What are the implications of proceeding with a kidney transplant from a donor with 10 eplet mismatches in the DPB1 locus, including 8V, 9Y, 9YL, 11L, 57D, 65L, 65LK, 76V, 84DEAV, and 96K?

DPB1 Eplet Mismatches in Kidney Transplantation

Proceeding with a kidney transplant from a donor with 10 eplet mismatches in the DPB1 locus is acceptable as DPB1 mismatches do not significantly impact overall survival, though they may increase the risk of graft-versus-host disease.

Understanding DPB1 Mismatches and Their Impact

Role of DPB1 in Transplantation

• DPB1 functions as a classical transplantation antigen, but its impact differs from primary HLA loci (A, B, C, DRB1) 1
• DPB1 typing may be performed if a permissive mismatching strategy is to be used, but it is not considered a primary matching criterion 2
• DPB1 is not in linkage disequilibrium with the remainder of the HLA genes, making mismatches common even in otherwise well-matched donor-recipient pairs 3

Clinical Impact of DPB1 Mismatches

• Mismatches at HLA-DP did not significantly affect overall mortality in large studies, unlike mismatches at HLA-A, B, C, or DRB1 2
• DPB1 mismatches are associated with increased risk of acute graft-versus-host disease (GVHD) 1, 3
• The increased risk of GVHD with DPB1 mismatches is often offset by a decreased risk of disease relapse, resulting in no net effect on survival 2

Permissive vs. Non-Permissive DPB1 Mismatches

T-Cell Epitope (TCE) Classification

• DPB1 mismatches can be classified as either permissive or non-permissive based on T-cell epitope groups 2, 3
• Non-permissive mismatches (occurring between different TCE groups) are associated with higher risks of acute GVHD compared to permissive mismatches 3
• Recent NMDP/CIBMTR guidelines confirmed the adverse impact of non-permissive HLA-DPB1 mismatches on outcomes 2

Eplet Mismatches

• Eplet mismatches represent specific epitope differences between donor and recipient HLA molecules 4, 5
• The number of eplet mismatches may be more important than the number of allele mismatches in predicting immunogenicity 5
• In kidney retransplantation, patients with fewer epitope mismatches showed better graft outcomes than those with more epitope mismatches, even when the number of allele mismatches was higher 5

Recommendations for This Case

Assessment of the 10 DPB1 Eplet Mismatches

• The specific eplet mismatches listed (8V, 9Y, 9YL, 11L, 57D, 65L, 65LK, 76V, 84DEAV, 96K) should be evaluated to determine if they are within or between TCE groups 2, 3
• The immunogenicity of these specific eplets should be considered, as some epitopes may be more immunogenic than others 5

Balancing Risks and Benefits

• For patients with early-stage or low-risk diseases, HLA matching has a greater effect on mortality compared to those with intermediate or advanced diseases 2
• The clinical status of the patient may affect the acceptable level of mismatching 2
• If the patient is sensitized with anti-HLA antibodies, additional testing for donor-specific antibodies against these DPB1 epitopes should be performed 2

Monitoring and Management

• Patients receiving transplants with DPB1 mismatches should be monitored closely for signs of GVHD 3, 1
• Appropriate immunosuppression strategies should be considered based on the epitope mismatch load 4

Conclusion

• While DPB1 matching is beneficial when possible, mismatches at this locus are common and generally acceptable 2
• The presence of 10 eplet mismatches in the DPB1 locus should not be a contraindication to proceeding with the kidney transplant if the donor is otherwise well-matched at the primary HLA loci (A, B, C, DRB1) 2
• Consider consulting with an HLA expert to determine if these specific eplet mismatches are permissive or non-permissive to better assess the immunological risk 2