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ABO glycosyltransferases as potential source of minor histocompatibility antigens in allogeneic peripheral blood progenitor cell transplantation
Author(s) -
EizVesper Britta,
Seltsam Axel,
Blasczyk Rainer
Publication year - 2005
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2005.04370.x
Subject(s) - abo blood group system , glycosyltransferase , biology , genotype , transplantation , immunology , allele , phenotype , human leukocyte antigen , antigen , major histocompatibility complex , genetics , gene , medicine
BACKGROUND: Most studies indicate that the incidence of graft‐versus‐host disease (GVHD) is not increased in ABO‐mismatched allogeneic peripheral blood progenitor cell transplantation. These studies exclusively looked at ABO phenotypes without considering the fact that different genotypes hide behind identical phenotypes that encode for different sets of glycosyltransferases, thus providing a source for minor histocompatibility antigens (mHags). STUDY DESIGN AND METHODS: Therefore, whether peptides derived from ABO glycosyltransferases are capable of stimulating peptide‐specific T cells was investigated. T‐cell responses were identified by measuring intracellular interleukin‐2 expression. RESULTS: Individuals with ABO genotypes encoding glycosyltransferases lacking the peptide sequences used for stimulation showed T‐cell responses, whereas those expressing glycosyltransferases containing the respective peptide sequences proved to be tolerant, indicating that ABO peptides are allogeneic and may act as mHags. Interestingly, even ABO * O individuals were tolerant to O glycosyltransferase–derived peptides, which strongly suggests that truncated O transferases are expressed. CONCLUSION: Considering allelic ABO sequences, at least 15 percent of all phenotypically ABO‐matched transplant pairs can be expected to have genotype constellations relevant to GVHD. Therefore, the genotype behind the ABO blood group phenotype should be considered to answer the question of whether ABO mismatch is a risk factor of GVHD.