Donor KIR3DL1/3DS1 Gene and Recipient Bw4 KIR Ligand as Prognostic Markers for Outcome in Unrelated Hematopoietic Stem Cell Transplantation

Autor: Katia Gagne, Pascale Perrier, Pascale Loiseau, Dominique Charron, Monique Bois, Colette Raffoux, Isabelle Jollet, L. Absi, Valérie Dubois, Marc Busson, A. Dormoy, Didier Blaise, Marie-Lorraine Balère-Appert, Dominique Masson, Agnès Moine, Jean-Denis Bignon
Přispěvatelé: Etablissement Français du Sang [Nantes], Université de Nantes (UN), Génétique des Anomalies du Développement (GAD), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre France Greffe de Moelle [Saint-Denis La Plaine] (RFGM), Agence de la biomédecine [Saint-Denis la Plaine], Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Etablissement français du sang [Poitiers] (EFS), Etablissement Français du Sang [Grenoble] (EFS), Etablissement français du sang, Auvergne-Loire [Saint-Etienne] (EFS), Etablissement Français du Sang, société francophone de greffe de moëlle et de thérapie cellulaire [Marseille] (SFGM-TC), ARS2000 FRM and FGM group, Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, GAGNE, Katia
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Male
Survival
KIR Ligand
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
KIR3DS1
Hematopoietic stem cell transplantation
Ligands
KIR ligands
0302 clinical medicine
Recurrence
Living Donors
Medicine
Relapse
Child
Bone Marrow Diseases
0303 health sciences
Hematopoietic Stem Cell Transplantation
Receptors
KIR3DL1
Hematology
Middle Aged
Prognosis
KIR genotypes
3. Good health
[SDV] Life Sciences [q-bio]
Killer Cells
Natural
Unrelated hematopoietic stem cell transplantation
Treatment Outcome
Child
Preschool
Hematologic Neoplasms
Histocompatibility
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Killer immunoglobulin-like receptors
KIR3DL1
Adult
Receptors
KIR3DS1
[SDV.IMM] Life Sciences [q-bio]/Immunology
Adolescent
chemical and pharmacologic phenomena
Human leukocyte antigen
HLA-Bw4
Young Adult
03 medical and health sciences
HLA-B Antigens
Humans
Transplantation
Homologous
Retrospective Studies
030304 developmental biology
Transplantation
business.industry
Models
Immunological
Infant
Graft-versus-host-disease
medicine.disease
Survival Analysis
Graft-versus-host disease
Immunology
business
Biomarkers
Follow-Up Studies
030215 immunology
Zdroj: Biology of Blood and Marrow Transplantation
Biology of Blood and Marrow Transplantation, Elsevier, 2009, 15 (11), pp.1366-1375. ⟨10.1016/j.bbmt.2009.06.015⟩
ISSN: 1083-8791
1523-6536
DOI: 10.1016/j.bbmt.2009.06.015⟩
Popis: International audience; Given their antileukemic activity, natural killer (NK) cells can alter the outcome of hematopoietic stem cell transplantation (HSCT). The physiologic functions of NK cells are regulated by the interaction of killer immunoglobulin-like receptors (KIR) with specific HLA class I ligands. In the literature, different models based on HLA class I and/or KIR donor (D)/recipient (R) gene disparities are considered as predictors of NK cell alloreactivity. In this retrospective and multicentric French study, we analyzed the clinical impact of the different NK-alloreactivity models in 264 patients who underwent T repleted unrelated HSCT. First, we did not observe that the ''KIR ligand-ligand'' model had a significant clinical impact on unrelated HSCT outcome, whereas the ''missing KIR ligand'' model had a significant but limited effect on unrelated HSCT, because only the absence of C1 ligand in patients with myelogenous diseases was associated with a decreased overall survival (OS) (hazard ratio 5 2.17, P 5.005). The ''KIR receptor-receptor'' and the ''KIR receptorligand'' models seemed the most capable of predicting NK alloreactivity because they had a significant impact on acute graft-versus-host disease (aGVHD) occurrence, OS, and relapse incidence in D/R unrelated pairs. In particular, KIR3DL1 gene mismatches in the GVH direction (D 1 R 2) and the D KIR3DL1 1 /3DS1 1 and R Bw4 2 combination were respectively correlated with the lowest OS in HLA identical pairs (HR 5 1.99, P 5.02) and the highest incidence of relapse in HLA nonidentical D/R unrelated pairs (HR 5 4.72, P 5.03). Overall, our results suggest a detrimental effect of KIR3DL1 1 /3DS1 1 donor NK cells transplanted into HLA-Bw4 2 patients in the absence of an educational process via KIR3DL1/HLA-Bw4 interactions.
Databáze: OpenAIRE
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