Being “HLA class 2 antibody positive” means you have immune proteins that can recognize and react against tissue markers from another person. Their presence is a consideration in medical procedures involving tissue from another individual, most notably organ transplantation. Understanding your HLA antibody status helps ensure the success of such procedures.
The Role of HLA in the Immune System
The body’s immune system distinguishes its own cells from foreign invaders like bacteria or viruses using markers called Human Leukocyte Antigens (HLAs). These proteins are on the surface of most cells and function like a cellular identification card. They signal to immune cells that they are part of “self” and should not be attacked, which is how the body protects itself from threats.
There are two main categories of HLA proteins. Class 1 HLAs are found on nearly every cell, presenting fragments of proteins from within the cell to the immune system. If a cell is infected with a virus, it will display viral fragments via its Class 1 HLA markers. This signals cytotoxic T-cells to destroy the infected cell as a defense against intracellular pathogens.
Class 2 HLAs are found only on specialized immune cells, like B-cells and antigen-presenting cells. These cells engulf materials from outside the cell, process them, and display fragments on their Class 2 HLA markers. This presentation activates T-helper cells, which coordinate a broader immune response. This includes stimulating B-cells to produce antibodies against that specific foreign substance.
Development of HLA Antibodies
Developing antibodies against HLA markers is a natural immune response to foreign human tissue. These antibodies are not the result of an illness but are created when the immune system encounters HLA proteins different from its own. This process, known as sensitization, primes the body to recognize and react to those specific foreign HLA types in the future.
A person can become sensitized and develop HLA antibodies in three main ways. The first is pregnancy, as a fetus inherits half of its HLA markers from the father, exposing the mother’s immune system to foreign antigens. Blood transfusions are another cause, as donor blood contains cells with different HLA markers. A previous organ or tissue transplant also introduces a large amount of foreign HLA-marked tissue, triggering the production of antibodies.
Implications for Organ Transplantation
For individuals needing an organ transplant, being positive for HLA class 2 antibodies presents a challenge. These pre-existing antibodies make the patient “sensitized,” meaning their immune system is prepared to attack tissues with specific HLA markers. If a donor organ has the same HLA class 2 proteins that the recipient has antibodies against, the immune system can attack the organ, leading to rejection.
Transplant centers quantify this risk using a Panel Reactive Antibody (PRA) test. The PRA test measures a patient’s blood serum against a panel of cells from diverse blood donors representing the general population. The result is a percentage estimating the likelihood of a positive reaction to a random donor. A high PRA score indicates antibodies against many HLA antigens, making it more difficult to find a compatible organ.
Before a transplant proceeds, a final compatibility test called a crossmatch is performed. This test mixes the patient’s serum with lymphocytes from the potential donor. If the patient’s antibodies bind to the donor’s cells, it results in a “positive crossmatch,” indicating a high risk of immediate rejection. A positive crossmatch for Class 2 antibodies involves the patient’s antibodies reacting with the donor’s B-cells, which prevents the transplant from moving forward with that donor.
Managing High HLA Antibody Levels
High levels of HLA antibodies, or a high PRA, complicate the search for a compatible organ but do not make transplantation impossible. Medical strategies can manage this challenge by either reducing the problematic antibodies or finding a way around the incompatibility.
One strategy is desensitization therapy, which aims to lower the number of circulating HLA antibodies in the bloodstream. This can make a transplant with a previously incompatible organ feasible. The therapy often involves plasmapheresis, a procedure that filters the blood to remove antibodies from the plasma. This is often paired with intravenous immunoglobulin (IVIG), which helps dilute and neutralize the patient’s HLA antibodies.
An alternative is participating in a paired donation program, common in kidney transplantation. These programs are organ-swapping systems where a patient with a willing but incompatible live donor can enter a registry with other incompatible pairs. Computer algorithms search for a way to exchange donors among the pairs so each recipient gets a compatible organ. This system expands the donor pool and creates opportunities for transplants that would otherwise be impossible.