Danish Medical Bulletin - No. 3. September 2004. Vol. 51 Page 295.

ABSTRACT OF PhD DISSERTATION

Immunologic and immunogenetic determinants
of recurrent miscarriage

Christina E. Kruse

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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.
E-mail: ckruse@dadlnet.dk

Dan Med Bull 2004;51:295.

ABSTRACT

The PhD dissertation is based on studies performed at the Department of Obstetrics and Gynaecology and the Department of Clinical Immunology, Aalborg Hospital, and the Department of Medical Microbiology and Immunology, University of Aarhus. The dissertation is based on three original publications.

The purpose of the study was to investigate the impact of the following suggested determinants of recurrent miscarriage (RM): 1) A low serum level of mannan-binding lectin (MBL), 2) Suggested susceptibility 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 frequency 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 pregnancy, compared to RM patients with normal s-MBL levels.

The second part of the study was a case-control study of the distribution of HLA-DR and -DQ alleles in 588 RM patients and 562 controls. The frequency of the HLA-DRB1*03 allele was significantly 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 pregnant 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 condition, 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.
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