engleski

MINOR HISTOCOMPATIBILITY ANTIGENS IN STEM CELL TRANSPLANTATION FROM HLA IDENTICAL SIBLING

Minor histocompatibility antigens (mHAgs) are polymorphic, endogenously synthesized products that can be recognized by alloreactive T cells in the context of major histocompatibility complex (MHC) molecules. Recipients of allogeneic bone marrow grafts run the risk of graft-versus-host disease (GvHD), even when the donor is HLA-identical sibling. These may arise from disparities in mHAgs between donor and recipient, with the antigen present in the recipient and not in the donor. In such cases, T cells in the transplanted donor marrow respond to mHAgs in the recipient. The minor Histocompatibility Workshop 2005 has been organized in order to provide insight into mHAgs frequencies in healthy population and to evaluate the relevance of mHAgs matching/mismatching for clinical outcome in HLA-matched stem cell transplantation. Tissue Typing Center Zagreb is one out of 27 participating laboratories worldwide. We have typed 93 healthy individuals obtaining for the first time genotype frequencies for the 11 mHAgs studied, which provides the database for the analysis of mHAgs immunogenicity in HLA typed donor/recipient pairs. In addition, we have typed 10 HLA identical sibling donor/recipient pairs, positive for HLA-A2 allele. The potentially relevant mHAgs for these pairs are HA-1, HA-2 and HA-8 antigens. The HA-1, and HA-8 antigens fulfill both conditions for the induction of GVHD: they are immunogenic and have a moderate phenotypic frequency (65% and 63% respectively) in the healthy Croatian population. HA-2 has a phenotypic frequency of 92%, therefore it is not relevant in the majority of pairs. Three pairs were mismatched for HA-1 antigen, two were mismatched for HA-8 and one pair was mismatched for HA-2 and HA-8. Four pairs where matched for HA-1, HA-2 and HA-8 antigens. Correlation between GvHD and matching/mismatching for mHAgs can not be withdrawn yet. The plan is to include up to 50 pairs until the end of the workshop.

minor histocompatibility antigens; BMT

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