402. Single Nucleotide Polymorphism (SNP) Associated with Elevated IFN-γ Levels is a Risk Factor for CMV Disease in Non-mismatch Lung Transplant (LT) Recipients
Session: Poster Session: Hospital-acquired and Transplant Infections
Friday, October 30, 2009: 12:00 AM
Room: Poster Hall A
Background: CMV mismatch (D+/R-) is a leading risk factor for CMV disease. Decreased levels of Th1-type cytokines are linked to CMV replication. We studied clinical and genetic risk factors for CMV disease in LT.
Methods: Retrospective review of 239 LT patients (pts) of European ancestry from 2003-08 for whom DNA was available. All pts received alemtuzumab induction, and valganciclovir (VAL) prophylaxis for > 6 months. CMV infection was defined as viremia or disease (syndrome, tissue invasion). SNPs were detected for TNF-α, TGFβ1, IL-6, IL-10 and IFN-γ genes.
Results: 21% (51/239) were CMV mismatch and 79% non-mismatch. 9% (21) had CMV disease (all pneumonia; mismatch=13), 55% of whom were infected with resistant CMV (UL97). 20% received augmented immunosuppression within 3 mos of CMV disease. The time from LT to onset of CMV disease was similar for mismatch and non-mismatch pts (median: 236 d, range: 44-834). The timeline of disease was: 5% within 1st 3 mos, 14% 3-6 mos, 67% 6-12 mos, 9% 12-18 mos, and 5% >18 mos. 68% developed CMV disease within 3 mos of stopping VAL. Mismatch was a risk factor for CMV disease (p<0.001), but rejection, augmented immunosuppression and age were not. Genotypes were in HW equilibrium. SNP associated with elevated IFN-γ (45% disease vs. 17% viremia/controls, p=0.005) was associated with CMV disease. The association was seen exclusively among non-mismatch pts (62% vs. 16%, p=0.005). Among mismatch pts, associations were not significant. There were no significant associations between SNPs and rejection.
Conclusion: As anticipated, CMV mismatch was a risk factor for CMV dz. Surprisingly, elevated IFN-γ SNP was associated with disease among non-CMV mismatch pts. The results suggest that late-onset CMV disease in non-mismatch pts receiving alemtuzumab and VAL might reflect heightened pulmonary inflammatory responses. The data suggest a model in which CMV disease results from either insufficient immunity, as in mismatch pts, or overexuberant Th1 inflammatory responses, as might be seen in some non-mismatch pts.
Cornelius Clancy, MD1, Dm Girnita, MD, PhD2, Dimitra Mitsani, MD2, M. Hong Nguyen, MD2, Adriana Zeevi, PhD2 and  D. Mitsani, None..
M. Nguyen, None..
A. Zeevi, None..
D. Girnita, None..
C. J. Clancy, None., (1)University of Pittsburgh and VA Pittsburgh, Pittsburgh, PA, (2)UPMC, Pittsburgh, PA