A polymorphism linked to elevated levels of interferon-γ is associated with an increased risk of cytomegalovirus disease among Caucasian lung transplant recipients at a single center

BackgroundSingle-nucleotide polymorphisms (SNPs) associated with active cytomegalovirus (CMV) infections after lung transplantation have not been identified.MethodsSNPs associated with varying levels of interferon (IFN)-γ (+874T/A), tumor necrosis factor-α (−308G/A), interleukin-10 (−1082G/A, −819C/T, −592C/A) and interleukin-6 (−174G/C) were characterized for 170 Caucasian lung transplant recipients who received alemtuzumab induction and valganciclovir prophylaxis against CMV.ResultsPatients were followed for a median of 34 months post-transplant, and 66% (113 of 170), 24% (40 of 170) and 10% (17 of 170) had no CMV infection, CMV viremia and CMV disease, respectively. Median times to CMV viremia and disease were 7 and 10 months, respectively. For each gene, there was no significant deviation from Hardy–Weinberg equilibrium. Independent risk factors for the development of CMV disease were IFN-γ +874 T/T genotype (associated with high levels of IFN-γ production), CMV donor-positive/recipient-negative (D+/R−) serostatus and acute cellular rejection requiring augmented immunosuppression (p = 0.001, 0.003 and 0.049, respectively). The association between IFN-γ +874 T/T genotype and CMV disease was most striking among R+ patients (p = 0.02). D+/R− serostatus was also a significant risk factor for CMV viremia (p = 0.0005). IFN-γ +874 T/T genotype was associated with significantly lower peak CMV viral loads (p = 0.03). There were no associations between tumor necrosis factor-α, interleukin-10 or interleukin-6 SNPs and CMV infections.ConclusionA genetic predisposition to elevated IFN-γ levels may play a dual role in controlling active CMV infection among lung transplant recipients receiving alemtuzumab induction and valganciclovir prophylaxis, limiting the extent of viral replication in serum but increasing the risk of CMV disease. Single-nucleotide polymorphisms (SNPs) associated with active cytomegalovirus (CMV) infections after lung transplantation have not been identified. SNPs associated with varying levels of interferon (IFN)-γ (+874T/A), tumor necrosis factor-α (−308G/A), interleukin-10 (−1082G/A, −819C/T, −592C/A) and interleukin-6 (−174G/C) were characterized for 170 Caucasian lung transplant recipients who received alemtuzumab induction and valganciclovir prophylaxis against CMV. Patients were followed for a median of 34 months post-transplant, and 66% (113 of 170), 24% (40 of 170) and 10% (17 of 170) had no CMV infection, CMV viremia and CMV disease, respectively. Median times to CMV viremia and disease were 7 and 10 months, respectively. For each gene, there was no significant deviation from Hardy–Weinberg equilibrium. Independent risk factors for the development of CMV disease were IFN-γ +874 T/T genotype (associated with high levels of IFN-γ production), CMV donor-positive/recipient-negative (D+/R−) serostatus and acute cellular rejection requiring augmented immunosuppression (p = 0.001, 0.003 and 0.049, respectively). The association between IFN-γ +874 T/T genotype and CMV disease was most striking among R+ patients (p = 0.02). D+/R− serostatus was also a significant risk factor for CMV viremia (p = 0.0005). IFN-γ +874 T/T genotype was associated with significantly lower peak CMV viral loads (p = 0.03). There were no associations between tumor necrosis factor-α, interleukin-10 or interleukin-6 SNPs and CMV infections. A genetic predisposition to elevated IFN-γ levels may play a dual role in controlling active CMV infection among lung transplant recipients receiving alemtuzumab induction and valganciclovir prophylaxis, limiting the extent of viral replication in serum but increasing the risk of CMV disease.