HLA-A alleles influencing NK cell function impact AML relapse following allogeneic hematopoietic cell transplantation Journal Article
| Authors: | van der Ploeg, K.; Le Luduec, J. B.; Stevenson, P. A.; Park, S.; Gooley, T. A.; Petersdorf, E. W.; Shaffer, B. C.; Hsu, K. C. |
| Article Title: | HLA-A alleles influencing NK cell function impact AML relapse following allogeneic hematopoietic cell transplantation |
| Abstract: | HLA-B allotypes exhibiting the Bw4 epitope trigger variable inhibitory signaling of KIR3DL1 receptor types, where strong inhibitory HLA-B and KIR3DL1 allele combinations are associated with increased risk for relapse of acute myelogenous leukemia (AML) following allogeneic hematopoietic cell transplantation (HCT). Several HLA-A allotypes also exhibit the Bw4 epitope. Studies with natural killer (NK) cell clones have demonstrated NK inhibition via KIR3DL1 by HLA-A Bw41 allotypes, but did not delineate strengths of inhibition or hierarchies of NK education. Using primary NK cells from healthy donors, we demonstrate that HLA-A*23, HLA-A*24, and HLA-A*32 proteins are expressed at different densities and exhibit different capacities to educate and inhibit KIR3DL1-expressing NK cells in vitro. Among the HLA-A Bw41 allotypes, HLA-A*24 and HLA-A*32 demonstrate the strongest inhibitory capacity. To determine if HLA-A allotypes with strong inhibitory capacity have similar negative impact in allogeneic HCT as HLA-B Bw41 allotypes, we performed a retrospective analysis of 1729 patients with AML who received an allogeneic HCT from a 9/10 or 10/10 HLA allele-matched unrelated donor. Examination of the donor-recipient pairs whose Bw4 epitope was exclusively contributed from HLA-A*24 and A*32 allotypes revealed that patients with HLA-A*24 who received an allograft from a KIR3DL11 donor experienced a higher risk of disease relapse (hazard ratio, 1.65; 95% confidence interval, 1.17-2.32; P 5.004) when compared with patients without a Bw4 epitope. These findings indicate that despite weak affinity interactions with KIR3DL1, common HLA-A allotypes with the Bw4 epitope can interact with KIR3DL11 donor NK cells with clinically meaningful impact and provide additional insight to donor NK alloreactivity in HLA-matched HCT. © 2020 by The American Society of Hematology |
| Keywords: | adult; controlled study; protein expression; unclassified drug; human cell; major clinical study; allele; cell function; protein interaction; in vitro study; retrospective study; prediction; high risk patient; allogeneic hematopoietic stem cell transplantation; natural killer cell; cell density; hla a antigen; hla b antigen; donor selection; leukemia relapse; alloimmunity; acute myeloid leukemia; killer cell immunoglobulin like receptor 3dl1; immunogenetics; hla a24 antigen; human; priority journal; article; allotype; antigen hla a23; antigen hla a32 |
| Journal Title: | Blood Advances |
| Volume: | 4 |
| Issue: | 19 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2020-10-13 |
| Start Page: | 4955 |
| End Page: | 4964 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2020002086 |
| PUBMED: | 33049053 |
| PROVIDER: | scopus |
| PMCID: | PMC7556125 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
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