RESUMEN
Killer immunoglobulin-like receptors and their human leukocyte antigen class I ligands have a critical role in natural killer cell response to viral pathogens and tumors. To investigate whether killer immunoglobulin-like receptor genes could influence the chronic course of hepatitis C virus infection and/or progression to hepatocellular carcinoma we retrospectively analyzed a cohort of 228 patients transplanted for hepatitis C virus-induced cirrhotic end stage liver disease, combined or not with hepatocellular carcinoma. We found that patients completely lacking activating killer immunoglobulin-like receptor genes had a high risk of developing hepatocellular carcinoma. Hepatitis C viral genotype and viral load are other risk factors that can influence the course of chronic hepatitis C virus infection. In our study, the risk conferred by hepatitis C viral genotypes was enhanced in patients lacking activating killer immunoglobulin-like receptors. These results point to an important role for activating killer immunoglobulin-like receptors in the control of hepatitis C virus infection and progression to hepatocellular carcinoma. In clinical practice, assessment of killer immunoglobulin-like receptor and hepatitis C viral genotype combinations should allow for more accurate monitoring of patients with chronic hepatitis C virus infection.
Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Genotipo , Hepatitis C Crónica/complicaciones , Hepatitis C/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Receptores KIR/genética , Adulto , Anciano , Carcinoma Hepatocelular/inmunología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Haplotipos , Hepatitis C Crónica/virología , Antígenos de Histocompatibilidad/genética , Antígenos de Histocompatibilidad/inmunología , Humanos , Ligandos , Cirrosis Hepática/etiología , Neoplasias Hepáticas/inmunología , Masculino , Persona de Mediana Edad , Receptores KIR/inmunología , Estudios Retrospectivos , Carga ViralRESUMEN
In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin-like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft-versus-host disease (GvHD) [hazard risk (HR) 4.2, 95% confidence interval (CI) 1.7-10.1, P = 0.002] and transplantation-related mortality (HR 4.7, 95% CI 1.6-14.2, P = 0.01). The risk of GvHD furthermore increased when recipients heterozygous for HLA-C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6.1, 95% CI 1.9-19.2, P = 0.002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA-KIR ligand group and the donor carried two or more activating KIRs (HR 6.8, 95% CI 1.9-24.4, P = 0.005). By interpolating the number of donor activating KIRs with recipient HLA-C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision-making.
Asunto(s)
Algoritmos , Trasplante de Células Madre Hematopoyéticas , Antígenos de Histocompatibilidad Clase I/genética , Receptores KIR/genética , Talasemia/genética , Talasemia/terapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Frecuencia de los Genes , Técnicas de Genotipaje , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/genética , Haplotipos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Antígenos de Histocompatibilidad Clase I/inmunología , Prueba de Histocompatibilidad , Humanos , Lactante , Ligandos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Unión Proteica/inmunología , Receptores KIR/inmunología , Estudios Retrospectivos , Talasemia/diagnóstico , Donante no Emparentado , Adulto JovenAsunto(s)
Miastenia Gravis/inmunología , Miastenia Gravis/fisiopatología , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Adulto , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Femenino , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Masculino , Miastenia Gravis/genética , LinajeRESUMEN
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-Cw(Asn80)) and 2 (HLA-Cw(Lys80)) 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.
Asunto(s)
Antígenos HLA-A/inmunología , Antígenos HLA-C/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Receptores KIR/genética , Talasemia beta/genética , Talasemia beta/terapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Genotipo , Enfermedad Injerto contra Huésped , Antígeno HLA-A11 , Trasplante de Células Madre Hematopoyéticas/métodos , Prueba de Histocompatibilidad , Humanos , Estimación de Kaplan-Meier , Masculino , Receptores KIR/sangre , Estudios Retrospectivos , Trasplante Homólogo/efectos adversosRESUMEN
BACKGROUND: The incidence of classic Kaposi's sarcoma (CKS) in northern Sardinia is one of the highest in the world. METHODS: Sixty-two patients with CKS were typed for class I and class II antigens. All patients had been born and were living in northern Sardinia. RESULTS: In the Sardinian patients, we observed a positive CKS association with Cw7, DRB1*1104, DRB1*1302, DQA1*0302, and DQB1*0604, and a negative CKS association with A30, B58, Cw5, DRB1*1601, and DQB1*0502. CONCLUSIONS: The strong positive CKS association with DRB1*1104 and DQB1*0604 and negative association with B58 are particularly significant and further support the notion of a genetic predisposition to CKS.