The Human Leukocyte Antigen (HLA) typing test is a specialized diagnostic procedure used to identify specific protein markers located on the surface of most cells in the body. These proteins are encoded by a set of genes within the Major Histocompatibility Complex (MHC), and their unique combination acts as an individual’s biological fingerprint. The primary application of HLA typing is to determine the genetic compatibility between a patient and a donor before solid organ or hematopoietic stem cell transplantation. This assessment minimizes the risk of the recipient’s immune system recognizing the transplanted material as foreign and attacking it.
The Role of Human Leukocyte Antigens
Human Leukocyte Antigens are cell-surface proteins integral to the function of the immune system, acting as molecular tags that communicate self versus non-self status. Their main job is to present small protein pieces, called peptides, to T-cells, the immune system’s primary defenders. By presenting these peptides, HLA molecules allow the immune system to recognize and eliminate infected or abnormal cells.
HLA genes are the most diverse and variable set of genes in the human genome, a characteristic called polymorphism. This high variability means millions of unique combinations exist, making a perfect match between two unrelated individuals rare. The HLA system is divided into two main categories: Class I molecules (HLA-A, HLA-B, and HLA-C) are found on nearly all nucleated cells. Class II molecules (HLA-DR, HLA-DQ, and HLA-DP) are primarily found on specialized immune cells, such as B-cells and macrophages.
Since every person inherits half of their HLA genes from each parent, siblings have the highest probability—about a one in four chance—of being a full HLA match. Parents and children always share half of their HLA markers, representing a half-match, also known as haploidentical. This inherited profile determines the success or failure of a transplant.
Primary Reasons for HLA Testing
The most common reason for performing an HLA typing test is to facilitate safe transplantation, including solid organs (kidneys, hearts, lungs) and hematopoietic stem cells. A close match lowers the risk of the recipient rejecting the new tissue or the transplanted immune cells attacking the recipient’s body. Matching requirements are stricter for stem cell transplants than for solid organ transplants because hematopoietic stem cells contain immune cells that can cause graft-versus-host disease (GVHD).
HLA testing is also used for the diagnosis or risk assessment of certain autoimmune diseases. The presence of specific HLA genes is associated with conditions where the immune system mistakenly attacks the body’s own tissues. For instance, the HLA-B27 allele is found in a large percentage of individuals with Ankylosing Spondylitis and related forms of arthritis.
The test is applied in specialized blood transfusions, particularly for patients refractory to standard platelet transfusions. These patients may have developed antibodies against common HLA markers, requiring a search for a compatible platelet product. In a non-medical context, the genetic nature of the HLA system means it can also be used in forensic science and paternity testing.
The Testing Process and Methodology
The HLA typing process begins with collecting a biological sample, typically a blood sample or a cheek swab, which contains the necessary genetic material. The sample is sent to a specialized laboratory where DNA is extracted from the white blood cells. Modern HLA typing relies almost entirely on molecular, DNA-based techniques, offering much higher precision than older methods.
Historically, HLA compatibility was determined using serological methods, such as the complement-dependent cytotoxicity (CDC) assay, which identified antigens by observing the reaction of cells with known antibodies. The current standard is high-resolution molecular typing, which directly analyzes the DNA sequence of the HLA genes. Techniques like Polymerase Chain Reaction (PCR) are used to amplify specific regions of the HLA genes.
Following amplification, methods such as Sequence-Based Typing (SBT) or Next-Generation Sequencing (NGS) are employed to read the exact order of nucleotides in the HLA genes. NGS is the most advanced technique, enabling labs to simultaneously sequence multiple HLA genes with exceptional accuracy and speed. This high-resolution approach allows for the distinction of alleles that differ by only a single nucleotide, necessary for the most accurate matching.
Understanding HLA Match Results
The final results of an HLA typing test are reported using a standardized nomenclature reflecting the specific alleles found at each HLA locus. For hematopoietic stem cell transplants, the gold standard involves matching the patient and donor at five major loci: HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1. Since two alleles are inherited for each locus, this is commonly reported as a 10/10 match if all alleles are identical at high resolution.
Achieving a 10/10 match with an unrelated donor is the ideal outcome, associated with the lowest risk of complications like graft-versus-host disease (GVHD) and transplant rejection. A single mismatch (9/10 score) may be acceptable, but it carries a higher risk of adverse outcomes, particularly if the mismatch is at the HLA-A, -B, -C, or -DRB1 loci. For solid organ transplants, a match at fewer loci (often HLA-A, -B, and -DR) is considered acceptable due to better post-transplant immunosuppressive medications.
When a fully matched donor is not available, transplant teams may consider a haploidentical transplant, which uses a donor (usually a parent or child) who is a half-match (5/10). Although this option involves a greater degree of mismatch, advances in post-transplant immunosuppression have made this a viable alternative for patients needing a transplant urgently. The interpretation of the match score directly influences the choice of donor and the subsequent medical management required to prevent rejection.