141. Profiling of CMV-specific CD4 and CD8 Responses in Blood Identifies R+ Lung Transplant Patients (LTx Pts) Who Are Likely to Develop CMV Infection after Discontinuing Antiviral Prophylaxis (Px)
Session: Oral Abstract Session: Clinical Virology and Treatment
Friday, October 21, 2011: 9:30 AM
Room: 156ABC
Background: The role of CMV-specific T cell profiling following LTx is undefined.

Methods: We quantified CD4+ and CD8+ cells producing IFNγ, TNFα or IL2 in response to MHC I, pp65 and IE-1 peptides and CMV lysate in CMV R+ pts at pre-determined time points after LTx, using flow cytometry on whole blood samples. We established cutoffs for protection against CMV viremia after valganciclovir (VGN) px was stopped.

Results: 33 R+ pts were enrolled.  At pre-Tx baseline, median CD4 and CD8 IFNγ responses (1.6 and 1.62%) were higher against lysate than peptides.  All pts received alemtuzumab induction, followed by tacrolimus, MMF and prednisone.  10, 29 and 67% of patients had CD8+ responses against lysate restored to pre-Tx levels by 1, 3 & 6 months, respectively.  Corresponding values for CD4+ responses were 0, 50 & 61%.  22 pts discontinued VGN after ≥ 3 months without evidence of CMV infection. 18% (4/22) and 82% (18/22) of pts developed and did not develop CMV viremia, respectively.  Median CD4+ TNFα, - IFNγ, -IL2 and -IL2/IFN γ responses against lysate were significantly higher among pts who did not develop viremia vs pts who did (p=0.004, 0.03, 0.03 and 0.02, respectively).  Median CD8-IFNγ, -TNFα and -IL2/IFN γ responses against lysate also were higher among pts who did not develop viremia (p=0.002, 0.03 and 0.02, respectively).    Sensitivity, specificity and likelihood ratio (LR) for developing CMV infection based on cut-off CD4 responses (as determined by ROC analysis) were:  CD4-TNFα (100%, 94%, 18 at <0.32%), CD4-IFNγ (100%, 83%, 6 at <0.46%), CD4-IL2 (100%, 78%, 4.5 at <0.36%), and CD4-IL2/IFNγ (100%, 72%, 3.6 at <0.4%).  Sensitivity, specificity and LR for CD8 responses were:  CD8-IFNγ (100%, 89%, 9 at <0.12%), CD8-TNFα (75%, 94%, 13.5 at <0.22%), and CD8-IL2/IFNγ (75%, 78%, 3.4 at <0.01%).  CD4 and CD8 responses against CMV peptides only correlated with outcomes for CD8-IL2/IFNγ against pp65 (p=0.01; 100%, 78%, 4.5 at <0.07%).  A combination of either CD4-TNFα <0.32% or CD8-IFNγ <0.12% was 100% sensitive and specific for predicting CMV viremia (p=0.0001).  

Conclusion: Monitoring CMV-specific CD4 and CD8 responses may identify R+ LTx pts who do not require VGN px beyond 3 months.  CMV T cell monitoring after LTx may shorten VGN px.  Such strategies should be tested in future trials.

Subject Category: O. Transplant infectious diseases

Cornelius Clancy, MD1, Cory Lutgen2, Jin Yu2, Jeff Hester, PhD2, Linda Flebbe-Rehwaldt2, D Mitsani, MD3, Ryan K. Shields, PharmD3 and M. Hong Nguyen, MD3, (1)University of Pittsburgh and VA Pittsburgh, Pittsburgh, PA, (2)ViraCor-IBT, Lee's Summit, MO, (3)University of Pittsburgh, Pittsburgh, PA


C. Clancy, Pfizer: Grant Investigator, Research grant
Merck: Grant Investigator, Research support

C. Lutgen, ViraCor-IBT: Employee, Salary

J. Yu, ViraCor-IBT: Employee, Salary

J. Hester, ViraCor-IBT: Employee, Salary

L. Flebbe-Rehwaldt, ViraCor-IBT: Employee, Salary

D. Mitsani, None

R. K. Shields, Pfizer, Merck, Astellas: , Research grant and Research support

M. H. Nguyen, Pfizer: Grant Investigator, Research support
Merck: Grant Investigator, Research grant

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.