engleski

MINOR HISTOCOMPATIBILITY ANTIGENS HA-1, HA-2 AND HA-8 POLYMORPHISMS IN HLA-IDENTICAL RELATED BONE MARROW TRANSPLANTATION

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. As a part of the minor H antigen component of the 14th IHW, we have typed 100 healthy individuals for the 10 mHAgs. The obtained genotype frequencies, provides the database for the analysis of mHAgs immunogenicity in HLA identical donor/recipient pairs. We have typed 20 HLA identical sibling donor/recipient pairs, positive for HLA-A2 allele. Allele, genotype and phenotype frequencies among donor/recipient pairs were in concordance with the ones obtained for the healthy population. 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. Eight pairs where matched for HA-1, HA-2 and HA-8 antigens. Twelve pairs had mismatches in GvH direction for at least one of the relevant mHAgs (4 for HA-1, 1 for HA-2, 6 for HA-8 and 1 for HA-2 and HA-8). Correlation between GvHD and matching/mismatching for mHAgs revealed that GvHD grade II or higher was equally distributed among matched and mismatched donor/recipient pairs.

HA-1; HA-2; HA-8; HSCT

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