Natural killer-cell receptor polymorphisms and posttransplantation non-Hodgkin lymphoma.
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.
Stern
Martin
M
Immunobiology Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland. sternm@uhbs.ch
Opelz
Gerhard
G
Döhler
Bernd
B
Hess
Christoph
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D016027:Heart Transplantation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000473:pathology; D016031:Liver Transplantation; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D054340:Receptors, KIR / Q000235:genetics*; D054347:Receptors, KIR3DL2 / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult
C496124:FCGR3A protein, human; C433932:KIR2DS2 protein, human; D017452:Receptors, IgG; D054340:Receptors, KIR; D054347:Receptors, KIR3DL2; D007371:Interferon-gamma