Natural killer cell HLA-C epitopes and killer cell immunoglobulin-like receptors both influence outcome of mismatched unrelated donor bone marrow transplants.

Abstract	Matching of donor and recipient for the class I human leukocyte antigen-C (HLA-C)-encoded natural killer (NK) epitopes has been reported to influence stem-cell (SC) graft outcome, but a consistent picture has not yet emerged. We have analyzed transplant outcome in 104 unrelated SC grafts in relation to NK epitope (C1 and C2) matching and donor killer cell immunoglobulin-like receptor (KIR) genotype. NK epitope mismatching in the rejection direction was strongly associated with an increased probability of rejection subsequent to engraftment. The prevalence of grades III-IV acute graft-vs-host disease (GVHD) was significantly higher and occurred significantly earlier when there was NK epitope mismatching in the GVH direction. Higher transplant-related mortality and lower disease-free survival rates were associated with epitope mismatching regardless of the mismatch direction. A greater number of KIR receptors, both activating and inhibitory, in the donor protected against grades III-IV GVHD and improved survival.
Authors	D De Santis, A Bishara, C S Witt, A Nagler, C Brautbar, S Slavin, F T Christiansen
Journal	Tissue antigens (Tissue Antigens) Vol. 65 Issue 6 Pg. 519-28 (Jun 2005) ISSN: 0001-2815 [Print] England
PMID	15896199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Epitopes HLA-C Antigens Receptors, Immunologic Receptors, KIR
Topics	Adolescent Adult Bone Marrow Transplantation (methods) Child Child, Preschool Disease-Free Survival Epitopes (chemistry) Female Genes, MHC Class I (immunology) Genotype Graft vs Host Disease HLA-C Antigens (immunology) Histocompatibility Testing Humans Infant Killer Cells, Natural (cytology, immunology) Male Middle Aged Polymorphism, Single-Stranded Conformational Receptors, Immunologic (chemistry, physiology) Receptors, KIR Recurrence Stem Cell Transplantation Time Factors Transplantation Conditioning Transplantation Immunology Treatment Outcome

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