Status of Donor-Recipient HLA Class I Ligands and Not the KIR Genotype Is Predictive for the Outcome of Unrelated Hematopoietic Stem Cell Transplantation in Beta-Thalassemia Patients
| Autor: | M Mulargia, Claudio Giardini, Giovanni Caocci, Giorgio La Nasa, Eugenia Piras, Roberto Littera, N Orru, Nesci S, Sandro Orru, Daniela Lisini, Carlo Carcassi, Giada Giustolisi, Adriana Vacca, Arianna Ventrella, Franco Locatelli |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Adolescent Genotype medicine.medical_treatment Thalassemia KIR genotypes KIR ligands KIRS NK cell alloreactivity Unrelated BMT Graft vs Host Disease chemical and pharmacologic phenomena HLA-C Antigens Kaplan-Meier Estimate Human leukocyte antigen Hematopoietic stem cell transplantation Disease HLA-A11 Antigen Receptors KIR immune system diseases medicine Humans Transplantation Homologous Child Retrospective Studies Transplantation HLA-A Antigens business.industry Histocompatibility Testing beta-Thalassemia Hematopoietic Stem Cell Transplantation Beta thalassemia Hematology medicine.disease surgical procedures operative medicine.anatomical_structure Child Preschool Relative risk Immunology Female Bone marrow business |
| Popis: | Several studies have investigated the role played by killer immunoglobulin-like receptors (KIRs) and their ligands on the outcome of hematopoietic stem cell transplantation (HSCT) in patients affected by oncohematologic diseases. However, the interpretation of the results of these studies is considerably hampered by the heterogeneity of the diseases, disease status at transplantation, and the different protocols employed for both conditioning and graft-versus-host disease (GVHD) prophylaxis. To better define the role of KIRs in HSCT, we studied KIR genotypes and HLA class I ligands in a homogeneous group of 45 thalassemia patients transplanted with bone marrow cells from an HLA-identical, unrelated donor. Patients that were heterozygotes for HLA-Cw groups 1 (HLA-CwAsn80) and 2 (HLA-CwLys80) had a higher risk of developing acute GVHD than C1/C1 or C2/C2 homozygotes (relative risk [RR] = 8.75; 95% confidence interval [CI]: 1.63-46.76; P = .007). Vice versa, all patients who experienced primary/secondary graft failure were C1/C1 or C2/C2 homozygotes (RR = 20.45; 95% CI = 1.08-384.24; P = .009). Moreover, the presence of the HLA-A11 antigen conferred protection against GVHD (0% versus 35%, P = .02). Our results suggest that C1/C2 heterozygosity, may favor the development of donor alloreactivity and thereby increase the risk of GVHD. Conversely, C1/C1 and C2/C2 homozygosity seems to reduce the risk of GVHD but may increase the incidence of graft rejection. These data may be helpful in tailoring the intensity of GVHD prophylaxis and conditioning regimens in thalassemia patients receiving HSCT from an HLA-identical volunteer donor. |
| Databáze: | OpenAIRE |
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