Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation

Abstract

Key Points Mismatches in alleles C*03:03/C*03:04 were most frequent (68.7%) among the transplants with a single allele level mismatch in HLA-C. The 7/8 C*03:03/C*03:04 mismatch group was not significantly different from the 8/8 HLA matched transplants in any transplant outcome.

HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation

“…Thus, allele mismatches differ from antigen mismatches in the degree of sequence similarity 3,5 and in expression levels, and these features may contribute to the historically lower risks of allele compared with antigen mismatches. These results are consistent with recent studies demonstrating that the HLA-C*03:03/03:04 mismatch is a well-tolerated highfrequency mismatch 24,25 and provide a potential mechanism (ie, low expression) for why this particular mismatch is permissive.…”

“…6,7,24,25 Restriction of the study population to pairs with only 1 HLA-C mismatch removes any contribution of disparity at other HLA loci and addresses whether, among the spectrum of HLA-C mismatches, there are combinations of mismatches that are better tolerated than others.…”

How to select the best available related or unrelated donor of hematopoietic stem cells?

“…28 Furthermore, an initial observation that HLA-B and -C incompatibilities were better tolerated than -A or -DRB1 mismatches 11 has not been confirmed in more recent studies. 5,29 In their latest report Morishima et al 15 provided evidence that single HLA-A, -B or -C allele mismatches and double HLA-DRB1/DQB1 mismatches are associated with increased mortality in non-T-cell-depleted bone marrow transplantation. Interestingly single HLA-DRB1, -DQB1 or -DPB1 mismatches did not significantly affect overall survival rate.…”

“…18,20 However this could possibly be explained by the very high frequency (68.7%) of C*03:03/03:04 mismatches in the NMDP study. 29 This incompatibility had previously been reported to be more permissive, on the basis of in vitro assays measuring direct cytotoxic T-lymphocyte alloreactivity.…”

High-risk HLA alleles for severe acute graft- versus -host disease and mortality in unrelated donor bone marrow transplantation

“…The risk of transplant-related immunological events may vary according to patient-donor mismatching HLA locus, [1][2][3][4] mismatching specific HLA epitopes, 5,6 and specific mismatch combinations. 7 Furthermore, several studies have demonstrated that specific individual HLA genotypes may also affect transplant outcome, [8][9][10][11][12] although the results are not always consistent.…”