Human Leukocyte Antigen (HLA) antibodies are specialized components of the immune system designed to recognize and neutralize foreign substances. These antibodies specifically target Human Leukocyte Antigens, which are proteins found on the surface of almost all nucleated cells throughout the body. Understanding these antibodies is important because they represent the body’s immunological memory of prior exposure to non-self tissues. They are not typically present in a healthy individual unless that person has been exposed to foreign cells that trigger an immune response.
The Role of Human Leukocyte Antigens
The Human Leukocyte Antigens are a group of cell-surface proteins often referred to as the Major Histocompatibility Complex (MHC) in other species. These proteins reside on the surface of white blood cells and most other cells, acting like unique identification tags for the immune system. Their primary biological function is surveillance, distinguishing between the body’s own cells and foreign invaders. HLAs are highly polymorphic, meaning there are numerous variants of these genes within the human population, ensuring that each person possesses a nearly unique set of these markers. This genetic diversity creates challenges in medical procedures involving tissue transfer, as the immune system sets the stage for rejection if a mismatch occurs.
Formation and Types of HLA Antibodies
HLA antibodies develop when an individual’s immune system is exposed to foreign HLA proteins, a process known as alloimmunization or sensitization. There are three main ways this exposure can occur, all involving the transfer of cells containing non-self HLA markers. Sensitization commonly occurs through pregnancy, where a mother may be exposed to paternal HLAs, or through multiple blood transfusions containing leukocytes. The most direct cause is a prior organ or tissue transplantation, where the recipient’s body has already mounted an immune response against mismatched donor tissue.
Once formed, these specialized antibodies, which are typically Immunoglobulin G (IgG) molecules, remain in the circulatory system. HLA antibodies are broadly categorized into Class I and Class II types, corresponding to the two main types of HLA antigens they target. Class I antibodies target HLA-A, -B, and -C antigens, while Class II antibodies target HLA-DR, -DQ, and -DP antigens, each with distinct locations and functions on immune cells.
Clinical Significance in Organ Compatibility
The presence of pre-formed HLA antibodies is a major factor determining the success or failure of an organ transplant procedure. If a recipient has HLA antibodies that match the donor’s specific HLA proteins, the immune system is already armed for a rapid attack. This immediate recognition can trigger hyperacute rejection, a destructive process that begins within minutes to hours of blood flow being established to the new organ. Hyperacute rejection involves the pre-formed antibodies binding to the blood vessel walls of the donor organ, initiating a complement cascade that causes immediate clotting and graft necrosis.
A patient with high levels of HLA antibodies against a broad range of the population is often referred to as a sensitized recipient. High sensitization makes it difficult to find a compatible donor, often measured by a high Panel Reactive Antibody (PRA) score. The most concerning antibodies are Donor-Specific Antibodies (DSAs), which target the specific HLA proteins of the intended organ donor, linking directly to higher rates of graft rejection and poorer survival outcomes.
Detecting HLA Antibodies
Assessing the risk posed by HLA antibodies requires specialized testing to determine both the level of overall sensitization and the specific targets of the antibodies. One initial screening test is the Panel Reactive Antibody (PRA) assay, which provides a numerical percentage representing the proportion of the general population to which the recipient would likely react. A high PRA score indicates a highly sensitized patient who will require a more extensive search for a compatible donor.
More specific testing is conducted using solid phase assays, such as bead-based technology, which uses microbeads coated with purified, single HLA proteins. This method allows clinicians to precisely identify which HLA types the recipient’s antibodies are targeting. This detailed information is used to guide donor selection and risk assessment before transplantation.
The final compatibility assessment is the crossmatch test, performed immediately before the transplant surgery, which mixes the recipient’s serum with the specific donor’s cells. A positive crossmatch indicates that the recipient has antibodies that immediately attack the donor cells, signaling a high risk of hyperacute rejection and typically leading to the cancellation of the transplant.