Cheek Swab in Kidney Transplantation: HLA Typing for Donor-Recipient Matching
A cheek swab is required for kidney transplant recipients to obtain DNA for high-resolution HLA typing, which is essential for determining donor-recipient compatibility and minimizing rejection risk. 1, 2
Purpose of HLA Typing in Kidney Transplantation
HLA (Human Leukocyte Antigen) typing is a critical component of the transplantation process that serves several key functions:
- Donor-recipient matching: Identifies compatible donor-recipient pairs to minimize rejection risk
- Crossmatch testing: Determines whether recipients have preformed antibodies against donor HLA antigens
- Post-transplant monitoring: Helps identify donor-specific antibodies that may develop after transplantation
Why a Cheek Swab?
A cheek swab (buccal swab) provides a non-invasive method to collect epithelial cells containing DNA for molecular HLA typing. This approach offers several advantages:
- Non-invasive collection: Painless and requires no medical procedure
- High-quality DNA: Sufficient for modern molecular typing techniques
- Convenience: Can be performed in any setting without specialized equipment
Modern HLA Typing Techniques
Current guidelines strongly recommend molecular genotyping techniques over traditional serological methods 1:
- High-resolution 2-field HLA typing: Provides allele-level information rather than just antigen-level data
- Next-generation sequencing (NGS): Offers the most comprehensive and accurate HLA typing
The Kidney International guidelines specifically recommend performing allele-level genotyping of both donor and recipient for multiple HLA loci, including:
- HLA-A, HLA-B, HLA-C
- HLA-DR
- HLA-DQ (both DQA1 and DQB1) 2
Clinical Importance of High-Resolution HLA Typing
Improved Matching Accuracy
Traditional serological typing methods have significant limitations:
- Mistyping rates: 36.3% of African Americans showed either HLA-A or HLA-B discrepancies when comparing serological and molecular typing 1
- Only 8.5% of Caucasian kidney donors and recipients were mistyped using serological methods 1
Better Prediction of Transplant Outcomes
High-resolution typing provides several clinical benefits:
- Identifies previously unrecognized mismatches: Studies show additional mismatches in 64.1% of cases when using two-field (high-resolution) HLA typing compared to one-field (low-resolution) typing 3
- Improves graft survival: Each additional HLA mismatch increases risk of graft failure (HR 1.078 per mismatch) 4
- Reduces rejection risk: Lower eplet mismatch loads correlate with improved long-term outcomes 2
Special Focus on HLA-DQ
Recent evidence highlights the importance of HLA-DQ typing:
- DQ matching: Both DQα1 and DQβ1 chains contribute to antibody specificity 1
- Rejection risk: Each additional DQ eplet mismatch increases odds of antibody-mediated rejection 2
- Transplant allocation: Some systems now allocate 100 points for full DQ matching 2
Clinical Pitfalls to Avoid
- Incomplete HLA typing: Failing to type all relevant loci (especially HLA-DQ) can lead to unexpected rejection
- Relying on serological typing alone: Particularly problematic for African American patients who have higher mistyping rates 1
- Ignoring previous transplant history: Critical not to re-expose recipients to HLA class II antigens from previously rejected allografts 1
- Overlooking eplet matching: Modern approaches focus on eplet (small patches of amino acids) rather than just antigen matching 2
Alternative Methods When Donor DNA is Unavailable
In cases where donor DNA is unavailable (approximately 20% of post-transplant HLA-antibody assessments), alternative approaches include:
- Urine sampling: Donor renal tubular cells can be cultured from recipient urine as a source of donor DNA 5, 6
- Retrospective typing: All known mismatches can be detected from recipient urine samples with high accuracy 6
Conclusion
The cheek swab represents a simple but crucial step in the kidney transplantation process, providing DNA for high-resolution HLA typing that significantly impacts transplant outcomes. Modern molecular typing techniques have largely replaced traditional serological methods due to their superior accuracy and ability to identify previously unrecognized mismatches.