*Purpose: Eplet matching is being promoted as a rational approach to prevent immune-mediated injuries in transplantation. We studied the frequencies of eplets in a Canadian population to inform strategies to secure HLA compatible transplants regionally and nationally.

*Methods: We analyzed data from the first phase of the Canadian Longitudinal Study on Aging (CLSA). A total of 6298 participants were of diverse ancestry from Alberta (N=613), British Columbia (N=1348), Manitoba (N=646), Newfoundland (N=493), Nova Scotia (N=665), Ontario (N=1357) and Quebec (N=1176)). All these participants had complete allele-level genotypes for 11-loci (HLA-A, -B, -C, -DRB1/3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1) imputed by the HLA*IMP:02 method. HLA genotypes were converted to epitypes using the eplet repertoire recorded on the HLA Epitope Registry (accessed September 2018). Frequencies of antibody-verified (AbVer) and non-AbVer eplets were determined. Intraclass Correlation Coefficients (ICC) were calculated to assess differences in eplet frequencies by participants’ province.

*Results: A total of 223 class I (72 AbVer) and 286 class II (82 AbVer) were observed in the cohort. Five eplets (0.01%) were not observed in any participant. There was significant agreement in eplet frequencies across Canadian provinces (ICC of 0.99). The eplets were distributed in the studied population as follows: 6 class I (0 AbVer) and 5 class II (0 AbVer) eplets were observed in <1%; 51 class I (22 AbVer) and 42 class II (11 AbVer) eplets were observed in 1-25%; 50 class I (22 AbVer) and 71 class II (25 AbVer) were observed in 25-50%; 45 class I (14 AbVer) and 59 class II (30 AbVer) were observed in 50-75%; and of 68 class I (14 AbVer) and 107 class II (16 AbVer) were observed in >75%.

*Conclusions: Similar eplet frequencies were observed across Canadian provinces. Thus, a strategy of matching at the eplet level to prevent immune-mediated injuries is expected to perform similarly across Canada. The understanding of risk associated with particular mismatched eplets, coupled with measured frequencies, can guide when regional allocation may need to be supplemented by national organ sharing policies.

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