HLA-G polymorphisms and molecule function--questions and more questions--a review

Area of Science:

• Immunogenetics
• Reproductive Immunology

Background:

• Human Leukocyte Antigen (HLA)-G is a non-classical HLA class I antigen primarily expressed on invasive trophoblast cells.
• It is hypothesized to mediate maternal-fetal tolerance and interacts with NK cells, presenting peptides and binding CD8.
• HLA-G exists in soluble and membrane-bound isoforms, generated via alternative splicing.

Purpose of the Study:

• To investigate the role of HLA-G in pregnancy, particularly in cases of recurrent spontaneous abortions.
• To analyze the implications of HLA-G variations, including the Null-allele G*0105N, on pregnancy outcomes.
• To systematically evaluate hypotheses regarding HLA-G function in vivo.

Main Methods:

• Analysis of HLA-G DNA sequence variations and allele definitions.
• Identification of individuals homozygous for the G*0105N Null-allele.
• Review of existing literature and hypotheses on HLA-G function.

Main Results:

• While essential positions for classical HLA-I function are conserved in HLA-G, polymorphic sites differ from highly variable sites in classical HLA.
• Two females with recurrent spontaneous abortions were identified as homozygous for the G*0105N Null-allele.
• These findings necessitate a re-evaluation of HLA-G's role in pregnancy.

Conclusions:

• The discovery of G*0105N Null-allele homozygosity in women with recurrent spontaneous abortions highlights the potential clinical significance of HLA-G variations.
• Further systematic research is required to elucidate the precise in vivo functions of HLA-G and its impact on reproductive success.