Publication Date:
2013-11-15
Description:
Minor histocompatibility antigens (mHA) mediate immune responses that can cause both graft vs. host disease (GvHD) and the graft vs. leukemia (GvL) effect observed in allogeneic stem cell transplantation (SCT). These responses result from donor T-cells being exposed to non-self peptides that are presented by HLA molecules on recipient cells. In contrast, cancer testis antigens (CTA) are peptide antigens derived from proteins, normally expressed only in male germ cells, but also aberrantly expressed in some tumors. These antigens can induce T-cell responses in an autologous setting without using T-cells from an allogeneic donor. Because, mHA that are expressed by hematopoietic tissue or leukemia could be therapeutic targets, which would enhance GVL without increasing the risk of GVHD we performed a genomics based mHA screen to identify high-value mHA. However, one of our predicted antigens, UNC-GRK4-1, was only expressed in testis and human AML, and has properties more consistent with a CTA. We used the Illumina NS-12 microarray platform to genotype 99 HLA-A0201 expressing myeloid leukemia patients and their HLA-matched donors at 13,917 non-synonymous coding single nucleotide polymorphisms (cSNPs). For both alleles in each of the 13,917 cSNPs we identified genetically predicted donor-recipient mHA responses, which were defined as the donor being homozygous for 1 allele and the recipient being either heterozygous or homozygous for the alternate allele. Using Fisher's exact test for each allele, we tested for the association between genetically predicted mHA responses and the clinical outcomes of remission vs. relapse over all 99 patients. Using the BioGPS database, we determined the tissue expression for the 261 alleles associated with remission to a p-value of
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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