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Natural killer-cell receptor polymorphisms and posttransplantation non-Hodgkin lymphoma.
- Source :
-
Blood [Blood] 2010 May 13; Vol. 115 (19), pp. 3960-5. Date of Electronic Publication: 2010 Mar 05. - Publication Year :
- 2010
-
Abstract
- Posttransplantation non-Hodgkin lymphoma is a life-threatening complication after transplantation. Although pharmacologically suppressed adaptive immunity plays a major role in its development, the role of innate immunity in posttransplantation lymphoma is unknown. We assessed the 158 V/F polymorphism in the Fc-gamma receptor 3A gene (FCGR3A), killer cell immunoglobulin-like receptor (KIR) genotype, KIR ligand status, and a single nucleotide polymorphism affecting the production of interferon-gamma (IFN-gamma; +874 A/T) in 236 patients with posttransplantation lymphoma reported to the Collaborative Transplant Study. In addition, polymorphisms in the interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) genes previously associated with lymphoma development were also typed. Using a split-cohort approach, gene/allele frequency was related to the 5-year patient survival after the diagnosis of lymphoma and compared with 100 control solid organ transplant recipients. FCGR3A and KIR genotype significantly influenced survival after diagnosis of posttransplantation lymphoma: the hazard of dying was reduced in homozygous carriers of the high-affinity V allele (hazard ratio 0.49, 95% confidence interval 0.29-0.82, P = .006), whereas carrying a genotype including KIR2DL2/KIR2DS2 increased the risk of dying (hazard ratio 1.49, 95% confidence interval 1.07-2.05, P = .02). KIR ligands and cytokine polymorphisms had no effect on survival. None of the genetic loci analyzed emerged as risk factors for lymphoma development.
- Subjects :
- Adolescent
Adult
Aged
Child
Child, Preschool
Cohort Studies
Female
Genotype
Heart Transplantation
Humans
Kidney Transplantation
Killer Cells, Natural pathology
Liver Transplantation
Lymphoma, Non-Hodgkin pathology
Lymphoma, Non-Hodgkin therapy
Male
Middle Aged
Polymerase Chain Reaction
Survival Rate
Young Adult
Interferon-gamma genetics
Lymphoma, Non-Hodgkin genetics
Polymorphism, Single Nucleotide genetics
Receptors, IgG genetics
Receptors, KIR genetics
Receptors, KIR3DL2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 115
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 20207982
- Full Text :
- https://doi.org/10.1182/blood-2009-10-250134