393. SNPs Associated with a High IL-6, Low IL-10 Cytokine Pattern Predispose Lung Transplant (LT) Recipients to Pneumonia due to Moulds
Session: Poster Session: Hospital-acquired and Transplant Infections
Friday, October 30, 2009: 12:00 AM
Room: Poster Hall A
Background: Host immunity is an important outcome determinant for transplant patients (pts) with invasive fungal infections (IFI). In general, Th1 responses are felt to be protective against IFI, and Th2 responses deleterious. We determined if single nucleotide polymorphisms (SNPs) associated with altered cytokine levels predisposed LT pts to invasive fungal pneumonia caused by moulds.
Methods: We retrospectively reviewed the records of 155 LT pts between 2003-2007 who received alemtuzumab induction and consented to genetic studies. Only patients with proven or probable pneumonia due to mould were included in the disease group. Genotypic analysis (SSP-PCR) detected the presence of SNPs in genes encoding TNF-α, TGF-β1, IL-4, IL-6, IL-10 and IFN-γ.
Results: 25 had pneumonia due to moulds, and 130 pts did not develop any fungal infection (controls). All were Caucasians. We excluded 5 patients with mould pneumonia who were treated for acute rejection within 3 months of the diagnosis. No pts with mould pneumonia had CMV infection within 3 months. 60% of pneumonias were caused by Aspergillus, 15% Rhizopus, 15% dematiaceous fungi and 10% other moulds. 55% were men. Mean and median ages were 53 and 56 yrs. 75% were double-LT, 20% single-LT and 5% heart-LT. 40% had COPD, 20% IPF and 10% CF. The time to pneumonia post-LT was <6 mo in 10%, 6-12 mo in 10%, 12-18 mo in 25%, 18-24 mo in 25%, 24-36 mo in 15% and >36 mo in 15%. Genotypes were in HW equilibrium. There was no significant association between SNPs for individual genes and fungal pneumonia. However, the combination of SNPs associated with high level IL-6 and low level IL-10 was significantly more common among patients with pneumonia than controls (40% vs 14%, P<0.01).
Conclusion: Surprisingly, LT pts with SNPs associated with a pro-inflammatory cytokine profile of high IL-6 and low IL-10 were at increased risk of pneumonia due to moulds, independent of acute rejection. Over-exuberant inflammatory responses might contribute to the pathogenesis of late onset fungal pneumonia in pts receiving alemtuzumab.
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