Preimplantation HLA Typing

Abstract

It has been more than ten years since the first Human Leukocyte Antigen (HLA) matching for Fanconi anemia was reported, allowing successful haemopoietic reconstitution in affected sibling by transplantation of stem cells obtained from HLA-matched offspring (Verlinsky et al., 2000; Verlinsky et al., 2001). Preimplantation Genetic Diagnosis (PGD) in combination with HLA matching is being used to detect a particular gene mutation in an unaffected child who can be an HLA donor for its’ sibling. HLA typing without mutation analysis has also been used for acquired diseases (Verlinsky et al., 2004), such as acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), which require allogenic haemopoietic stem cell transplantation (HSCT) from an HLA identical donor for the cure of the disease. Stem cells in the cord blood from an HLA identical sibling can be used with a much higher success rate than a transplant from alternative donors (Gaziev et al., 2000; Orofino et al., 2003) and are therefore of great therapeutic value for hematopoietic and other life-threatening diseases (Fiorentino et al., 2006; Kahraman et al., 2004, 2007; Verlinsky et al., 2001, 2004; Van de Velde et al., 2004, 2009). In particular for blood-borne disorders, hematopoietic stem cells (HSC) from HLA-identical siblings provide the highest success rate and current results indicate that about 90% of the cases can be cured successfully after HSC transplantation (Gaziev et al., 2005). Use of cord blood as a stem cell source also results in reduced incidence of graft rejection and other serious complications associated with bone marrow transplantation. However, in most cases a suitable donor cannot be found in the family, and due to a small number of children per family, only one third of patients are able to find an HLA-identical sibling (Costeas, 2004). The probability of having an unaffected child who may also be an HLA match for an affected sibling is only one in five; these families often went through multiple cycles of pregnancy before conceiving an unaffected HLA match. In the remaining patients the only resort is the identification of a matched unrelated donor. However, the probability of finding an HLA matched unrelated donor cord blood from the cord blood units is extremely low. Therefore PGD is a much more attractive option, with this technique, sufficient number of embryos may be tested at one time, increasing the chances of identifying an appropriate match. More than 2000 healthy children have already been born after PGD and the expanding indications include chromosomal abnormalities, single gene disorders, HLA tissue typing of the embryos, predisposition of adult onset disorders, translocations and cancer predispositions (Simpson 2001; Kuliev et al., 2004; Fiorentino et al., 2004; 2006; Kahraman et al., 2005; 2007; Van de Velde et al., 2004; Kokkali et al., 2007). In fact PGD can be carried out