Reproductive Immunology

Marighoula Varla-Leftherioti, Marilyn Spyropoulou-Vlachou

Background

Reproductive Immunology studies have been performed in the framework of the past three Workshops (13th, 14th and 15th). First, it was investigatedwhether increased HLA sharing or HLA allele homozygosity between partners predisposed to repeated spontaneous abortion (RSA) (alloimmune or autoimmune abortions) and/or repeated unexplained implantation failures after IVF/ET (RIF). Then, the studies focused on the involvement of maternal KIR repertoire in embryo implantation and maintenance of pregnancy.

So far the results obtained in the Workshops oppose the suggestion that increased HLA sharing/homozygocity (even for specific alleles i.e. HLA-DQA1*05:05) predispose to RSA or RIF. However, the results suggested that: a) women with alloimmune abortions or implantation failures may possess a KIR repertoire characterized by the increased presence of activating receptors (14th Workshop, M. Varla-Leftherioti et al, Tissue Antigens 2007; 69 (s1):297-303), and b) a maternal-trophoblast  KIR2DL3-C1 combination (or lack of the KIR2DL1-C2 one) is also associated with implantation failure (15th Workshop, M. Varla-Leftherioti et al, Tissue Antigens 2010; 75 (6):668-72).

Goal:
Our suggestion for the 16th Workshop is to further investigate whether specific maternal KIR gene repertoire/haplotypes or maternal KIR– trophoblast HLA-C combinations are associated with increased risk for adverse reproductive outcome and/or pregnancy complications.

Research plan:

In order to achieve our goal we’ll work on the following subjects/material:

1. Couples with a history of RSA
2. Couples with a history of RIF
3. Couples with women having developed pre-eclampsia during pregnancy
4. Placental material from therapeutic pregnancy terminations (abortions)
5. Controls: i. Fertile couples (no abortion, implantation failure, preeclampsia), ii. Placental material from elective pregnancy terminations

Inclusion criteria for RSA and RIF couples*:

1. Childless couples with ≥ 3 RSA, couples with no more than one successful pregnancy and ≥2 consecutive RSAs, couples with <3 abortions, where histology / immuno-histology of the products of the abortions has revealed immune abnormalities.
2. Couples with repeated IVF/ET failures (women younger than 38 y, >5 E/T failures

* In all cases, other than immune aetiology of pregnancy failure, has to be excluded

Plan outline:

Stage I:
Identification of the centres and laboratories who are interested in participating. As it is essential to have well defined groups of sub-fertile couples, participants have to ensure that they can follow the protocol that will be given to them for the identification and the investigation of the couples.

Stage II:
After the selection of couples, DNA samples will be collected from all partners for HLA-C genomic high resolution typing. Women will be typed for KIR genes.

In case of placental material, DNA samples from decidua and trophoblast cells will be used for KIR and HLA-C genotyping respectively.

Typing results will be accepted by ASHI or EFI accredited laboratories. Laboratories with no accreditation will be accepted after successful typing of control DNA samples that will be provided.

Stage III:
According to the results of women’s KIR genotyping, KIR haplotypes will be defined by specific analysis and comparison will be performed between groups. KIR/HLA-C epitope matching will also be analyzed between groups.

Contacts:
Please let us know if you would like to participate in the workshop.  We will provide you with further information as the project proceeds.

Dr Marighoula Varla-Leftherioti
Department of Immunobiology, “Helena Venizelou” Maternity Hospital
2 Helen’s Venizelou sq.,
Athens 11521
Greece

Tel: 30-210-6453759,
Fax: 30-210-6402149,
E-mail: gr1bmdr [at] hol [dot] gr

Dr Marilyn Spyropoulou-Vlachou
Department of Immunology - Histocompatibility, “Alexandra” General Hospital of Athens
80 Vas. Sofias Ave
Athens 15128,
Greece

Tel/Fax: +30-2107799979,
E-mail: marilyn [at] ath [dot[ forthnet [dot] gr

Download a PDF of the ASHI 2011 Presentation - download PDF file.

Nov 10, 2011 Posted by Admin