Activating killer immunoglobulin-like receptor incompatibilities enhance graft-versus-host disease and affect survival after allogeneic hematopoietic stem cell transplantation.

Abstract

OBJECTIVES:

Killer immunoglobulin-like receptors (KIRs) regulate function of natural killer (NK) cells and a subset of T cells. In this study, we prospectively evaluated the impact of donor and recipient activating KIR genes on outcome of allogeneic hematopoietic stem cell transplantation (alloHSCT) for patients with hematological malignancies.

METHODS:

One-hundred consecutive recipients of myeloablative transplantation and their donors were tested for KIR genotype as well as for immune reconstitution, including activating KIR expression on NK cells and T cells.

RESULTS:

In a multivariate analysis, mismatches of particular activating KIRs such that the patient was negative and the donor was positive (P-D+) resulted in increased risk of acute (KIR2DS1) and chronic (KIR2DS3) graft-versus-host disease (GVHD) as well as relapse (KIR2DS5). KIR2DS1 incompatibility in the same direction in the presence of HLA-C-group 2 ligand in recipient was associated with reduced overall (risk ratio, RR = 3.01; P = 0.01) and disease-free survival (RR = 2.92, P = 0.03). Activating mismatches in P-D+ direction resulted in decreased CD4+ : CD8+ T-cell ratio up to 1 yr after alloHSCT, as a consequence of decreased CD3+CD4+ number within the first 100 d and increased CD3+CD8+ number in later time-points. Among six evaluated patients, expression of activating KIRs on NK cells and T cells was particularly prominent for those developing intestinal GVHD.

CONCLUSION:

Our findings indicate that the presence of particular activating KIRs in donor with their absence in recipient enhances GVHD, which is not accompanied by graft-versus-leukemia effect. Evaluation of activating KIR genotype may allow optimization of both donor selection and transplantation procedure in order to avoid GVHD.

• Authors: Sebastian Giebel, Izabela Nowak, Joanna Dziaczkowska, Tomasz Czerw, Jerzy Wojnar, Malgorzata Krawczyk-Kulis, Jerzy Holowiecki, Aleksandra Holowiecka-Goral, Miroslaw Markiewicz, Malgorzata Kopera, Agnieszka Karolczyk, Slawomira Kyrcz-Krzemien, Piotr Kusnierczyk
• Journal: European journal of haematology (Eur J Haematol) Vol. 83 Issue 4 Pg. 343-56 (Oct 2009) ISSN: 1600-0609 [Electronic] England
• PMID: 19500138 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• KIR2DS1 protein, human
• KIR2DS3 protein, human
• KIR2DS5 protein, human
• Receptors, KIR

Topics

• Adolescent
• Child
• Child, Preschool
• Genotype
• Graft vs Host Disease (etiology, immunology)
• Hematologic Neoplasms (therapy)
• Hematopoietic Stem Cell Transplantation (adverse effects, mortality)
• Histocompatibility
• Humans
• Infant
• Receptors, KIR (genetics, immunology)
• Survival Analysis
• Transplantation, Homologous
• Treatment Outcome