HLA-G Testing
Summary
The major
histocompatability complex (MHC), well known for its role in the
regulation of cell-cell interaction in the immune response, also
influences reproductive success. The MHC affects a variety of reproductive
parameters including spontaneous abortion, protection of fetus from attack
by the maternal immune system and regulation of preimplantation embryo
growth and survival. One gene in the MHC that has special attention with
respect to reproduction is the class I gene HLA-G. It has been detected on
the surface of some human oocytes, preimplantation embryos and placental
cells. In addition, HLA-G:
1. binds peptides leading to antiviral
function
2. contributes to immunosurveillance by interacting
with T cell receptor inducing T cell tolerance and apoptosis of activated
cytotoxic T cells
3. modulates secretion of cytokines (IL1, IL3,
IL10 and TNFα) by binding to NK cell receptors
4. displays
angiogenic functions during gestation (HLA-G expression disappears in
pre-eclampsia)
The HLA gene encodes multiple isoforms that fulfill
a variety of functions, presumably to ensure survival of the allogenic
fetus. Mutations in the HLA gene could interfere with these vital
processes, resulting in pregnancy loss. To date, at least four different
mutations that are associated with spontaneous abortion have been
identified. These are HLA-G0104, HLA-G0105N, HLA-G01013 and -725C/G
promoter polymorphism. The 0104 alleles (0104 and 0104b) have an amino
acid substitution (Leu110Ile). The 0105N mutation is a deletion of
nucleotide 1597 ©/amino acid 130. The 01013 allele is a silent mutation.
Fetal loss rates are higher when even only one parent carries the -725G
allele.
Indication for Testing
All couples
experiencing recurrent pregnancy loss should have both partners tested for
HLA-G gene mutations.
Detection Method
HLA-G mutations are tested
by DNA sequencing for the presence of 0105N and -725C/G.
Interpretation of results
Results are reported as
mutations present or absent.
Specimen Collection, Handling and Shipping
Requirements
- Collect a sample DNA with a buccal swab.
- Ship at room temperature in prepaid FedEx mailer overnight, next day
delivery.
Turn Around Time
Processing of specimens
begins immediately upon receipt at our facilities. Results are routinely
available within 10 to 14 days and are initially faxed, then mailed to the
requesting physician.
Cost
Included in our test are specimen
collection and shipping materials, shipping charges, telephone and written
reports as well as consultations with the referring physicians. Please
call 1-877-737-7652 for pricing information.
References
Ober C et al. Variation in the
HLA-G promoter region influences miscarriage rates. Am J Hum Genet
2003;72:1425-1435.
Le Bouteiller P. The functionality of HLA-G is emerging. Immunol Rev
1999;167:233-244.
Werner CM, Brenner CA. Genetic regulation of preimplantation embryo
survival. Curr Topics in Develop Biol 2001;52:151-192.
Ober C. The Meeting of the American Society for Reproductive Medicine,
San Antonio, Texas, October, 2003.
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