Effie W Petersdorf1, John A Hansen. 1. Division of Clinical Research, Fred Huchinson Cancer Research Center, Seattle, Washington 98109, USA. epetersd@fhcrc.org
Abstract
PURPOSE OF REVIEW: The present review highlights sentinel work published since 2006 on the definition of the transplantation barrier and the elucidation of cytokine and immune response gene variation in defining posttransplant risks. RECENT FINDINGS: Recent work has defined the relative importance of matching for the classical human leukocyte antigen (HLA) HLA-A, HLA-B, HLA-C, DRB1, DQB1 genes, and the importance of additive effects of multilocus disparity. This work provides a new framework for donor identification and extends the use of single locus HLA-DQB1 mismatched donors without compromising the success of the transplant. New data demonstrate that permissible class I mismatches may be defined by donor-recipient mismatching at certain residues. The concept that the extended HLA haplotype carries undetected but functional variation provides an approach for mapping novel transplantation determinants, and a means to further improve the clinical results of transplantation from HLA-matched unrelated donors. Finally, the role of sequence variation in immune response and cytokine genes provides a means for assessing risks for a given transplant recipient and may aid in the planning of the transplant procedure. SUMMARY: Optimizing the results of unrelated donor transplantation requires an understanding of risks associated with variation of HLA genes within the major histocompatibility complex, and of genes that participate in the immune response and inflammatory pathways.
PURPOSE OF REVIEW: The present review highlights sentinel work published since 2006 on the definition of the transplantation barrier and the elucidation of cytokine and immune response gene variation in defining posttransplant risks. RECENT FINDINGS: Recent work has defined the relative importance of matching for the classical human leukocyte antigen (HLA) HLA-A, HLA-B, HLA-C, DRB1, DQB1 genes, and the importance of additive effects of multilocus disparity. This work provides a new framework for donor identification and extends the use of single locus HLA-DQB1 mismatched donors without compromising the success of the transplant. New data demonstrate that permissible class I mismatches may be defined by donor-recipient mismatching at certain residues. The concept that the extended HLA haplotype carries undetected but functional variation provides an approach for mapping novel transplantation determinants, and a means to further improve the clinical results of transplantation from HLA-matched unrelated donors. Finally, the role of sequence variation in immune response and cytokine genes provides a means for assessing risks for a given transplant recipient and may aid in the planning of the transplant procedure. SUMMARY: Optimizing the results of unrelated donor transplantation requires an understanding of risks associated with variation of HLA genes within the major histocompatibility complex, and of genes that participate in the immune response and inflammatory pathways.
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