Amniotic fluid cathelicidin in PPROM pregnancies: from proteomic discovery to assessing its potential in inflammatory complications diagnosis

• Published in: PloS one 2012-07, Vol.7 (7), p.e41164-e41164
• Main Authors: Tambor, Vojtech, Kacerovsky, Marian, Andrys, Ctirad, Musilova, Ivana, Hornychova, Helena, Pliskova, Lenka, Link, Marek, Stulik, Jiri, Lenco, Juraj
• Format: Article
• Language: English
• Subjects: Adult; Amniotic fluid; Amniotic Fluid - metabolism; Antibiotics; Antimicrobial Cationic Peptides - biosynthesis; Biology; Biomarkers; Biomedical research; Cell growth; Chorioamnionitis; Chorioamnionitis - diagnosis; Chorioamnionitis - metabolism; Complications; Defense mechanisms; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunosorbent Assay - methods; Fatty acids; Female; Fetal Membranes, Premature Rupture - diagnosis; Fetal Membranes, Premature Rupture - metabolism; Fetal Membranes, Premature Rupture - microbiology; Genotype & phenotype; Gestational Age; Gynecology; Health sciences; Helicobacter pylori; Hospitals; Humans; Hydrogen-Ion Concentration; Infections; Inflammation; Inflammation - metabolism; Leukocytes - metabolism; Likelihood Functions; Likelihood ratio; Medical diagnosis; Medicine; Membranes; Microorganisms; Morbidity; Mycobacterium tuberculosis; Neutrophils - metabolism; Obstetrics; Pathology; Patients; Pediatrics; Peptides; Peptides - chemistry; Physiology; Placenta; Plasma; Pregnancy; Pregnant women; Protein folding; Proteins; Proteomics; Proteomics - methods; ROC Curve; Rodents; Sensitivity and Specificity; Trypsin - chemistry; Tuberculosis; Ulcers; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0041164

Preterm prelabor rupture of membranes (PPROM) complicated by microbial invasion of the amniotic cavity (MIAC) leading to histological chorioamnionitis (HCA) significantly impacts perinatal morbidity. Unfortunately, no well-established tool for identifying PPROM patients threatened by these disorders is available. We performed an unbiased exploratory analysis of amniotic fluid proteome changes due to MIAC and HCA. From among the top five proteins that showed the most profound and significant change, we sought to confirm results concerning cathelicidin (P49913, CAMP_HUMAN), since an ELISA kit was readily available for this protein. In our exploratory proteomic study, cathelicidin showed a ∼6-fold higher concentration in PPROM patients with confirmed MIAC and HCA. We verified significantly higher levels of cathelicidin in exploratory samples (women without both MIAC and HCA: median 1.4 ng/ml; women with both conditions confirmed: median 3.6 ng/ml; p = 0.0003). A prospective replication cohort was used for independent validation and for assessment of cathelicidin potential to stratify women with MIAC leading to HCA from women in whom at least one of these conditions was ruled out. We confirmed the association of higher amniotic fluid cathelicidin levels with MIAC leading to HCA (the presence of both MIAC and HCA: median 3.1 ng/ml; other women: median 1.4 ng/ml; p