title: Unexplained fetal death has a biological signature of maternal anti-fetal rejection: chronic chorioamnionitis and alloimmune anti-human leucocyte antigen antibodies.
abstract: OBJECTIVE
  Chronic chorioamnionitis is a histological manifestation of maternal anti-fetal cellular rejection. As failure of graft survival is the most catastrophic event in organ transplantation, we hypothesized that fetal death could be a consequence of maternal rejection. The aim of this study was to assess whether there is evidence of cellular and antibody-mediated rejection in fetal death.
  
  
  RESULTS
  Placental histology was reviewed for the presence of chronic chorioamnionitis in unexplained preterm fetal death (n=30) and preterm live birth (n=103). Amniotic fluid CXCL10 concentrations were measured with a specific immunoassay. Chronic chorioamnionitis was more frequent in fetal death than in live birth (60.0% versus 37.9%; P<0.05) and fetal death had a higher median amniotic fluid CXCL10 concentration than live birth (2.0 versus 1.8 ng/ml, P<0.05), after adjusting for gestational age at amniocentesis. Maternal anti-human leucocyte antigen class II panel-reactive seropositivity determined by flow cytometry was higher in fetal death compared to live birth (35.7% versus 10.9%; P<0.05).
  
  
  CONCLUSIONS
  Chronic chorioamnionitis is a common pathologic feature in unexplained preterm fetal death. This novel finding suggests that cellular and antibody-mediated anti-fetal rejection of the mother is associated with fetal death (graft failure) in human pregnancy.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, USA.
authors.forename: JoonHo
authors.initials: J
authors.lastname: Lee
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Faisal
authors.initials: F
authors.lastname: Qureshi
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jacques
authors.forename: Wonsuk
authors.initials: W
authors.lastname: Yoo
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Pooja
authors.initials: P
authors.lastname: Mittal
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000276:immunology; D002821:Chorioamnionitis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005313:Fetal Death / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D011247:Pregnancy; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D054357:Chemokine CXCL10; D006680:HLA Antigens
references.citation: Transplantation. 2005 May 15;79(9):1215-20
references.pmid: 15880073
references.citation: J Heart Lung Transplant. 2001 Feb;20(2):205
references.pmid: 11250368
references.citation: Int J Gynecol Pathol. 1991;10(3):217-29
references.pmid: 1917272
references.citation: Obstet Gynecol. 2010 Aug;116(2 Pt 1):254-260
references.pmid: 20664383
references.citation: Eur J Immunol. 2007 Jul;37(7):1924-37
references.pmid: 17549736
references.citation: J Perinat Med. 2005;33(4):306-13
references.pmid: 16207115
references.citation: Kidney Int. 2006 May;69(9):1683-90
references.pmid: 16572110
references.citation: Circ Res. 2006 Mar 17;98(5):617-25
references.pmid: 16484616
references.citation: Hum Pathol. 1998 Dec;29(12):1457-61
references.pmid: 9865833
references.citation: BMJ. 2005 Nov 12;331(7525):1113-7
references.pmid: 16236774
references.citation: Lab Invest. 2001 Mar;81(3):409-18
references.pmid: 11310833
references.citation: Eur J Immunol. 1998 Nov;28(11):3696-705
references.pmid: 9842912
references.citation: Transplantation. 2007 Mar 27;83(6):727-33
references.pmid: 17414705
references.citation: Pediatr Dev Pathol. 2004 Sep-Oct;7(5):443-52
references.pmid: 15547768
references.citation: J Matern Fetal Neonatal Med. 2007 Jul;20(7):495-507
references.pmid: 17674262
references.citation: J Matern Fetal Neonatal Med. 2010 Dec;23(12):1384-99
references.pmid: 20459337
references.citation: Ann N Y Acad Sci. 2009 Sep;1173:310-7
references.pmid: 19758167
references.citation: Blood Rev. 2002 Mar;16(1):69-72
references.pmid: 11914000
references.citation: Tissue Antigens. 1996 Mar;47(3):206-11
references.pmid: 8740770
references.citation: Am J Transplant. 2004 Sep;4(9):1466-74
references.pmid: 15307834
references.citation: Semin Fetal Neonatal Med. 2008 Aug;13(4):207-14
references.pmid: 18396474
references.citation: Placenta. 2005 Apr;26 Suppl A:S114-7
references.pmid: 15837060
references.citation: Am J Obstet Gynecol. 2005 Dec;193(6):1923-35
references.pmid: 16325593
references.citation: Placenta. 2008 Jan;29(1):71-80
references.pmid: 17963842
references.citation: J Perinat Med. 2005;33(4):296-305
references.pmid: 16207114
references.citation: Blood. 1964 May;23:621-46
references.pmid: 14142502
references.citation: Obstet Gynecol. 2009 Oct;114(4):901-914
references.pmid: 19888051
references.citation: Obstet Gynecol. 2009 Oct;114(4):809-817
references.pmid: 19888039
references.citation: Mod Pathol. 2010 Jul;23(7):1000-11
references.pmid: 20348884
references.citation: Lancet. 2010 Apr 24;375(9724):1482-90
references.pmid: 20223514
references.citation: Transfusion. 1990 May;30(4):344-57
references.pmid: 2190367
references.citation: J Reprod Immunol. 2010 Dec;87(1-2):67-73
references.pmid: 20605049
references.citation: J Exp Med. 2006 Sep 4;203(9):2165-75
references.pmid: 16923853
references.citation: Arch Gynecol Obstet. 2011 Feb;283(2):231-41
references.pmid: 20052483
references.citation: Eur J Obstet Gynecol Reprod Biol. 2008 Feb;136(2):155-9
references.pmid: 17459562
references.citation: Am J Obstet Gynecol. 2005 Jan;192(1):264-71
references.pmid: 15672035
references.citation: Pediatr Dev Pathol. 2003 Sep-Oct;6(5):435-48
references.pmid: 14708737
references.citation: Pediatr Dev Pathol. 2004 May-Jun;7(3):237-49
references.pmid: 15022063
references.citation: J Clin Invest. 2001 Jan;107(1):53-63
references.pmid: 11134180
references.citation: Am J Reprod Immunol. 2010 Apr 1;63(4):318-30
references.pmid: 20163401
references.citation: J Steroid Biochem Mol Biol. 1994 Jun;49(2-3):107-21
references.pmid: 8031707
references.citation: Hum Pathol. 2007 Oct;38(10):1439-46
references.pmid: 17889674
references.citation: Transplantation. 2009 Jan 27;87(2):249-55
references.pmid: 19155980
references.citation: J Cell Sci. 2009 Jun 15;122(Pt 12):2064-77
references.pmid: 19470579
references.citation: J Immunol. 2009 Mar 15;182(6):3919-27
references.pmid: 19265171
references.citation: Curr Opin Pharmacol. 2009 Aug;9(4):462-9
references.pmid: 19570712
references.citation: Lancet. 2006 May 6;367(9521):1487-94
references.pmid: 16679161
references.citation: Histopathology. 2008 Mar;52(4):457-64
references.pmid: 18315598
references.citation: Cell Immunol. 2010;260(2):83-91
references.pmid: 19875106
references.citation: Hum Immunol. 2001 Mar;62(3):201-7
references.pmid: 11250037
references.citation: J Exp Med. 2003 Jun 2;197(11):1537-49
references.pmid: 12782716
references.citation: J Reprod Immunol. 2000 Feb;46(1):51-7
references.pmid: 10708244