title: Amniotic fluid cathelicidin in PPROM pregnancies: from proteomic discovery to assessing its potential in inflammatory complications diagnosis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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<0.0001). A cathelicidin concentration of 4.0 ng/ml was found to be the best cut-off point for identifying PPROM women with both MIAC and HCA. When tested on the validation cohort, a sensitivity of 48%, a specificity of 90%, a likelihood ratio of 5.0, and an area under receiver-operating characteristic curve of 71% were achieved for identification of women with MIAC leading to HCA.
  
  
  CONCLUSIONS
  Our multi-stage study suggests cathelicidin as a candidate marker that should be considered for a panel of amniotic fluid proteins permitting identification of PPROM women with MIAC leading to HCA.
authors: Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
authors: Vojtech
authors: V
authors: Tambor
authors: Marian
authors: M
authors: Kacerovsky
authors: Ctirad
authors: C
authors: Andrys
authors: Ivana
authors: I
authors: Musilova
authors: Helena
authors: H
authors: Hornychova
authors: Lenka
authors: L
authors: Pliskova
authors: Marek
authors: M
authors: Link
authors: Jiri
authors: J
authors: Stulik
authors: Juraj
authors: J
authors: Lenco
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D002821:Chorioamnionitis / Q000175:diagnosis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000175:diagnosis / Q000378:metabolism* / Q000382:microbiology; D005865:Gestational Age; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D016013:Likelihood Functions; D009504:Neutrophils / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011247:Pregnancy; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014357:Trypsin / Q000737:chemistry; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D014357:Trypsin; D054804:Cathelicidins