The role of killer immunoglobulin-like receptor haplotypes on the outcome of unrelated donor haematopoietic SCT for thalassaemia

• Published in: Bone marrow transplantation (Basingstoke) Vol. 45; no. 11; pp. 1618 - 1624
• Main Authors: Littera, R, Orrù, N, Vacca, A, Bertaina, A, Caocci, G, Mulargia, M, Giardini, C, Piras, E, Mastronuzzi, A, Vinti, L, Orrù, S, Locatelli, F, Carcassi, C, Nasa, G La
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2010; Nature Publishing Group
• Subjects: 631/250/1619/382; 692/699/1541/13; 692/699/249/1529; 692/700/565/545/576/1955; Adolescent; Adult; Anemias. Hemoglobinopathies; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood diseases; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Care and treatment; Cell Biology; Child; Child, Preschool; Complications; Confidence intervals; Cytotoxicity; Disease prevention; Diseases of red blood cells; Female; Gene Frequency; Genotype; Genotyping; Globulins; Graft vs Host Disease - immunology; Graft-versus-host reaction; Haplotypes; Health aspects; Hematologic and hematopoietic diseases; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Histocompatibility antigens; HLA histocompatibility antigens; Humans; Immunoglobulin-like receptors; Immunoglobulins; Infant; Internal Medicine; Killer cell immunoglobulin-like receptors; Killer Cells, Natural - immunology; Ligands; Male; Medical sciences; Medicine; Medicine & Public Health; Natural killer cells; original-article; Prophylaxis; Public Health; Receptors; Receptors, KIR - genetics; Receptors, KIR - immunology; Retrospective Studies; Stem cell transplantation; Stem Cells; Thalassemia; Thalassemia - immunology; Thalassemia - surgery; Thymocytes; Tissue Donors; Toxicity; Transfusion; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Treatment Outcome; Young Adult; Italy; natural killer cells; KIR haplotypes; acute GVHD; thalassaemia; haematopoietic SCT; Hemoglobinopathy; Immunopathology; Graft versus host disease; Prognosis; Hematology; Unrelated donor; Acute; Stem cell; Killer immunoglobulin like receptor; Hematopoietic cell; Homograft; Thalassemia; Hemopathy; Genetic disease; Natural killer cell; Hemolytic anemia; Haplotype; Hematopoietic stem cell transplantation
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2010.24

Recent insight into the pathophysiology of acute GVHD after allogeneic haematopoietic SCT has led to a growing interest in the role of natural killer (NK) cells. NK cell cytotoxicity is mainly regulated by the interaction of activating and inhibitory killer immunoglobulin-like receptors (KIRs) with their respective ligands. To investigate the impact of KIRs and their ligands on haematopoietic SCT outcome, we performed a retrospective study of 78 transfusion-dependent thalassaemia patients (median age 10 years, range 1–29 years) transplanted from an unrelated donor selected using high-resolution molecular typing for both class I and II loci after a myeloablative conditioning regimen. GVHD prophylaxis consisted of CsA, short-term MTX and anti-thymocyte globulin in all patients. We found that patients transplanted from donors homozygous for KIR haplotype A had a greater risk of developing grade II–IV acute GVHD compared with those transplanted from a donor carrying at least one B haplotype (hazard ratio=4.5, 99% confidence interval=1.2–17.1,
P
=0.003). Our study suggests that KIR genotyping of donor and recipient pairs could contribute to the identification of patients at high risk for developing severe complications of haematopoietic SCT and thus may help with the choice of intensity of GVHD prophylaxis.