IMPACT OF PRE-TRANSPLANT THYMOGLOBULIN THERAPY ON IMMUNE RESPONSES IN LUNG TRANSPLANT RECIPIENTS.

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IMPACT OF PRE-TRANSPLANT THYMOGLOBULIN THERAPY ON IMMUNE RESPONSES IN LUNG TRANSPLANT RECIPIENTS.
Kathy J. Spichty, BS , Kenneth R. McCurry, MD , Alin L. Girnita, MD , Diana B. Zaldonis, BSN , Kevin K. McDade, BS , Aldo T. Iacono, MD , Samuel A. Yousem, MD and Adriana Zeevi PhD . Pittsburgh PA, University of Pittsburgh, 15261, Pathology ; Surgery and Pulmonary Medicine .

Since the 5 year survival of lung transplant (LTx) recipients is the lowest of all transplanted organs, a new therapeutic protocol was initiated using Thymoglobulin preconditioning and Tacrolimus mono-therapy. The aim of this study was to evaluate the immune response of 20 consecutive LTx recipients for at least 6 months post-Tx.
Methods: The immune monitoring consisted of sequential assessment of: T, B, and NK cell subsets; immuno-competence (Con A and PHA proliferation); humoral sensitization by ELISA; direct alloreactivity to donor and third party panel cells; TaqMan analysis for pro-inflammatory mediators (Granzyme B, IL-15, IFN-γ, TNF-α, MCP-1 and RANTES ) in bronchoalveolar lavage cells.
Results: Immediately post-Tx we observed a sharp decline of T cell subsets. The recovery of CD8+ T cells occurred earlier than the CD4+ T cells and the latter was still below the pre-Tx levels after 4 months post surgery. Con A and PHA responses recovered at 3-4 months post-Tx, however the ratio of PHA/Con A was reversed (Con A responses were 2-3 fold higher than PHA). 5/20 recipients exhibited anti-HLA antibodies (3 de-novo, 4 donor-specific). The MLR responses to both donor and third party cells tested 4-6 months post-Tx were diminished compared to pre-Tx responses. In 6 patients evaluated by TaqMan early post-Tx, MCP1 and RANTES (macrophage activation mediators) were the most informative.
Conclusions: The current strategy of T cell reduction leads to minimizing post-tx immunosuppression (steroid sparing). The sequential evaluation of cellular and humoral immunity will facilitate the long term management of these patients by identification of risk factors associated with recurrent and refractory rejection.