title: Clinical chorioamnionitis is characterized by changes in the expression of the alarmin HMGB1 and one of its receptors, sRAGE.
abstract: OBJECTIVE
  High mobility group box-1 (HMGB1) protein is an alarmin, a normal cell constituent, which is released into the extracellular environment upon cellular stress/damage and capable of activating inflammation and tissue repair. The receptor for advanced glycation end products (RAGE) can bind HMGB1. RAGE, in turn, can induce the production of pro-inflammatory cytokines; this may be modulated by the soluble truncated forms of RAGE, including soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE). The objectives of this study were to determine whether: 1) clinical chorioamnionitis at term is associated with changes in amniotic fluid concentrations of HMGB1, sRAGE and esRAGE; and 2) the amniotic fluid concentration of HMGB1 changes with labor or as a function of gestational age.
  
  
  METHODS
  Amniotic fluid samples were collected from the following groups: 1) mid-trimester (n = 45); 2) term with (n = 48) and without labor (n = 22) without intra-amniotic infection; and 3) term with clinical chorioamnionitis (n = 46). Amniotic fluid concentrations of HMGB1, sRAGE and esRAGE concentrations were determined by ELISA.
  
  
  RESULTS
  1) the median amniotic fluid HMGB1 concentration was higher in patients at term with clinical chorioamnionitis than in those without this condition (clinical chorioamnionitis: median 3.8 ng/mL vs. term in labor: median 1.8 ng/mL, p = 0.007; and vs. term not in labor: median 1.1 ng/mL, p = 0.003); 2) in contrast, patients with clinical chorioamnionitis had a lower median sRAGE concentration than those without this condition (clinical chorioamnionitis: median 9.3 ng/mL vs. term in labor: median 18.6 ng/mL, p = 0.001; and vs. term not in labor median: 28.4 ng/mL, p < 0.001); 3) amniotic fluid concentrations of esRAGE did not significantly change in patients with clinical chorioamnionitis at term (clinical chorioamnionitis: median 5.4 ng/mL vs. term in labor: median 6.1 ng/mL, p = 0.9; and vs. term not in labor: median 9.5 ng/mL, p = 0.06); and 4) there was no significant difference in the median AF HMGB1 concentration between women at term in labor and those not in labor (p = 0.4) and between women in the mid-trimester and those at term not in labor (mid-trimester: median 1.5 ng/mL; p = 0.2).
  
  
  CONCLUSIONS
  An increase in the amniotic fluid HMGB1 concentration and a decrease in sRAGE were observed in clinical chorioamnionitis at term. This finding provides evidence that an alarmin, HMGB1, and one of its receptors, sRAGE, are engaged in the process of clinical chorioamnionitis at term. These changes are quite different from those observed in cases of intra-amniotic infection/inflammation in preterm gestations.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, Michigan 48201, USA. prbchiefstaff@med.wayne.edu
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Zeynep Alpay
authors.initials: ZA
authors.lastname: Savasan
authors.forename: Youssef
authors.initials: Y
authors.lastname: Hussein
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
mesh_terms: D000293:Adolescent; D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism*; D002821:Chorioamnionitis / Q000378:metabolism* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D005865:Gestational Age; D024243:HMGB1 Protein / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D009994:Osmolar Concentration; D011247:Pregnancy; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D012189:Retrospective Studies; D012995:Solubility; D047929:Term Birth / Q000378:metabolism; D055815:Young Adult
chemical_list: D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic