Immunologic and immunogenetic determinants of recurrent miscarriage by boj84462



Immunologic and
immunogenetic determinants
of recurrent miscarriage
Christina E. Kruse

This PhD dissertation was accepted by the Faculty of Health Sciences of the
University of Aarhus, and defended on April 22, 2004.
Official opponents: Niels Grunnet, Peter Garred and Helle Meinertz Jensen.
Tutors: Jens Chr. Jensenius and Ole B. Christiansen.
Correspondence: Christina Kruse, Rolighedvej 6, DK-9400 Nørresundby.

Dan Med Bull 2004;51:295.

The PhD dissertation is based on studies performed at the Depart-
ment of Obstetrics and Gynaecology and the Department of Clinical
Immunology, Aalborg Hospital, and the Department of Medical
Microbiology and Immunology, University of Aarhus. The disserta-
tion is based on three original publications.
   The purpose of the study was to investigate the impact of the fol-
lowing suggested determinants of recurrent miscarriage (RM): 1) A
low serum level of mannan-binding lectin (MBL), 2) Suggested sus-
ceptibility HLA-DR and DQ alleles, and 3) A Th-1 biased cytokine
profile in pregnant RM patients.
   In the first part of the study a significantly higher frequency of
low serum level of MBL (<50ng/ml or <100 ng/ml) was found in
women with RM, compared to a healthy control group, and the fre-
quency of low s-MBL increased significantly with the number of
previous miscarriages. In a prospective study RM patients with low
s-MBL had a significantly higher miscarriage rate in their next preg-
nancy, compared to RM patients with normal s-MBL levels.
   The second part of the study was a case-control study of the dis-
tribution of HLA-DR and -DQ alleles in 588 RM patients and 562
controls. The frequency of the HLA-DRB1*03 allele was signifi-
cantly increased in RM patients, and the association between RM
and this allele was stronger in the subgroups of patients with at least
four miscarriages and in secondary RM patients.
   In the third part of the study the production of the Th1 cytokines
IL-2, INF-γ and TNF-α and the Th2 cytokines IL-4 and IL-10 from
stimulated peripheral lymphocytes was measured in serial blood
samples from pregnant RM patients and a single sample from preg-
nant controls. The serial measurements of cytokine production were
reproducible during first trimester of pregnancy in RM patients,
and the study could not confirm the previous finding of a Th1
biased cytokine profile in RM patients, compared to a Th2 biased
profile in normal pregnant women.
   In conclusion, idiopathic RM is probably a multifactorial condi-
tion, in which the immunological determinants low s-MBL and the
HLA-DRB1*03 allele contribute to the risk of repeated miscarriages.
Further studies are needed to identify other risk factors, which can
be valuable in clinical practice.

DANISH MEDICAL BULLETIN VOL.   51   NO.   3/AUGUST 2004                       295

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