Deep proteome characterization as a tool for identification of novel intraamniotic infection and inflammation biomarkers in preterm birth patients
Background:
Intraamniotic infection and inflammation (IAI) has been demonstrated to be associated with a significantly increased rate of neonatal adverse outcome, even in the absence of demonstrable positive cultures. The biochemical and protein composition of amniotic fluid is altered during pregnancy and reflects both physiological as well as pathological changes in the fetomaternal compartment. Modern proteomic technologies are able to detect and characterize even the slightest changes in protein composition of various biological matrices. Thanks to the ability to both identify and quantify a large number of proteins, this approach seems to be a very promising one for the detection of changes in amniotic fluid protein composition and for the identification of possible biomarkers for the prediction pregnancy related complication.
Objectives:
We employed advanced proteomics in identification of novel potential biomarkers of IAI. The study was performed on amniotic fluid samples from preterm premature rupture of membranes patients with confirmed (n=19) and ruled out (n=19) IAI.
Results:
We successfully identified and quantified 839 amniotic fluid proteins (5% FDR) and selected more than 150 candidates, which showed dysregulated abundance between the two patient groups. To illustrate, these include neutrophil defensin 3, a range of histone proteins (H2, H3, H4 etc), antileukoproteinase and other proteins known to be involved in host against pathogen response, tissue remodeling and cellular death.
Conclusion:
We used multidimensional shotgun proteomics to describe the amniotic fluid proteome and characterize differences among individual patients group, which resulted in a rich group of novel biomarker candidates. These are currently being validated using complementary methods, using both antibody based techniques as well as targeted proteomics approaches.
This work was fully supported by Grant No. NS/10382-3/2009 from the Ministry of Health, Czech Republic.