Ampath Chats

Tissue Typing: HLA Typing and Screening

Ampath Chats
Tissue Typing: HLA Typing and Screening
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PATHCHAT Edition No. 55
April 2019
Please contact your local Ampath pathologist for more information.

Author: Dr. Petri Swanepoel, MBChB (UP), MMed (Haem) (UP), FCPath (SA) (Haem)

Introduction

HLA Typing and Screening at Ampath

  • Ampath Immunology now offers HLA tissue typing and antibody screening using Luminex PCR-based multiplex technology.
  • This platform ensures accurate, reliable, and standardized results with a faster turnaround time.

📌 Human leukocyte antigen (HLA) testing is critical in transplantation, disease association studies, and immune response research.

Introduction to HLA Molecules

Major Histocompatibility Complex (MHC) Overview

  • HLA genes are located on the short arm of chromosome 6.
  • MHC encodes cell surface markers essential for immune system function.
  • HLA molecules present proteins (self or non-self) to T-lymphocytes, influencing immune responses.

🔹 HLA Class I and Class II Molecules:

Class I (Expressed on All Nucleated Cells & Platelets):

  • HLA-A
  • HLA-B
  • HLA-C

Class II (Expressed on Antigen-Presenting Cells):

  • HLA-DR
  • HLA-DQ
  • HLA-DP

📌 HLA genes are highly polymorphic, leading to extensive diversity in populations.

HLA Typing: Indications & Methods

Clinical Applications of HLA Typing:

  • Transplant Medicine:
    • Determines donor-recipient tissue compatibility.
    • Prevents solid organ rejection and graft-versus-host disease (GVHD) in stem cell transplants.
  • Disease Associations:
    • Helps diagnose conditions linked to specific HLA alleles.
  • Pharmacogenomics:
    • Identifies genetic markers for drug hypersensitivity reactions (e.g., HLA-B*57:01 and Abacavir hypersensitivity).
  • Immunotherapy & Vaccine Development:
    • Used in cancer immunotherapy and vaccine research.

Molecular vs. Serological HLA Typing:

Serological Typing (Older Method, Limited Use):

  • Uses antisera to detect specific HLA molecules.
  • Low reproducibility and limited detection of rare antigens.

Molecular Typing (Current Standard, High Accuracy):

  • Uses PCR-based or DNA sequencing methods.
  • Higher resolution and specificity.
  • Better reproducibility and ability to detect rare alleles.

📌 Molecular HLA typing has replaced serological methods for improved accuracy and reliability.

HLA Nomenclature & Sample Collection

HLA Naming System:

  • More than 21,000 known HLA alleles.
  • New alleles are assigned by the World Health Organization’s Nomenclature Committee for the HLA System.
  • Full details available at: hla.alleles.org

Sample Collection for HLA Typing:

  • Collect 4 EDTA (purple top) or ACD (light yellow top) tubes.
  • Samples accepted Monday to Friday.

📌 HLA testing requires high-quality DNA; ensure correct sample collection for accurate results.

HLA Antibody Screening

Why Screen for HLA Antibodies?

  • HLA antibodies can cause graft rejection in organ and stem cell transplantation.
  • Donor-specific antibodies (DSA) are associated with poor graft survival.
  • Identifying DSAs allows better immunological risk stratification and post-transplant monitoring.

Luminex Technology – LabScreen Testing at Ampath

  • Step 1: Screening test detects the presence of HLA Class I or Class II antibodies.
  • Step 2: If positive, a detailed assay specifies the antibody at the allelic level.

📌 HLA antibody screening improves transplant success and long-term graft survival.

Post-Transplant Antibody Monitoring

Importance of Post-Transplant Monitoring:

  • Detects low-level or newly formed DSAs.
  • DSAs may indicate early signs of chronic graft rejection before biochemical markers (e.g., creatinine in kidney transplants).

Sample Collection for Post-Transplant Monitoring:

  • Collect 1 SST tube (yellow top).
  • Samples accepted Monday to Friday.

📌 Post-transplant antibody monitoring helps predict graft rejection and allows timely interventions.

HLA & Disease Associations

HLA Typing in Autoimmune & Genetic Disorders:

  • HLA-B*27 → Ankylosing spondylitis.
  • **HLA-DRB103/04 → Type 1 diabetes mellitus.
  • **HLA-DQ02/08 → Coeliac disease.

HLA Typing in Drug Reactions:

  • HLA-B*57:01 → Hypersensitivity to Abacavir (HIV treatment).

📌 HLA typing assists in diagnosing immune-mediated diseases and preventing severe drug reactions.

Contact Information for HLA Testing at Ampath

For HLA Typing & Screening Queries:

  • Ampath’s Cellular Immunology Laboratory: 012 678 0530
  • Dr. Petri Swanepoel: 012 678 0613/4

📌 For more information on HLA testing, consult Ampath’s Immunology Department.

Key Takeaways for Clinicians

HLA typing plays a critical role in transplant medicine, disease diagnosis, and pharmacogenomics.
Molecular HLA typing using PCR-based methods is more accurate than serological methods.
HLA antibody screening identifies donor-specific antibodies, improving transplant outcomes.
Post-transplant antibody monitoring can predict graft rejection before clinical deterioration.
HLA associations aid in diagnosing autoimmune diseases and identifying drug hypersensitivity risks.

📌 HLA typing and antibody screening are essential tools for precision medicine and transplant success.