Human Leukocyte Antigen (HLA) matching assesses the genetic compatibility between a patient and a potential donor, primarily for transplantation procedures. These molecules function as markers on the surface of most cells, serving as a biological identification tag for the immune system. This assessment predicts how the recipient’s immune system will react to foreign tissue, making it a foundational step to improve the chances of a successful outcome. A close match helps the body accept the new cells or organ rather than immediately recognizing them as a threat.
The Role of Human Leukocyte Antigens (HLA)
Human Leukocyte Antigens are proteins located on the surface of nearly all cells. These proteins are encoded by a cluster of genes known as the Major Histocompatibility Complex (MHC), the most genetically diverse system in humans. HLA molecules act as presenters, displaying small fragments of proteins, called antigens, to the immune system’s T-cells.
This presentation mechanism allows the immune system to distinguish “self” from “non-self.” If a cell is infected by a virus, the HLA molecule presents a piece of the viral protein, triggering cytotoxic T-cells to destroy the infected cell. The high variability (polymorphism) of HLA genes is a survival mechanism, ensuring a population can collectively recognize a wide range of pathogens.
The genetic diversity of HLA is immense, with over 37,000 different alleles identified, making finding a perfect match between two unrelated individuals highly challenging. These genes are inherited as a block (haplotype), with one coming from each parent. Consequently, a sibling who shares both haplotypes has a 25% chance of being an identical match, while a parent or child will always share one haplotype, resulting in a half-match.
Why Compatibility is Essential for Transplantation
When foreign tissue (such as a donated organ or stem cells) is introduced, the recipient’s immune system immediately scrutinizes the donor’s HLA markers. If the HLA types are significantly different, the immune system perceives the donated tissue as an invader, initiating a destructive immune response. This immunological attack is the primary reason compatibility testing is performed.
One major consequence of poor matching is graft rejection, which occurs when the recipient’s immune cells attack and destroy the transplanted organ or tissue. This T-cell-mediated rejection is directly linked to the recognition of foreign HLA molecules. A second, severe complication occurs specifically in hematopoietic stem cell transplants, where the donor’s immune cells are transferred along with the stem cells.
This complication is called Graft-versus-Host Disease (GVHD), where the donated immune cells (the graft) recognize the recipient (the host) as foreign. The donor T-cells attack the recipient’s tissues, which can be life-threatening and affect organs like the skin, liver, and gastrointestinal tract. Minimizing HLA disparity is the most robust factor in predicting a successful outcome and reducing the risk of both graft rejection and GVHD.
How HLA Typing and Matching Are Performed
The process of determining compatibility begins with HLA typing, a genetic test to identify the specific HLA markers in both the patient and the potential donor. Modern HLA typing primarily relies on DNA-based molecular analysis techniques for high resolution. The sample (typically blood or a cheek swab) is sent to a specialized laboratory to extract the DNA.
The most common method involves Polymerase Chain Reaction (PCR), which amplifies the DNA segments encoding the HLA molecules. This amplified DNA is then analyzed using methods like Sequence-Specific Oligonucleotide Probing (SSOP) or Next-Generation Sequencing (NGS) to determine the exact sequence of the HLA genes. NGS is often used due to its ability to simultaneously sequence many fragments and define the specific alleles (variant forms of the gene).
Matching is focused on specific HLA loci, which are grouped into Class I (HLA-A, HLA-B, and HLA-C) and Class II (HLA-DR, HLA-DQ, and HLA-DP). A typical compatibility score is determined by comparing the alleles at these six main loci. Since two alleles are counted for each locus (one from each parent), a perfect match results in a 12/12 score. For many procedures, the score is often reported based on the HLA-A, -B, -C, and -DRB1 loci, aiming for a 6/6 or 8/8 match as the ideal scenario.
The goal of HLA matching is to achieve the highest possible number of shared alleles between the donor and recipient. A higher match is strongly associated with a reduced risk of complications and improved long-term graft survival. Even a single mismatch at certain loci, such as HLA-A, -B, -C, or -DRB1, can significantly increase the risk of severe GVHD and mortality in stem cell transplants.
Clinical Applications of HLA Compatibility
The required stringency of HLA matching differs depending on the type of transplant. Hematopoietic Stem Cell Transplants (HSCT), including bone marrow transplants, demand the most precise matching because they involve transferring immune cells. A near-perfect match, such as 8/8 or 10/10 at the major loci, is sought for unrelated donors to minimize the risk of severe GVHD.
Solid Organ Transplants (such as kidney or heart transplants) benefit from HLA matching but tolerate a less stringent match. While compatibility improves long-term outcomes, the successful use of immunosuppressive drugs allows these transplants to proceed even with mismatches. Matching in solid organ transplants primarily prevents the recipient’s immune system from rapidly destroying the organ.
HLA typing is a prerequisite for listing patients and donors on national and international registries to find unrelated compatible donors. The use of cord blood as a source of stem cells is advantageous because the cells are less mature and may allow for a less stringent match, sometimes requiring only a 4/6 match.