Histocompatibility (HLA) laboratory

A histocompatibility laboratory (also called an HLA laboratory or immunogenetics laboratory) is a specialized clinical laboratory that performs human leukocyte antigen (HLA) typing, HLA-antibody screening and identification, and crossmatching to assess immunologic compatibility between organ and tissue donors and recipients.[1][2] Its results determine which transplant candidates may safely receive a given donor organ and feed directly into the national allocation system, making the HLA laboratory an indispensable partner of transplant centers, organ procurement organizations, and stem-cell donor registries.[2][3] Histocompatibility testing is the laboratory basis of transplant immunology.

Functions

Histocompatibility laboratories perform several distinct but related tests:[1][2]

• HLA typing. The laboratory determines a donor's and candidate's HLA alleles across class I (HLA-A, -B, -C) and class II (HLA-DR, -DQ, -DP) loci. Modern typing is performed by molecular methods, polymerase chain reaction with sequence-specific oligonucleotide probes or primers, and increasingly next-generation sequencing (NGS), which have largely replaced older serologic (antibody-based) typing.[1][2] Comprehensive and accurate HLA typing within a short turnaround time is critical for deceased-donor allocation, because erroneous typing can cause recipient death, graft failure, or organ wastage.[3]
• HLA-antibody screening and identification. The laboratory detects and characterizes a candidate's anti-HLA antibodies, most often using solid-phase single-antigen bead assays read on a Luminex platform. From the antibody profile it derives the panel-reactive antibody (PRA) and calculated PRA (cPRA), a measure of how sensitized a candidate is and how difficult it will be to find a compatible donor.[1][2]
• Crossmatching. A crossmatch tests whether a candidate's serum contains antibodies that react against a specific donor's cells. Physical crossmatches include the complement-dependent cytotoxicity (CDC) crossmatch and the more sensitive flow-cytometric crossmatch.[1][4] A virtual crossmatch (VXM) compares the candidate's identified unacceptable antigens against the donor's HLA type without a wet-lab cell test, and over the past decade has become the principal pre-transplant compatibility assessment in U.S. deceased-donor kidney transplantation.[5]
• Other roles. HLA laboratories also support hematopoietic stem-cell donor matching, platelet-refractoriness and transfusion support, disease-association testing (for example HLA-B27 or HLA-B*57:01 pharmacogenetic testing), and post-transplant antibody monitoring.[1][2]

Role in deceased-donor allocation

Because the HLA antigens used in matching are programmed into the OPTN computer system, the laboratory's typing and antibody results drive the deceased-donor match run: a candidate's "unacceptable antigens," entered by the laboratory, cause the system to bypass donors against whom the candidate is sensitized, effecting a virtual crossmatch at the point of allocation.[3][5] The virtual crossmatch lets organs be offered and accepted before a physical crossmatch is completed, which transplant professionals and HLA directors report can reduce cold-ischemia time, lower cost, and improve allocation efficiency, particularly under broader organ-sharing policies.[5] To guard against typing error, OPTN policy requires histocompatibility laboratories to perform confirmatory HLA typing for every deceased donor, two HLA typings from samples drawn at two separate times.[3]

Regulation and accreditation

HLA testing for transplantation is classified as high-complexity testing under the Clinical Laboratory Improvement Amendments (CLIA), so HLA laboratories must hold CLIA certification and meet CLIA personnel and quality standards.[2][6] In addition, the laboratory is typically accredited by the American Society for Histocompatibility and Immunogenetics (ASHI), an international professional society that accredits HLA laboratories to maintain quality standards for donor-recipient histocompatibility testing; UNOS/OPTN and the National Marrow Donor Program rely on ASHI (and equivalent) accreditation in their oversight of HLA laboratories, including review of critical typing errors.[6][7] The College of American Pathologists (CAP) offers an alternative recognized accreditation program for histocompatibility laboratories.[2]

Professional certification of HLA-laboratory personnel and directors is administered by the American College of Histocompatibility and Immunogenetics (ACHI). ACHI was formed in 2020 by combining the former American Board of Histocompatibility and Immunogenetics (ABHI), which operated through October 2020, with ASHI's Director Training, Review and Credentialing function; ABHI-era credentials (for example "CHT (ABHI)") were carried over as ACHI credentials.[8][9] ACHI develops and administers credentialing examinations for non-doctoral technologists, Certified Histocompatibility Associate (CHA), Certified Histocompatibility Technologist (CHT), and Certified Histocompatibility Specialist (CHS), and for doctoral directors at the Associate and Fellow levels; ASHI-approved directors and ABHI diplomates recognized before October 31, 2020 were automatically recognized as Fellows of ACHI.[8][9] The legacy doctoral diplomate credential is denoted D(ABHI).[9]

Personnel and director qualifications

A histocompatibility laboratory is led by a qualified laboratory director who holds CLIA director eligibility and, by convention, ACHI/ASHI director recognition (the D(ABHI) diplomate or ACHI Fellow grade), and who sets testing policy and signs out results.[2][8] Bench testing is performed by certified histocompatibility technologists (CHT/CHS), often also credentialed as medical laboratory scientists, working under a technical supervisor and the director.[2][8]

Quality

HLA laboratories operate under CLIA quality requirements, ASHI (or CAP) accreditation standards, and OPTN policy, with proficiency testing, competency assessment, and documented standard operating procedures.[2][6] Because a single typing or antibody-assignment error can produce a positive crossmatch missed at allocation, with potentially fatal consequences, laboratories use redundant typing methods and confirmatory testing as patient-safety controls, and accrediting bodies treat critical HLA typing errors as reportable events.[3][7]

See also

• Transplant immunology
• Transplant center / hospital
• The donation pathway

References

• Human Leukocyte Antigen (HLA) and transplant immunology. StatPearls. NBK538218. https://www.ncbi.nlm.nih.gov/books/NBK538218/
• American Society for Histocompatibility and Immunogenetics. About histocompatibility laboratories and accreditation. https://www.ashi-hla.org/
• Organ Procurement and Transplantation Network. Require Human Leukocyte Antigen (HLA) Confirmatory Typing for Deceased Donors. https://optn.transplant.hrsa.gov/policies-bylaws/public-comment/require-human-leukocyte-antigen-hla-confirmatory-typing-for-deceased-donors/
• The crossmatch in transplantation (CDC, flow, and virtual crossmatch). PMC10727546. https://pmc.ncbi.nlm.nih.gov/articles/PMC10727546/
• Virtual Crossmatch for Deceased Donor Kidney Transplantation in the United States: A Survey of Histocompatibility Lab Directors and Transplant Surgeons. PMC9991979. https://pmc.ncbi.nlm.nih.gov/articles/PMC9991979/
• American Society for Histocompatibility and Immunogenetics. Accreditation program. https://www.ashi-hla.org/page/Accreditation
• Organ Procurement and Transplantation Network. Histocompatibility policy and oversight of critical HLA typing errors. https://optn.transplant.hrsa.gov/policies-bylaws/public-comment/histocompatibility-hla-table-update-2025/
• American College of Histocompatibility and Immunogenetics. Certification (CHA, CHT, CHS; director grades). https://www.achicertification.org/
• American Society for Histocompatibility and Immunogenetics. FAQs for the ACHI (formation from ABHI + ASHI DTRC, 2020). https://cdn.ymaws.com/www.ashi-hla.org/resource/resmgr/docs/education/faqs_-_achi.pdf