Tissue typing, also known as histocompatibility testing, is a laboratory procedure used to determine the biological compatibility between a tissue donor and a recipient. This testing is a foundational step in modern medicine, particularly in scenarios where foreign material is introduced into the body. A successful match predicts the likelihood that the recipient’s immune system will accept the transplanted tissue or organ.
The Biological Basis of Tissue Typing
The Human Leukocyte Antigens (HLA) system is a gene complex located on chromosome 6 and represents the human version of the Major Histocompatibility Complex (MHC). HLA molecules are proteins expressed on the surface of most cells, acting as a unique molecular barcode for the immune system.
The primary function of these surface proteins is to help the immune system distinguish between “self” and “non-self” materials. They achieve this by presenting small pieces of protein, called antigens, to immune cells like T lymphocytes. When an HLA molecule displays a fragment of a foreign invader, it triggers an immune response.
HLA molecules are divided into Class I and Class II. Class I molecules are found on nearly all nucleated cells and present peptides derived from proteins made inside the cell. Class II molecules are primarily found on specialized immune cells, such as B cells and macrophages, and present peptides from foreign material encountered outside the cell. The genes encoding HLA are the most genetically variable in the human genome, meaning tens of thousands of different HLA alleles exist, making an exact match between two unrelated individuals highly improbable.
Clinical Necessity of Tissue Typing
Tissue typing is performed to minimize the risk of a recipient’s immune system attacking transplanted material. When the HLA markers on a donor organ do not match, the immune system perceives the new tissue as foreign. A closer HLA match significantly reduces the intensity of this rejection response and can decrease immunosuppressive drugs.
The requirement for a close match is especially strict in hematopoietic stem cell transplantation, commonly known as bone marrow transplantation. This procedure introduces donor immune cells into the recipient’s body, unlike solid organ transplants. If these new immune cells recognize the recipient’s tissues as foreign, they can attack the body in a severe complication called graft-versus-host disease (GVHD). Matching key HLA loci, such as HLA-A, HLA-B, HLA-C, and HLA-DRB1, is highly prioritized in this context.
Tissue typing also has a role beyond transplantation, as certain HLA types are associated with an altered risk for developing autoimmune disorders. For instance, the presence of the HLA-B27 allele is strongly linked to the inflammatory condition ankylosing spondylitis. Similarly, the HLA-DR2 type has been associated with multiple sclerosis and narcolepsy. This association provides insight into the genetic factors that influence immune-mediated diseases.
Current Methods for Tissue Typing
Historically, laboratories relied on serological testing, which involved mixing a person’s lymphocytes with panels of known antibodies. If an antibody bound to the HLA protein on the cell surface, a reaction would occur, allowing scientists to infer the person’s HLA type. This method was fast and inexpensive but offered low resolution, meaning it could not distinguish between subtle differences in the HLA structure.
Modern tissue typing focuses on analyzing the DNA itself, offering far greater precision and resolution. The Polymerase Chain Reaction (PCR) is a foundational technique, used to amplify millions of copies of the specific HLA gene segments. Sequence-Based Typing (SBT) is a high-resolution molecular method that uses PCR to amplify the DNA, followed by Sanger sequencing of the resulting product. By reading the exact nucleotide sequence of the HLA genes, SBT can identify specific alleles.
The most advanced method is Next-Generation Sequencing (NGS), which provides the highest-resolution HLA typing available. NGS is a high-throughput technology that can sequence entire HLA genes simultaneously, offering complete coverage of the highly polymorphic regions. This capability is important for resolving complex or ambiguous results and for identifying newly discovered alleles. The high-resolution results from NGS allow for the most precise donor-recipient matching, improving long-term transplant success, especially in stem cell transplantation.