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.
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: D-F Chen; V K Prasad; G Broadwater; N L Reinsmoen; A DeOliveira; A Clark; K M Sullivan; J P Chute; M E Horwitz; C Gasparetto; G D Long; Y Yang; N J Chao; D A Rizzieri Journal: Bone Marrow Transplant Date: 2011-12-05 Impact factor: 5.483
Authors: Joy Hsu; Jonathan J Hodgins; Malvika Marathe; Chris J Nicolai; Marie-Claude Bourgeois-Daigneault; Troy N Trevino; Camillia S Azimi; Amit K Scheer; Haley E Randolph; Thornton W Thompson; Lily Zhang; Alexandre Iannello; Nikhita Mathur; Karen E Jardine; Georgia A Kirn; John C Bell; Michael W McBurney; David H Raulet; Michele Ardolino Journal: J Clin Invest Date: 2018-09-10 Impact factor: 14.808
Authors: Hemalatha G Rangarajan; Marcelo S F Pereira; Ruta Brazauskas; Andrew St Martin; Ashleigh Kussman; Ezgi Elmas; Michael R Verneris; Shahinaz M Gadalla; Steven G E Marsh; Sophie Paczesny; Stephen R Spellman; Stephanie J Lee; Dean A Lee Journal: Transplant Cell Ther Date: 2021-08-15
Authors: Izabela Nowak; Edyta Majorczyk; Andrzej Wiśniewski; Andrzej Pawlik; Maria Magott-Procelewska; Ewa Passowicz-Muszyńska; Jacek Malejczyk; Rafał Płoski; Sebastian Giebel; Ewa Barcz; Aleksandra Zoń-Giebel; Andrzej Malinowski; Henryk Tchórzewski; Arkadiusz Chlebicki; Wioleta Łuszczek; Maciej Kurpisz; Marian Gryboś; Jacek Wilczyński; Piotr Wiland; David Senitzer; Ji-Yao Sun; Renata Jankowska; Marian Klinger; Piotr Kuśnierczyk Journal: PLoS One Date: 2010-08-26 Impact factor: 3.240