1004. CMV-specific CD4 and CD8 Responses Are Sensitive Markers for New Onset CMV Infections Among D+/R- Lung Transplant Patients (LTx Pts) and Identify Those Who Are Protected from CMV Relapse after Antiviral Therapy 
Session: Poster Abstract Session: CMV and Transplantation
Saturday, October 22, 2011
Room: Poster Hall B1
Background: D+/R- LuTx pts are at high risk for CMV infections.  The role of CMV-specific T cell profiling in assessing risk for CMV infection among these pts is undefined.

Methods: Prospective observational study of D+/R- LuTx pts.  CD4 and CD8 cells producing IFNγ, TNFα or IL2 in response to MHC I, pp65 and IE-1 peptides and CMV lysate were enumerated in whole blood by flow cytometry.

Results: 20 D+/R- LuTx pts were enrolled; all received induction immunosuppression and tacrolimus/MMF/prednisone.   50%, 25% and 25% of pts developed viremia, CMV disease or no infection, respectively.  In absence of breakthrough CMV infection, no pts mounted CMV T cell responses while on VGC px.   18 pts had VGC px discontinued after ≥ 6 mos.  Among these pts, median CD4-TNFα and -IFNγ and CD8-TNFα and -IFNγ responses against lysate were higher for those with subsequent CMV infection than no infection (CD4: p=0.009 and 0.03, respectively; CD8: p=0.06 and 0.04).  Sensitivity, specificity and LR for CMV infection at cut-offs identified by ROC analysis were:  CD4-TNFα (100%, 86%, 7 at >0.46%); CD4-IFNγ (75%, 86%, 5.2 at >0.12%); CD8-TNFα (75%, 86%, 5.2 at >0.5%); CD8-IFNγ (75%, 86%, 5.2 at >0.06%).  T cell responses against peptides did not correlate with outcomes.  6 pts with CMV infection had serial testing, 4 of whom had low-CD4 IFNγ response (<0.12%) at onset but high response at > 3 mos; antivirals were stopped with no recurrences.  2 pts had either a high CD4-IFNγ response at onset but subsequent low response or a persistently low response.  Both pts relapsed after antivirals were stopped.

Conclusion: Development of CMV-specific CD4 and CD8 responses among D+/R- LuTx pts who have discontinued VGC px may identify pts with CMV infections earlier than PCR.  Adequate CD4-IFNγ responses 3 months after CMV infection appear protective against relapse after antiviral therapy is discontinued.

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.