Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid

• Published in: American journal of obstetrics and gynecology 2010-07, Vol.203 (1), p.32.e1-32.e8
• Main Authors: Hitti, Jane, MD, Lapidus, Jodi A., PhD, Lu, Xinfang, MS, Reddy, Ashok P., PhD, Jacob, Thomas, PhD, Dasari, Surendra, PhD, Eschenbach, David A., MD, Gravett, Michael G., MD, Nagalla, Srinivasa R., MD
• Format: Article
• Language: English
• Subjects: Adult; Amniotic Fluid - metabolism; Amniotic Fluid - microbiology; Biological and medical sciences; Biomarkers - analysis; Biomarkers - metabolism; Cohort Studies; Electrophoresis, Gel, Two-Dimensional; Female; Gynecology. Andrology. Obstetrics; Humans; intraamniotic infection; Mass Spectrometry; Medical sciences; Obstetric Labor, Premature - metabolism; Obstetric Labor, Premature - microbiology; Obstetrics and Gynecology; Pregnancy; Pregnancy Complications, Infectious - diagnosis; Pregnancy Complications, Infectious - metabolism; Pregnancy Complications, Infectious - microbiology; preterm labor; Prospective Studies; proteomics; Proteomics - methods; ROC Curve; Vagina - metabolism; Vagina - microbiology; vaginal fluid; Young Adult
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2010.03.037

Objective We analyzed the vaginal fluid proteome to identify biomarkers of intraamniotic infection among women in preterm labor. Study Design 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. Conclusion Vaginal fluid proteome analyses identified proteins capable of discriminating between patients with and without intraamniotic infection.