Aim: In January 2025, the International ImmunoGenetics Information System (IMGT) reclassified the allele C04:09 from null (C04:09N) to low expression (C04:09L). This reclassification has important clinical implications for transplantation. Donor-recipient pairs previously considered matched due to the null designation may now be at risk for mismatch or the development of donor-specific antibodies (DSA) to C04:09L. To evaluate potential clinical impacts, we conducted a retrospective review of cases previously reported as C*04:09N within our patient population.
Methods: We reviewed all HLA typings performed from 2011 to the present. Typing methods included CareDx Olerup SSP (Sequence-Specific Primer), OneLambda SeCore™ Sanger Sequencing with Ambisov primers, OneLambda LABType™ SSO (Sequence-Specific Oligonucleotide), and Next Generation Sequencing (NGS) using either Omixon Holotype HLA 96/11 or GenDx NGSgo®-MX11-3. SSO was the primary method used for solid organ cases until transitioning to NGS, limiting our ability to resolve C04:01/C04:09N alleles due to a point deletion in exon seven. In contrast, methods used for stem cell cases fully resolved the ambiguity in accordance with National Marrow Donor Program (NMDP) requirements. HLA antibody testing was conducted with LABScreen™ Single Antigen Bead kits, which include one C04 bead (C04:01).
Results: We identified 24 cases of HLA-C04:09N. Review of 4 solid organ recipients and 8 stem cell recipients revealed no Cw4 antibodies. Three organ donors were transplanted into recipients not typed for Cw4; none developed Cw4 antibodies pre- or post-transplant. Two additional organ donors have not yet proceeded to transplant. Six NMDP stem cell donors were typed as C04:09N, with one proceeding to transplant with a matched recipient.
Conclusion: Our review found no clinical impact related to the reclassification of C04:09N to C04:09L in our patient population. No new mismatches were identified among stem cell recipients, and no de novo Cw4 antibodies were detected in organ recipients transplanted with C04:09L mismatches. Laboratory reporting processes have been updated to reflect the allele’s new status. Moving forward, primary NGS testing will standardize the identification of C04:09L for both stem cell and organ transplantation cases.
