title: H-Y antibody titers are increased in unexplained secondary recurrent miscarriage patients and associated with low male : female ratio in subsequent live births.
abstract: BACKGROUND
  The birth of a boy is significantly more common than a girl prior to secondary recurrent miscarriage (SRM) and is associated with a poorer chance of a subsequent live birth. Children born after SRM are more likely to be girls. High-titer antisera specific for male antigens (H-Y) have been shown to arrest development of male bovine embryos efficiently. We consequently questioned the role of H-Y antibodies in women with SRM.
  
  
  METHODS
  Serum samples from patients with unexplained SRM (n = 84), unexplained primary recurrent miscarriage (PRM) (n = 12) and healthy women (n = 37) were obtained. The samples were taken during pregnancy (gestational weeks 4-5) for 77 (80%) of the patients. Enzyme-linked immunosorbent assay was used to detect immunoglobulin G antibodies that specifically recognized any of the five recombinant H-Y proteins (EIF1AY, RPS4Y1, ZFY, DDX3Y and UTY) and their H-X homologs.
  
  
  RESULTS
  H-Y-specific antibodies were more frequent in SRM patients (46%) compared with female controls (19%, P = 0.004) and PRM patients (8%, P = 0.01). The presence of H-Y antibodies in early pregnancy was associated with a low male: female birth ratio among the subsequent live births, as only 12% of children born to H-Y antibody-positive patients were boys compared with 44% boys born to H-Y antibody negative patients (P = 0.03).
  
  
  CONCLUSIONS
  The high frequency of H-Y antibody-positive SRM patients and the association between the presence of these antibodies in early pregnancy and the low number of male offspring, suggest that maternal immune responses against H-Y antigens can cause pregnancy losses. Further exploring these mechanisms may increase our understanding of unexplained SRM.
authors.affiliation: The Fertility Clinic 4071, University Hospital Copenhagen, Blegdamsvej 9, Rigshospitalet, Copenhagen Ø, Denmark. henriette.svarre.nielsen@rh.regionh.dk
authors.forename: H S
authors.initials: HS
authors.lastname: Nielsen
authors.forename: F
authors.initials: F
authors.lastname: Wu
authors.forename: Z
authors.initials: Z
authors.lastname: Aghai
authors.forename: R
authors.initials: R
authors.lastname: Steffensen
authors.forename: A G
authors.initials: AG
authors.lastname: van Halteren
authors.forename: E
authors.initials: E
authors.lastname: Spierings
authors.forename: O B
authors.initials: OB
authors.lastname: Christiansen
authors.forename: D
authors.initials: D
authors.lastname: Miklos
authors.forename: E
authors.initials: E
authors.lastname: Goulmy
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007518:Isoantibodies / Q000032:analysis*; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D012744:Sex Ratio
chemical_list: D006182:H-Y Antigen; C051256:H-Y antibody; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies
references.citation: Immunol Today. 1993 May;14(5):203-8
references.pmid: 7686009
references.citation: J Immunol. 2007 May 1;178(9):5949-56
references.pmid: 17442979
references.citation: Hum Reprod. 2004 Dec;19(12):2946-51
references.pmid: 15513982
references.citation: Theriogenology. 2004 Dec;62(9):1569-76
references.pmid: 15511544
references.citation: Obstet Gynecol. 1993 Jul;82(1):132-8
references.pmid: 8515913
references.citation: Blood. 2001 Oct 1;98(7):2043-51
references.pmid: 11567988
references.citation: N Engl J Med. 2010 Apr 29;362(17):1586-96
references.pmid: 20335572
references.citation: Hum Reprod. 2001 Jan;16(1):102-106
references.pmid: 11139545
references.citation: Hum Mol Genet. 2009 May 1;18(9):1684-91
references.pmid: 19223392
references.citation: Blood. 2004 Jan 1;103(1):353-9
references.pmid: 14512314
references.citation: Mol Reprod Dev. 1993 Jan;34(1):25-32
references.pmid: 8418813
references.citation: Transplantation. 2008 Jul 15;86(1):75-81
references.pmid: 18622281
references.citation: Hematol J. 2001;2(6):363-70
references.pmid: 11920275
references.citation: Fertil Steril. 2008 Apr;89(4):907-11
references.pmid: 18222440
references.citation: Am J Reprod Immunol. 1996 Apr;35(4):352-9
references.pmid: 8739453
references.citation: Am J Obstet Gynecol. 2006 Jul;195(1):29-39
references.pmid: 16579915
references.citation: Aust N Z J Obstet Gynaecol. 2006 Aug;46(4):316-22
references.pmid: 16866793
references.citation: Am J Epidemiol. 2008 Feb 15;167(4):480-4
references.pmid: 18048378
references.citation: Am J Med Genet A. 2008 Jan 1;146A(1):66-70
references.pmid: 18074370
references.citation: Blood. 2005 Apr 1;105(7):2973-8
references.pmid: 15613541
references.citation: Aust N Z J Obstet Gynaecol. 2009 Dec;49(6):619-26
references.pmid: 20070710
references.citation: Hum Reprod. 2010 Jun;25(6):1543-52
references.pmid: 20395221
references.citation: Epidemiology. 2010 Jan;21(1):114-7
references.pmid: 19901840
references.citation: J Exp Med. 2006 Sep 4;203(9):2165-75
references.pmid: 16923853
references.citation: Hum Reprod Update. 2002 Jul-Aug;8(4):333-43
references.pmid: 12206468
references.citation: Proc Biol Sci. 2007 Dec 7;274(1628):2981-8
references.pmid: 17895226
references.citation: Placenta. 2010 Mar;31 Suppl:S33-9
references.pmid: 20004469
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10915-20
references.pmid: 17576931
references.citation: Arch Gynecol Obstet. 2005 Apr;271(4):350-4
references.pmid: 15221323
references.citation: Placenta. 2007 May-Jun;28(5-6):378-82
references.pmid: 16934327
references.citation: Biol Blood Marrow Transplant. 2006 Jul;12(7):758-69
references.pmid: 16785065
references.citation: J Clin Immunol. 2004 Jul;24(4):327-39
references.pmid: 15163889
references.citation: Hum Reprod. 2009 Jul;24(7):1754-7
references.pmid: 19357137
references.citation: Blood. 2004 Mar 1;103(5):1961-4
references.pmid: 14592836
references.citation: Br Med J. 1971 Jul 10;3(5766):90-2
references.pmid: 4996968
references.citation: J Immunol. 2000 Mar 1;164(5):2807-14
references.pmid: 10679124
references.citation: Am J Obstet Gynecol. 2005 Oct;193(4):1472-7
references.pmid: 16202742