For Who Can Be Used a CBU According to Immunological Compatibility?

3. What kind of tests are performed in order to check the immunological compatibility between the donor and recipient?

HLA typing is a special kind of test which is performed in order to check the immunological compatibility between the donor and recipient.

HLA genes have many possible variations, some of them having hundreds of identified versions (so called alleles). Each of such allele is given a particular number. Closely related alleles are categorized together as allele groups.

By HLA typing it is defined the set of HLA alleles and allele groups for both, the potential donor and recipient. Subsequently the results are compared to check the degree of similarity.    

Currently are used DNA-based methods, which vary according to resolution from low to high resolution.

Stem cells transplantation requires a high-resolution typing, such as Sequenced Based Typing (SBT). By applying this method are identified alleles of HLA-A, -B, -C, - DRB1, -DQB1 and -DPB1 for potential donor and recipient.

Bone marrow transplantation requires 10 from 10 alleles match (“perfect match”) or at least 8 from 10 alleles match.

Cord blood transplantation has the advantage of requiring a more flexible matching between donor and recipient.

It means that requires 6 from 6 alleles match (“perfect match”) or at least 4 from 6 alleles match.

This advantage translated into clinical practice means higher chances to find a potential donor of cord blood stem cells, if this source is eligible for patient’s needs.

HLA typing test usually is performed on blood drawn from a vein of the forearm.

4. The odds of the immunological compatibility between the members of a family.

The child inherits from each parent a set of 3 genes responsible for encoding HLA antigens, the immunological markers.

Their presence on the surface of the cells allows the immune system to recognize its own cells (self cells) and distinguish them from foreigner cells (non-self).

In respect of umbilical cord blood transplantation there are 3 important categories of HLA antigens (HLA-A; B, DR). For each of these, however, there are many subtypes, so called alleles  (e.g. for HLA-A antigen there are 59 different subtypes, for HLA-B 118 different subtypes and for HLA-DR 124 subtypes).

The multiple possibilities of combining these types and antigenic subtypes determine the great immunological heterogeneity found in the general population as well as the peculiarities of the various racial groups.

Unlike the general population, within a family there is a lower antigenic diversity due to the hereditary transmission of the HLA (major histocompatibility system) encoding genes, to offsprings.

This is the reason why in case of establishing the indication of an allogeneic transplant, the first option of verifying for a compatible donor is within the patient's family.

Both, the mother and the father transmits to each child a set of 3 genes (called haplotypes) from the two sets which they have in their own genome. (in the diagram below, mother has haplotypes 1 and 3 and father haplotypes 2 and 4).

Mathematically, there are 4 types of associations for the 2 sets of genes received from parents (in the scheme below the child A inherits 1 and 2 sets, the child B sets 1 and 4, the child C sets 3 and 2, the child  D sets 3 and 4).

The child E inherited sets 1 and 2, which are identical to those inherited by the child A. This means that between child A and child E there is a perfect match.

The chance of "perfect match" compatibility is 25% (1 in 4) for the children having the same parents.

Between siblings there is also 50% chance for a partial degree of only 50% immunological compatibility (in the scheme: child A has only set of genes identical with child B and C).

As a result of the Mendelian mode of inheritance of HLA antigens from each parent, between parents and their children there is only be a partial compatibility of 50% degree (or> 50% in particular situations when parents share at least 1 antigen).

50% partial compatibility, also called haploid compatibility may be acceptable only in certain particular cases of transplantation.

Immunological compatibility is one of the determinants of allogeneic transplantation evolution and outcome. It has a critical role in determining the tolerance degree of the donor cells toward the recipient and the clinical signs of the graft versus host disease.

Also, it influences the donated stem cells “homing” to bone marrow, the long term recovery of the blood cells forming process and the restoring of patient’s immune system.

In the absence of immunological compatibility, the immune cells from the graft would immediately identify the recipient body cells as “foreigners” (non self). Subsequently it would be triggered a fulminant process of immunological aggression and destruction, as response.

In conclusion,

  • Umbilical cord blood units stored in family banks can be used for autologous transplantation (self-use) or for allogeneic transplantation (use by a compatible related patient, especially by a sibling) only upon physician’s established indication.
  • The decision of indicating the use of an own cord blood unit or a sibling’s donated cord blood unit depends on several aspects. The most important are the following:
  • Type of treatment (standard stem cells transplantation or stem cell therapy as regenerative medicine)
  • Type of disease,
  • Particularity of the disease: staging, evolution, response to conservative treatment, and availability of other treatments.

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