Minor histocompatibility antigens as determinants for graft‐versus‐host disease after allogeneic haematopoietic stem cell transplantation

Abstract

Minor histocompatibility antigens (minor H antigens) are genetically polymorphic peptides that have been shown to elicit immune response when mismatched between donor and recipient of haematopoietic stem cell transplantation (HSCT). Depending on the expression profiles, mismatches in these genes may either lead to harmful graft-versus-host (GvH) reaction or desired graft-versus-leukaemia (GvL) effect. We analysed retrospectively the effect of HLA-restricted matching 11 established autosomal minor H antigens on the risk of graft-versus-host disease and relapse in 311 HLA-matched sibling HSCT of a single centre. Increased incidence of chronic GvH disease was shown to be associated with mismatches in the HA-8 and ACC-1. The mRNA expression profiles in a large set of healthy and malignant tissue samples of minor H antigen genes demonstrated in silico that the expression profiles of HA-8 and ACC-1 were surprisingly different: HA-8 gene was expressed in practically all tissues, whereas ACC-1 gene had a restricted profile. The results demonstrated that mismatches in minor H antigens HA-8 and ACC-1 predisposed to chronic graft-versus-host disease (GvHD).

Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation

“…31,32 The immunogenic potential of MICA polymorphisms has been also demonstrated in solid organ transplantation, in which processing of MICA antigens in host antigen-presenting cells may lead to alloantibodies, causing graft rejection. 9 This dual mechanism (CD94/NKG2D signaling and direct immunological recognition of MICA allotypes) may explain the findings in our study, as we found a tendency for higher relapse rates as a result of impaired relapse control in the 9/10 HLA-matched group and for higher NRM in the 10/10 HLA-matched group if MICA-129 were mismatched.…”

A divergent Pumilio repeat protein family for pre-rRNA processing and mRNA localization

“…It is overexpressed in breast cancer cells, with higher levels in more advanced stages (16). A peptide derived from human Puf-A residues 289-297 (RTLDKVLEV) has been classified as minor histocompatibility antigen HA-8 (17), which is associated with an increased risk of graft-versus-host disease (18,19). Zebrafish Puf-A is involved in the development of eyes and primordial germ cells (20).…”

Review of Genetic Variation as a Predictive Biomarker for Chronic Graft-Versus-Host-Disease After Allogeneic Stem Cell Transplantation

“…However, mismatching of mHAs may be useful for directing GvL effect toward e.g. cells of hematopoietic origin (114,115). The mHAs identified so far can be regarded as special cases of concept of whole genome histocompatibility, encompassing all immunogenic amino acid differences between allo-HSCT pairs, as discussed in the next sub-chapter.…”