Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid.
OBJECTIVE
We analyzed the vaginal fluid proteome to identify biomarkers of intraamniotic infection among women in preterm labor.


METHODS
Proteome analysis was performed on vaginal fluid specimens from women with preterm labor, using multidimensional liquid chromatography, tandem mass spectrometry, and label-free quantification. Enzyme immunoassays were used to quantify candidate proteins. Classification accuracy for intraamniotic infection (positive amniotic fluid bacterial culture and/or interleukin-6 >2 ng/mL) was evaluated using receiver-operator characteristic curves obtained by logistic regression.


RESULTS
Of 170 subjects, 30 (18%) had intraamniotic infection. Vaginal fluid proteome analysis revealed 338 unique proteins. Label-free quantification identified 15 proteins differentially expressed in intraamniotic infection, including acute-phase reactants, immune modulators, high-abundance amniotic fluid proteins and extracellular matrix-signaling factors; these findings were confirmed by enzyme immunoassay. A multi-analyte algorithm showed accurate classification of intraamniotic infection.


CONCLUSIONS
Vaginal fluid proteome analyses identified proteins capable of discriminating between patients with and without intraamniotic infection.
Hitti
Jane
J
Department of Obstetrics/Gynecology, University of Washington, Seattle, WA, USA.
Lapidus
Jodi A
JA
Lu
Xinfang
X
Reddy
Ashok P
AP
Jacob
Thomas
T
Dasari
Surendra
S
Eschenbach
David A
DA
Gravett
Michael G
MG
Nagalla
Srinivasa R
SR
D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism / Q000382:microbiology*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015331:Cohort Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D007752:Obstetric Labor, Premature / Q000378:metabolism / Q000382:microbiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis* / Q000378:metabolism / Q000382:microbiology; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D014621:Vagina / Q000378:metabolism / Q000382:microbiology*; D055815:Young Adult
D015415:Biomarkers