Why are cheek swabs taken for tissue typing if Human Leukocyte Antigen (HLA) typing has already been done with blood?

Why Cheek Swabs Are Taken for Tissue Typing After Blood HLA Typing

Cheek swabs are collected for tissue typing even after blood HLA typing to provide redundancy, verify results, and ensure accuracy in the critical process of HLA matching for transplantation, as recommended by transplant guidelines. 1, 2

Reasons for Collecting Both Blood and Cheek Swab Samples

Verification and Quality Assurance

• Blood and cheek swab samples serve as independent verification methods, ensuring accuracy of HLA typing results
• Redundancy is crucial in transplantation where HLA matching directly impacts mortality and graft survival
• Guidelines recommend multiple sample types to minimize the risk of typing errors 2

Technical Advantages of Different Sample Types

1. DNA Quality and Quantity:

   • Cheek swabs provide high-quality genomic DNA that may complement blood samples
   • Different DNA sources can help overcome potential technical limitations in either sample

2. Sample Verification:

   • Using two different tissue sources confirms that results represent the patient's true HLA type
   • Prevents potential sample mix-ups or contamination issues 1

3. Backup Sample Source:

   • Provides an alternative source if blood sample DNA extraction fails or yields insufficient material
   • Particularly important in time-sensitive transplant situations 1

Clinical Importance of Accurate HLA Typing

Critical for Transplant Success

• Each additional HLA mismatch increases graft failure risk (HR 1.078 per mismatch) 2
• High-resolution HLA typing is essential for identifying compatible donor-recipient pairs 2
• Mistyping rates can be significant: 36.3% in African American patients and 8.5% in Caucasian patients using older methods 2

Modern Molecular HLA Typing Requirements

• Current guidelines recommend high-resolution (allele-level) typing for multiple HLA loci:
  • HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ (both DQA1 and DQB1) 2
• This comprehensive typing requires highly reliable DNA sources 1

Technical Considerations in HLA Typing

Evolution from Serological to Molecular Methods

• Traditional serological methods used blood lymphocytes but had significant limitations 3, 4
• Modern molecular methods (SSO, SSP, NGS) require high-quality DNA which can be obtained from either blood or cheek swabs 5

Resolution of Ambiguities

• High-resolution typing may encounter ambiguities requiring additional testing 6
• Having multiple DNA sources available allows for resolution of these ambiguities without recalling the patient

Best Practices in HLA Typing Laboratories

Quality Control Standards

• Tissue typing laboratories must follow strict guidelines for safety and reproducibility 7
• Multiple sample types support quality control processes required for national and international accreditation 7

Comprehensive Approach to Transplant Matching

• Modern transplant programs increasingly use eplet matching (analyzing small patches of surface-exposed amino acids) 2
• This sophisticated matching requires highly accurate HLA typing data, supporting the need for redundant sample collection

Common Pitfalls to Avoid

• Relying on a single sample source: Can lead to delays if sample quality issues arise
• Using outdated typing methods: Modern molecular methods require appropriate DNA sources
• Incomplete HLA typing: All relevant loci (including HLA-DQ) must be typed for optimal matching 2

In summary, collecting both blood and cheek swab samples represents best practice in HLA typing for transplantation, ensuring the highest possible accuracy in this critical process that directly impacts patient outcomes.