HLA genetic testing identifies specific variations, or alleles, within an individual’s Human Leukocyte Antigen (HLA) genes. This information is used in personalized medicine, where treatments and strategies are tailored to an individual’s genetic makeup.
Understanding Human Leukocyte Antigens
Human Leukocyte Antigens (HLAs) are proteins located on the surface of most cells in the body, with the exception of red blood cells. These proteins are a part of the immune system, helping it differentiate between the body’s own cells and foreign invaders such as viruses and bacteria. This distinction process ensures that foreign cells trigger an immune response.
The genes responsible for HLA proteins are located on chromosome 6, specifically within a region called the Major Histocompatibility Complex (MHC). The HLA system is highly polymorphic, meaning there are many different alleles or variations among individuals. This extensive variability allows the immune system to recognize and respond to a wide array of pathogens.
HLA molecules are divided into two main classes: Class I and Class II. Class I HLA molecules (HLA-A, HLA-B, and HLA-C) are found on the surface of nearly all nucleated cells and present peptides that originate from inside the cell, such as fragments from viruses. These presented peptides signal to cytotoxic T-cells (CD8+ T cells) to destroy infected or abnormal cells.
Class II HLA molecules (HLA-DP, HLA-DM, HLA-DO, HLA-DQ, and HLA-DR) are primarily found on specialized immune cells, known as antigen-presenting cells, including B cells, macrophages, and dendritic cells. These molecules present antigens that come from outside the cell, such as bacterial or fungal components, to helper T-cells (CD4+ T cells), which then coordinate a broader immune response.
Key Reasons for HLA Testing
HLA genetic testing serves various medical and scientific purposes, primarily due to the immune system’s reliance on these antigens for self-recognition and foreign detection. One of the primary applications is in organ and bone marrow transplantation. Matching HLA types between a donor and recipient is important to reduce the likelihood of the recipient’s immune system rejecting the transplanted organ or tissue. A closer HLA match correlates with a lower risk of rejection and improved long-term survival of the transplanted graft, as seen in kidney transplant recipients with HLA-identical siblings. In hematopoietic stem cell transplantation (HSCT), HLA matching helps prevent both graft rejection and graft-versus-host disease (GVHD).
Certain HLA types are linked to an increased susceptibility to specific autoimmune diseases, where the immune system mistakenly attacks the body’s own cells. For example, the HLA-B27 allele is strongly associated with ankylosing spondylitis, a form of arthritis affecting the spine. HLA-DQ2 and HLA-DQ8 alleles are linked to celiac disease, an autoimmune disorder triggered by gluten. HLA-DR3 and HLA-DR4 alleles are considered risk factors for Type 1 Diabetes, and HLA-DR1 and DR4 types are associated with rheumatoid arthritis. An association with an HLA type indicates an increased risk, not a definitive diagnosis, as other genetic and environmental factors are also involved.
Some HLA types can predict adverse reactions to certain medications, a field known as pharmacogenomics. For instance, individuals carrying the HLA-B5701 allele have an increased risk of developing a severe hypersensitivity reaction to abacavir, an antiretroviral drug used in HIV treatment. This reaction can include symptoms like fever, rash, and gastrointestinal issues. Screening for HLA-B5701 is recommended before starting abacavir therapy to avoid severe reactions.
HLA typing has also been used in paternity testing and forensic investigations. Since HLA antigens are inherited, specific HLA types in a child must be traceable to either parent, allowing for paternity probability calculations or exclusion. While once a significant tool, more advanced DNA-based paternity tests have made HLA testing less common for this purpose.
How HLA Testing is Performed
HLA genetic testing begins with the collection of a biological sample. This involves a blood draw from a vein in the arm, or sometimes a cheek swab. The collected sample is then sent to a specialized laboratory for analysis.
In the laboratory, DNA is isolated from the cells in the sample. Molecular biology techniques analyze the HLA genes, including Polymerase Chain Reaction (PCR)-based methods that amplify specific regions for detailed analysis. Next-generation sequencing (NGS) is also widely used, providing comprehensive information by sequencing large sections of the genome. These methods allow for high-resolution HLA typing, which is important for precise matching. Results are available within a few weeks, depending on the tests performed and the laboratory’s processing time.
Interpreting Your HLA Test Results
The results of an HLA test present specific HLA alleles or types, often denoted by a combination of letters and numbers (e.g., HLA-A02:01). These results are complex and require interpretation by a healthcare professional, who considers them within the context of an individual’s medical history and the reason for testing.
In the context of transplantation, HLA test results indicate the degree of compatibility between a donor and recipient. A “match” refers to the number of shared HLA molecules, with a higher number correlating with a better match and a reduced risk of transplant rejection. For instance, a 10/10 or 12/12 match at key HLA loci is often considered optimal for unrelated donor hematopoietic stem cell transplantation. Even partial matches can be acceptable, and research continues to identify “permissible mismatches” that may still lead to successful outcomes.
For disease association, the presence of certain HLA alleles indicates an increased genetic predisposition or risk for specific conditions, not a definitive diagnosis. Healthcare professionals use these results as part of a larger clinical picture, considering other diagnostic tests and the patient’s symptoms before making a diagnosis or treatment plan. Genetic counseling can also be helpful to understand the implications of these results for personal health and family planning.