Background: A 17 year old patient with cystic fibrosis (HLA-A11⁺, CMV^–) underwent bilateral sequential lung transplantation (donor: HLA-A32⁺, CMV⁺). Immunosuppression (IS) consisted of Tacrolimus, MMF and Prednisone. After an uneventful postoperative course of 3 months, he developed histology-proven cutaneous GvHD that was treated successfully by withdrawal of MMF. He developed acute rejection treated by a steroid pulse. While lung function returned to normal, the patient developed CMV infection despite valganciclovir prophylaxis.

Methods: Frequencies of HLA-A32⁺ donor lymphocytes were measured by FACS. ELISpots were performed to detect allospecific (rejection vs. GVHD) and CMV-specific T cells. HLA-A2/NLV-pentamer staining was used to measure frequencies of CMV-specific CD8⁺ CTL. Plasma cytokines were measured by multiplex assays.

Results: With development of skin GvHD, frequencies of 3-4% HLA-A32⁺ donor CD4⁺,CD8⁺ T cells, 5-8% B cells and 1-4% NK cells were detected for 2 weeks. Donor T, NK cells declined after MMF withdrawal; B cell frequencies remained stable. Simultaneously to improvement of GVHD, acute rejection developed, accompanied by a significant increase in frequency of allo-A32-specific CD8⁺ T cells within one week, which declined upon steroid pulse. Allo-HLA-A11-restricted T cells, responsible for GvHD, were found only in a low frequency. With serological detection of CMV, the frequency of HLA-A2/NLV specific CD8⁺ CTL increased and remained stable for four months. CMV infection disappeared with the emergence of CMV-specific CTL. Plasma levels of sCD25, IFN-g, IL-17 responded to IS alterations, to pulsed steroids with a transient drop.

Conclusions: Using specific immune monitoring tools, we could confirm clinical diagnoses of the patient. Frequencies of allo- or virus specific T cells, donor lymphocytes and plasma cytokine levels followed the clinical course of GVHD, followed by rejection followed by CMV infection. The modification of IS by using immune monitoring information resulted in a full recovery of the patient who is still asymptomatic several months after these complications.

CITATION INFORMATION: Falk C, Nicolaus S, Carsten M, Igor T, Wiebke S, Kerstin D, Jana K, Gesine H, Axel H, Gregor W. Immune Monitoring-Guided Treatment of a Pediatric Patient with Sequential GvHD, Acute Rejection and CMV Infection Following Lung Transplantation. Am J Transplant. 2017;17 (suppl 3).

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