PMID- 10476693
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20041117
IS  - 1046-7408 (Print)
IS  - 1046-7408 (Linking)
VI  - 42
IP  - 2
DP  - 1999 Aug
TI  - The possible role of classical human leukocyte antigens in recurrent miscarriage.
PG  - 110-5
AB  - PROBLEM: If immunological factors play a role in the pathogenesis of recurrent 
      miscarriage (RM), it is likely that associations between alleles of classical 
      human leukocyte antigen (HLA) genes and RM exist. Our aim was to investigate 
      HLA-C alleles in RM couples and HLA-DR and -DQ polymorphism in women with 
      unexplained RM. METHOD OF STUDY: HLA-C alleles were investigated in 35 RM and 30 
      control couples and HLA-DR and -DQ allogenotypes were investigated in 234 RM 
      patients and 360 controls. All HLA investigations were undertaken by DNA based 
      methods. RESULTS: We found no difference between the RM and control couples in 
      the degree of paternal incompatibility for maternal HLA-C alleles and the 
      distribution of the two HLA-C supertypic specificities that are recognized 
      differently by p58 killer cell inhibitory receptor (KIR) positive natural killer 
      (NK) cells was similar in the two groups. In 97 women with at least four previous 
      miscarriages, significantly higher frequencies of the HLA-DR1,DQ5 and -DR3,DQ2 
      haplotypes were found compared with 360 controls (P < 0.05 after correction for 
      multiple comparisons). Among 94 RM patients followed prospectively, those with 
      HLA-DR1 and/or -DR3 had a 62% miscarriage rate compared with only 29% among those 
      without these alleles (P < 0.05). A large family study indicated that HLA-DR1 
      and/or -DR3 positive sisters and brothers' wives of probands with RM had an odds 
      ratio of 5.0 for miscarrying their pregnancies compared with corresponding 
      HLA-DR1 and -DR3 negative relatives. Finally, a meta-analysis of relevant studies 
      based on a MEDLINE search showed that HLA-DR1, -DR3, and -DR4 were significantly 
      increased in Caucasian women with RM. CONCLUSIONS: HLA-DR1, -DR3, and maybe -DR4 
      show association to RM in Caucasian women whereas no association to classical HLA 
      class I genes including HLA-C can be detected in RM couples. The mechanism by 
      which class II alleles confer susceptibility to RM might be by predisposing to 
      hypersecretion of certain cytokines, e.g., tumor necrosis factor (TNF)-alpha at 
      the feto-maternal interface.
FAU - Christiansen, O B
AU  - Christiansen OB
AD  - Department of Clinical Immunology, Aalborg Hospital, Denmark.
LA  - eng
PT  - Journal Article
PL  - Denmark
TA  - Am J Reprod Immunol
JT  - American journal of reproductive immunology (New York, N.Y. : 1989)
JID - 8912860
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - Abortion, Habitual/genetics/*immunology
MH  - Alleles
MH  - Female
MH  - HLA Antigens/genetics/*physiology
MH  - HLA-C Antigens/genetics/physiology
MH  - HLA-DQ Antigens/genetics/physiology
MH  - HLA-DR Antigens/genetics/physiology
MH  - Haplotypes
MH  - Humans
MH  - Pregnancy
EDAT- 1999/09/07 00:00
MHDA- 1999/09/07 00:01
CRDT- 1999/09/07 00:00
PHST- 1999/09/07 00:00 [pubmed]
PHST- 1999/09/07 00:01 [medline]
PHST- 1999/09/07 00:00 [entrez]
PST - ppublish
SO  - Am J Reprod Immunol. 1999 Aug;42(2):110-5.