Я нашла хороший обзор на эту тему -
http://www.greenjournal.org/cgi/content/full/106/6/1393
Не уверена, есть ли эта статья в открытом доступе, поэтому приведу наиболее интересные выдержки.
The human leukocyte antigens (HLA) were first discovered in 1958. There are 2 classes of antigens. Class I antigens are expressed on the surface of almost all nucleated cells in the human body. They have been subclassified as HLA-A, HLA-B, and HLA-C. Class II antigens are expressed on the surface of immune cells and can be induced in some other cell types. These have been subclassified as HLA-DR, HLA-DQ, and HLA-DP. Human leukocyte antigens play a major role in the immune recognition of foreign proteins by binding short peptides and presenting them to T lymphocytes.
The 6 major genes encoding the HLA antigens are located in the major histocompatibility complex on chromosome 6. Alleles of these genes vary in their nucleotide sequence, resulting in different protein transcription products and subsequently the expression of different HLA antigens. Because an individual receives one chromosome from each of his/her parents, there is a 1 in 4 chance of 2 siblings in a particular family sharing the same HLA type. If 2 siblings share one common chromosome (50% chance), they are said to be haploidentical.
The HLA genes are the most polymorphic of any found in the human genome, with hundreds of alleles being identified to date at each locus (Table 1).8 New alleles are being continuously discovered. Identified alleles for HLA-A, -B, and -DRB1 alone would allow for over 45 billion combinations, 9 times the world's current population. There are 2 explanations for this. Many of these represent a null allele—a unique HLA antigen is not encoded by this nucleotide change. In addition, specific combinations of alleles occur together in a phenomenon known as linkage disequilibrium. This limits the number of HLA types that occur in the general population. However, HLA types vary considerably based on race and ethnicity.
There is no accepted definition of a match for hematopoietic transplantation. In general, a "6-of-6" antigen match refers to compatibility at the HLA-A, -B, and -DRB1 loci (identical genes would be present on both chromosomes). Typically, matches at the HLA-A and -B loci are performed through intermediate DNA resolution techniques, whereas the HLA-DRB1 match is performed using high-resolution molecular methods. Although there are 12 HLA loci that could potentially impact a hematopoietic transplant, many transplant centers additionally match for the HLA-C and -DQB1 loci (potential "10-of-10" antigen match).9
The National Marrow Donor Program is also affiliated with 15 umbilical cord blood banks and now contains an inventory in excess of 40,000 units. Nearly all patients will find a 4-of-6 match with the current inventory, while the majority will have a 5-of-6 match.10
A clear advantage of umbilical cord blood as a source of hematopoietic progenitor cell transplant is that a greater HLA mismatch is tolerated by the recipient than is the case with bone marrow transplant. Because of this tolerance of HLA incompatibility, the current recommendations for a "matched" cord unit include 2 or fewer HLA disparities at the HLA-A, -B, and -DRB1 loci (a minimum of a "4-of-6" match).
Residual T-lymphocytes in the hematopoietic progenitor cell product may also play a beneficial role in the patient with a hematopoietic malignancy; this is known as the graft-versus-leukemic effect.
The banking of umbilical cord blood for private use or public use is mired in emotion with very few facts. Private companies, particularly in the United States, have used direct patient advertising for recruitment, often using a promise of "biologic insurance" for the newborn. One company even offers a college savings plan as part of their package for storing cord stem cells.41 Important issues of future use, quality control, long-term availability, availability to those in need, and costs argue for public banking as a more practical approach to the use of umbilical cord blood.
In its committee opinion on this issue, the American College of Obstetricians and Gynecologists (ACOG) states "Parents should not be sold this service without a realistic assessment of their likelihood of return on their investment."42 Some private banks quote unrealistic odds for the future use of an umbilical cord blood unit stored in a private bank. One private bank cites a frequency of 1:27, with the future possibility of 50% of units ultimately being used.(43) Autologous umbilical cord blood cannot be used to treat inborn errors of metabolism because the genetic mutation is already present in the stem cells. In addition, some subtypes of leukemia are associated with chromosomal translocations that have been found in fetal blood.(44) For this reason, many pediatric hematologists will not use autologous stem cells to treat leukemia. In addition, the use of such cells would negate the beneficial graft-versus-leukemic effect (see above) that occurs with allogeneic stem cell transplants. This led Johnson(45) to suggest the that the chance of an individual using an autologous unit of cord blood is approximately 1:2,700.
The definition of a "quality" umbilical cord blood unit is still being refined. Initial procedures developed in the NIH COBLT trial called for a minimum unit volume at the time of the collection of 60 mL or a total nucleated cell count of 6 x 108 or greater if the volume was between 40 and 60 mL; units with volumes of less than 40 mL were discarded.46 Public banks also have numerous other exclusion criteria that are meant to assure quality. Many banks now use a minimum of 1 x 109 total nucleated cell count to define an adequate unit; this results in as many as 65–70% of units being discarded after initial collection (Joanne Kurtzberg, MD, Director, Carolinas Cord Blood Bank at Duke, personal communication, July 1, 2005). The collection of units for private banking is subject to the pressure of "our only chance to collect cells." Therefore, suboptimal units are often sent to the collection facility. At the time of the processing, the private bank will usually contact the parents to have them decide whether to store or discard the unit. Many decide to proceed with storage with very little knowledge that the unit could not be realistically used at a later date.
Because umbilical cord blood banking is in its infancy, issues with long-term availability have not arisen. Studies have shown long-term survival of stem cells in cord units for up to 15 years after initial freezing.47 Viability of cells after this time has not been substantiated. This, therefore, calls into question the use of autologous stem cells harvested at birth for regenerative medicine many decades later. In addition, private banks must continue to recruit new donors to remain financially viable. What is to happen to privately donated units if a company becomes insolvent?
The final argument for public banking involves the use of a human resource for the greater good of mankind. Public banks collect units from patients with a wide ethnic diversity. Many actually seek out certain ethnic groups that are underrepresented in the national bone marrow registry. Private banking allows those of means to collect stem cells while the less fortunate have no access to this valuable resource. Because of the economics of maintaining a public bank based on current use, many public banks have found it necessary to curtail or even eliminate collection activity (this includes an initial effort by the Red Cross to establish a cord blood bank).
All of these reasons have led many organizations and countries to take a stand against private banking. The American Academy of Pediatrics has suggested "...private storage of cord blood for biologic insurance is unwise."49 In Europe, the practice of private cord banking has been banned by law in Italy since 2002. The Royal College of Obstetricians and Gynaecologists states their position as "Routine directed commercial cord blood collection and stem cell storage cannot be recommended at the present time, because of the insufficient scientific base to support such practices...."50 The French National Consultative Ethics Committee's "...recommendation to decision makers is that they should encourage a considerable extension of cord public banks for essentially allogeneic purposes, rather than subscribing to the creation of private banks for strictly autologous purposes, the potential therapeutic usefulness of which is, as yet, in no way corroborated."51 Finally, in March of 2004, the European Group on Ethics in Science and New Technologies stated their position as follows: "The legitimacy of commercial cord blood banks for autologous use should be questioned as they sell a service which has presently no real use regarding therapeutic options. Thus, they promise more than they can deliver. The activities of such banks raise serious ethical criticisms."52
"If you thought that science was certain - well, that is just an error on your part." Richard Feynman
