title: Soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) in amniotic fluid: modulation by infection and inflammation.
abstract: OBJECTIVE
  The receptor for advanced glycation end products (RAGE) has been proposed to participate in the innate and adaptive immune responses. RAGE can induce production of pro-inflammatory cytokines and chemokines, as well as neutrophil chemotaxis in a manner that may be suppressed or stimulated by soluble, truncated forms of RAGE including the soluble form of RAGE (sRAGE) and endogenous secretory RAGE (esRAGE). The objective of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in the amniotic fluid concentration of sRAGE and esRAGE.
  
  
  METHODS
  Amniotic fluid (AF) was retrieved from patients in the following groups: 1) mid-trimester (14-18 weeks of gestation; n=68); 2) term not in labor (n=24); 3) term in labor (n=51); 4) preterm labor and intact membranes (n=124); and 5) preterm PROM (n=80). Intra-amniotic infection and inflammation were defined as the presence of a positive amniotic fluid culture for microorganisms and an AF interleukin-6 concentration >or=2.6 ng/mL, respectively. The AF concentration of sRAGE and esRAGE were determined using specific and sensitive ELISAs which measured total immunoreactive sRAGE and esRAGE, respectively. Patients were matched for gestational age at amniocentesis to compare the AF concentration of sRAGE and esRAGE in patients with and without IAI. Non-parametric statistics were used for analysis and a P<0.05 was considered significant.
  
  
  RESULTS
  1) Patients at term not in labor had higher median AF concentrations of sRAGE and esRAGE than those in the mid-trimester (P<0.001 for both comparisons) and those at term in labor (P=0.03 and P=0.04, respectively); 2) patients with preterm labor and intact membranes with intra-amniotic infection/inflammation (IAI) had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.02 and P=0.005, respectively); 3) similarly, patients with preterm PROM with IAI had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.03 and P=0.02, respectively).
  
  
  CONCLUSIONS
  Intra-amniotic infection/inflammation is associated with increased amniotic fluid concentrations of sRAGE and esRAGE. Changes in the amniotic fluid concentration of sRAGE and esRAGE may represent part of the immune response to intra-amniotic infection/inflammation.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland, USA. prbchiefstaff@med.wayne.edu
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Jimmy
authors.initials: J
authors.lastname: Espinoza
authors.forename: Sonia
authors.initials: S
authors.lastname: Hassan
authors.forename: Francesca
authors.initials: F
authors.lastname: Gotsch
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Cecilia
authors.initials: C
authors.lastname: Avila
authors.forename: Offer
authors.initials: O
authors.lastname: Erez
authors.forename: Sam
authors.initials: S
authors.lastname: Edwin
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000378:metabolism*; D002821:Chorioamnionitis / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007752:Obstetric Labor, Premature / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D055815:Young Adult
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic