patients in the following groups: (1) midtrimester (n = 65); (2) term not in labor (n = 22); (3) term in labor (n = 47); (4) preterm labor (PTL) with intact membranes leading to term delivery (n = 70); and (5) PTL leading to preterm delivery with IAI (n = 79) and without IAI (n = 60). CXCL13 concentrations were determined by enzyme-linked immunosorbent assay. Chorioamniotic membranes and umbilical cords were examined with immunohistochemistry. Non-parametric statistics were used for analysis.


RESULTS
(1) CXCL13 was present in 100% of serum and cord blood samples, and 99% of AF samples (339/343). (2) Serum CXCL13 concentration was significantly higher in pregnant women when compared to non-pregnant women (median 313.3 pg/mL (interquartile range (IQR) 197.2-646.9) vs. 40.5 pg/mL (IQR 29.5-93.5), respectively; p < 0.001). (3) Serum CXCL13 concentration decreased with advancing gestational age (Spearman's Rho = -0.424; p < 0.001). (4) There were no significant differences in the median serum CXCL13 concentration between women at term with and without labor (371.6 pg/mL (IQR 194.3-614.3) vs. 235.1 pg/mL (IQR 182.8-354.7), respectively; p = 0.6). (5) The concentration of CXCL13 in AF did not change with gestational age (p = 0.1). (6) Patients with PTL and delivery with IAI had a significantly higher median concentration of CXCL13 than those without IAI (median 513.2 pg/mL (IQR 199.7-2505.5) vs. 137.3 pg/mL (IQR 96.7-209.6), respectively; p < 0.001) and those who delivered at term (133.7 pg/mL (IQR 97.8-174.8); p < 0.001). (7) Spontaneous labor did not result in a change in the median AF concentration of CXCL13 (labor: 86.9 pg/mL (IQR 55.6-152.0) vs. no labor: 77.8 pg/mL (IQR 68.0-98.0); p = 0.8). (8) CXCL13 was immunolocalized to macrophages in fetal membranes and umbilical vein.


CONCLUSIONS
(1) We report for the first time the presence of CXCL13 in AF. (2) AF CXCL13 concentrations are dramatically increased in IAI. (3) Unlike other chemokines, AF and serum CXCL13 concentrations did not change with spontaneous parturition.
Nhan-Chang
Chia-Ling
CL
Perinatology Research Branch, Intramural Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD/NIH/DHHS, Hutzel Women's Hospital, Detroit, MI 48201, USA. prbchiefstaff@med.wayne.edu
Romero
Roberto
R
Kusanovic
Juan Pedro
JP
Gotsch
Francesca
F
Edwin
Samuel S
SS
Erez
Offer
O
Mittal
Pooja
P
Kim
Chong Jai
CJ
Kim
Mi Jeong
MJ
Espinoza
Jimmy
J
Friel
Lara A
LA
Vaisbuch
Edi
E
Than
Nandor Gabor
NG
Mazaki-Tovi
Shali
S
Hassan
Sonia S
SS
D000649:Amniocentesis; D000653:Amniotic Fluid / Q000378:metabolism*; D054382:Chemokine CXCL13 / Q000097:blood*; D003430:Cross-Sectional Studies; D005321:Extraembryonic Membranes / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007752:Obstetric Labor, Premature / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood*; D047929:Term Birth / Q000378:metabolism*; D014470:Umbilical Cord / Q000378:metabolism
C110663:CXCL13 protein, human; D054382:Chemokine CXCL13