Indirect recognition of donor HLA class I peptides in lung transplant recipients with bronchiolitis obliterans syndrome.

BACKGROUND: The presentation of donor MHC class II-derived peptides by host antigen-presenting cells in the context of self-MHC class II molecules has been suggested as a mechanism for the chronic rejection of kidney and heart allografts. The aim of this study was to determine whether indirect allorecognition of HLA class I-derived peptides occurred in lung transplant (LTx) recipients and whether it correlated with the development of bronchiolitis obliterans syndrome (BOS). METHODS: Peripheral blood mononuclear cells from LTx recipients were cultured with synthetic peptides corresponding to the hypervariable regions of the mismatched HLA class I antigens of the donor. Proliferation and precursor frequency (PF) of allopeptide reactive T cells were determined by the incorporation of [3H]thymidine into DNA and limiting dilution analysis. RESULTS: Peripheral blood leukocytes of LTx recipients with BOS mismatched for HLA class I molecules showed a proliferative response three- to fourfold higher than those observed in mismatched recipients without BOS and in normal control individuals (P<0.001). Similarly, the PF of allopeptide-reactive T cell was 3- to 24-fold higher in recipients with BOS compared with recipients without BOS (P<0.05) as well as normal control individuals (P<0.03). The T cell PF to donor-specific allopeptides, as well as irrelevant allopeptides, was not significantly different in LTx recipients without BOS and normal control individuals. CONCLUSIONS: These data suggest that T cells from LTx recipients are sensitized to mismatched HLA class I antigens. The sensitization was significantly higher in LTx recipients with BOS compared with LTx recipients without BOS. Strategies to block T-cell responses generated by indirect allorecognition after lung transplantation may provide a means for the prevention or treatment of BOS in LTx recipients.

Tacrolimus therapy for persistent or recurrent acute rejection after lung transplantation.

BACKGROUND: Because the severity, frequency, and duration of acute rejection have been linked to the risk of chronic allograft rejection, controlling persistent or recurrent acute rejection is paramount. Tacrolimus has been effective in the management of recalcitrant rejection in other solid organ transplants, and the initial experience in lung transplantation has been favorable. In this study, the impact of changing from a cyclosporine-based to a tacrolimus-based immunosuppressive regimen in lung transplant recipients with persistent or recurrent acute rejection was analyzed. METHODS: The incidence and severity of acute rejection were retrospectively analyzed in 14 lung transplant recipients who were switched from cyclosporine to tacrolimus maintenance immunosuppression because of persistent or recurrent, biopsy-proven acute rejection. RESULTS: Recipients had been treated for acute rejection an average of 2.6 times before changing from cyclosporine to tacrolimus, and 3 recipients had a course of OKT3 therapy. Tacrolimus therapy was begun 238+/-180 days after transplantation, and the mean follow-up period on tacrolimus treatment was 330+/-201 days. After the changeover from cyclosporine to tacrolimus, the number of episodes of acute rejection per recipient decreased (4.3+/-2.1 to 0.4+/-0.5; p=.0001), the average histologic grade of rejection receded (1.3+/-0.4 to 0.3+/-0.4; p=.0001), and the incidence of acute rejection declined (2.4+/-1.5 to 0.1+/-0.3 episodes per 100 patient-days; p=.0001). CONCLUSIONS: Conversion from a cyclosporine- to a tacrolimus-based maintenance immunosuppressive regimen is an effective approach for managing persistent or recurrent allograft rejection after lung transplantation.

Staging of esophageal cancer with 18F-fluorodeoxyglucose positron emission tomography.

OBJECTIVE: The objective of this study was to assess the performance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in the staging of cancer in patients with esophageal carcinoma. MATERIALS AND METHODS: The findings of FDG PET and of CT in the chest and upper abdomen of 36 patients with newly diagnosed esophageal carcinoma were compared with pathologic findings obtained either during a curative surgical procedure with tissue sampling (n = 29) or by tissue sampling alone (n = 7). RESULTS: Abnormal FDG uptake was identified on PET in the esophageal tumors of all patients. In 29 patients who underwent curative esophagectomy, PET and CT accurately revealed the extent of nodal disease in 76% (22/29) and 45% (13/29) of patients, respectively. In the seven patients who underwent tissue sampling instead of complete esophagectomy, PET revealed metastatic disease in five patients, all of whom avoided needless surgery. CT failed to reveal metastatic disease in these five patients. In addition, PET incidentally revealed an unsuspected primary long carcinoma in one patient. CONCLUSION: FDG PET is more sensitive than CT for revealing regional and distant metastases in patients with esophageal carcinoma. The use of PET in the staging of esophageal cancer may prove to be cost-effective by decreasing the number of unnecessary surgeries in patients with unresectable tumors.