Resolution-Aware Eight-Locus HLA Diversity Profiling and Rare Allele Interpretation in an Eastern Chinese Transplant-Typing Cohort.

HLA diversity profiling is essential for transplant-typing practice, yet its interpretation is complicated by heterogeneous typing resolution and ambiguity in routine clinical datasets. We analysed eight-locus HLA genotyping results from 1388 individuals in an Eastern Chinese transplant-typing cohort (2021-2026) using a resolution-aware two-stage analytical framework-an approach that explicitly distinguishes first-field (allele-group) summaries from strict two-field allele-level analysis. HLA diversity profiling is defined as the systematic characterisation of allele/allele-group frequency distributions, heterozygosity and diversity metrics (Shannon entropy, evenness). Stage 1 summarised assay-derived first-field (allele-group) codes with complete coverage across all loci (2776 allele copies per locus), whereas Stage 2 evaluated strict two-field alleles restricted to loci achieving a > 45% two-field resolution threshold. Observed heterozygosity varied markedly across loci, ranging from 0.484 at HLA-DPA1 to 0.923 at HLA-B. At Stage 1, 43 rare allele-group codes (< 1%) were identified, disproportionately contributed by HLA-DPB1 (51.2%), consistent with resolution- and ambiguity-related inflation of apparent rare categories. At Stage 2, 68 rare two-field alleles (< 1% within locus-specific resolvable subsets) were identified; all were officially assigned and listed in the IPD-IMGT/HLA Database and documented in the Allele Frequency Net Database, with 97.1% having reported Chinese population records. Classification using the Common, Intermediate and Well-Documented (CIWD) catalogue showed that most cohort-defined 'rare' alleles were not globally rare. Together, these findings demonstrate that apparent rare allele burden in transplant-typing cohorts is strongly influenced by typing resolution and ambiguity handling. The resolution-aware framework presented here provides a transparent template for HLA diversity reporting and rare allele interpretation in heterogeneous clinical transplant-typing datasets.