- Doing things right
- Finding the best donor
- Providing information that can make a difference
- Developing new methods
The primary goal of the histocompatibility laboratory is to provide the best care to the patients that use our services. Guidelines and standards help us accomplish that goal. Standards are rules of operation prescribed by the government and the accrediting agencies.
The Federal Government, acting through the Health Care Financing Administration (HCFA) and the Department of Health and Human Services (HHS) has issued rules for all laboratories that "examine human specimens for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings" in the Clinical Laboratory Improvement Amendments of 1988 (CLIA). These rules and regulations cover test management, quality control, quality assurance, proficiency testing, personnel, accreditation, and inspection. They include special requirements for histocompatibility laboratories.
American Society for Histocompatibility and Immunogenetics (ASHI)
One of the major objectives of ASHI is "to maintain the highest standards of reliability and quality in histocompatibility testing laboratories." In order to achieve this objective, ASHI has established standards that all histocompatibility laboratories must meet if their services are to be considered acceptable. These standards cover a wide range of issues such as: personnel qualifications, quality assurance, typing for HLA antigens by serology, or cellular or molecular-based methods, antibody screening to determine patient sensitization, flow cytometry, etc. ASHI performs an on-site laboratory inspection every two years to ensure that accredited laboratories comply with all the standards. In 1994, ASHI was awarded deemed status as an approved agency for HCFA, meaning that ASHI inspected laboratories would be CLIA certified.
United Network for Organ Sharing (UNOS) and National Marrow Donor Program (NMDP)
Both UNOS and NMDP utilize the accreditation services of ASHI to inspect and certify that member histocompatibility laboratories comply with the standards.
Some histocompatibility laboratories may also be accredited by other agencies such as the College of American Pathologists (CAP), or the American Association of Blood Banks (AABB).
Tissue Typing Laboratories serve centers that do many different types of transplants including kidney, heart, lung, liver, pancreas, small intestine and bone marrow. Each type of transplants has its own requirements.
Red cell ABO antigens and the HLA antigens, are important in kidney transplantation. Matching for the ABO blood group is essential, as a mismatch would lead to immediate failure. HLA matching is important but not essential. HLA well-matched kidney transplants do much better than those that are mismatched. Patients in need of a kidney transplant are typed for ABO and HLA and the information is listed with the UNOS computers. In addition, tests are performed to monitor the development of antibodies against HLA antigens. Such immune system proteins might attack a transplanted kidney and cause rejection. Potential donors are also typed for ABO and HLA antigens and the UNOS computer identifies the best possible recipient. When a donor kidney is found to be a perfect match for a patient anywhere in the country, the kidney is offered to that patient. Luckily, kidneys can tolerate being outside the body for up to two or three days and thus they can be sent to perfectly matched recipients. Before the transplant surgery, a crossmatch is performed in the histocompatibility laboratory, to verify that the recipient does not have antibodies that might attack the donor kidney.
Some patients have family members who are willing to donate one of their kidneys. In this case, the patient and potential donor are typed for ABO and HLA antigens and a crossmatch is performed. The crossmatch is repeated immediately before the transplant to be absolutely sure that the donor and the recipient are compatible.
Transplantation of Other Solid Organs
The ABO blood group, the physical size of the donor and recipient, and the seriousness of the recipient's illness are more important than HLA antigens in deciding who is best suited to receive a heart, liver or other organ. While a good match does improve the long-term survival of hearts, these organs can only tolerate being out of the body for twelve hours or less and that is not enough time for HLA typing and sharing to occur. Crossmatches between donor and recipients are performed but even these are often done after the surgery has started. The results may help the physicians choose the best drugs to block the recipient's immune system to prevent rejection.
Bone Marrow Transplantation
Histocompatibility laboratories play an important role in bone marrow transplantation. This is because a well matched donor is crucial to the success of the transplant. When a patient is evaluated for a bone marrow transplant, the histocompatibility laboratory types their HLA antigens and also those of as many family members as possible (parents, brothers and sisters). Because of the way the HLA antigens are passed on from parents to children, the most likely person to be a perfect match will be a brother or sister. The parents are usually only a half match. If a donor is not found in the immediate family, sometimes another relative, like an uncle, aunt, cousin, child or grandparent might be a good match.
If there are no family members that are HLA matched, the next option is to search for a donor in the NMDP registry. This is a computer database of the HLA types of over two million volunteer donors. The best-matched donor is contacted, asked to give blood to confirm the match, and then asked to donate bone marrow to provide a new blood and immune system for the patient. Unlike solid organ transplants, the ABO blood antigens are not used to choose a bone marrow donor. However, HLA antigen matching is more strict, because the success of this procedure and the well being of the patient depend on it.
Histocompatibility laboratories work closely with the members of the transplant team and also with other physicians to help them make decisions on how best to treat their patients.
For solid organ transplant patients, the laboratory monitors the development of anti-HLA antibodies. These tests can determine if a particular organ is compatible and can provide information about what percentage of donated organs might be compatible and how long a person might have to wait for one.
For bone marrow transplant patients, the laboratory can look at the family typings and help the physician decide which extended family members might be eligible to become donors. They also can assist in the search of the donor registries.
The laboratory can help the physician decide which patients need to be treated more aggressively with drugs to block the immune system to prevent rejection. For solid organ transplant patients, a laboratory can save frozen cells from the donor and use them to perform crossmatch tests to see if antibodies against the transplant are being formed, a probable indication of rejection. The laboratory can also look for donor cells in the patient's blood, as an indication of development of tolerance of the donor organ. This type of test is also performed for bone marrow transplant patients to see if the transplant was successful and donor-type cells are now found in the circulation.
Many histocompatibility laboratories are actively engaged in research and development. There are many ongoing studies: to find more accurate and efficient ways to type for the HLA antigens; to identify new HLA antigens; to recognize which HLA antigens are most important when matching for organ and bone marrow transplants; to find the best way to prove that donor and recipient are compatible; and to find which HLA antigens are associated with diseases. Some laboratories study the HLA antigens of indigenous populations, as a way of tracing ancestry and history. And also, as a way to better type for the antigens prevalent in minority populations. Other laboratories study ways to monitor patients after transplantation to ensure that they keep their transplanted organ as long as possible. By learning more about HLA antigens and histocompatibility, we are constantly working to improve the care we give to our patients.
Continuing education programs are very important for technologists and laboratory directors to learn about advances being made. ASHI sponsors Regional Workshops and an Annual Meeting as a means of enhancing the dissemination of information in our field. Other societies also hold scientific meetings and workshops that are of interest to histocompatibility specialists.
Contributed by Amy B. Hahn, Ph.D.