HLA-DP Matching Is Not Clinically Relevant in 10/10 HLA Matched Transplants: A Single Center Study

The association between HLA-DP and hematopoietic stem cell transplantation (HCT) outcomes is still questionable. In the present study, we examined 80 patients who underwent first allogeneic HCT between the years of 2005-2008 and were followed up for at least 2 years post transplant. These patients were 10/10 matched for HLA-A, -B, -C, -DR and –DQ at high resolution using Sequence Specific Priming (SSP) and/or Sequence Based Typing (SBT). We analyzed the impact of donor/recipient (D/R) mismatches at HLA-DPA1 and HLA-DPB1 on different HCT outcomes including aGVHD, cGVHD, and risk of disease relapse in a single center study. Additionally, we classified HLA-DPB1 mismatches as permissive or non-permissive according to a previously described TCE4 algorithm and attempted to confirm its efficacy. Each categorical testing variable were compared with the different clinical end points by 2-tailed Fischer’s exact test. The magnitude of effect was estimated by risk ratios and their 95% confidence intervals. “p” value ≤0.05 (two-sided) was considered significant. A total of 160 alleles were observed at HLA-DPA1 and 159 alleles were observed at HLA-DPB1 locus. HLA-DPA1 and DPB1 allelic frequencies in the study population were not significantly different from those previously observed in other Caucasian populations.  At DPA1 locus, D/R mismatching was observed in 15% of D/R pairs, however almost all of them were mismatched at the level of single allele. Since only one patient was mismatched for both DPA1 alleles, the effect of DPA1 mismatches were not analyzed for single or double mismatches.  At the DPB1 locus, 44% D/R pairs were found mismatched, including 24% for single allele and 20% for both alleles. No variables analyzed (allelic or non-permissive mismatches) were significantly associated with any transplant outcomes evaluated in this patient cohort.  Our study did not confirm the association between HLA-DP mismatches and HCT outcomes. The TCE4 algorithm also did not yield significant advantageous results. Our results are in accord with a recent French study but disconcordant with various studies conducted elsewhere, including the United States and the United Kingdom.  Further molecular study of HLA-DP in the clinical setting is warranted to further elucidate the role of this gene and its mismatching on HCT outcome.