B Cell Abnormalities And Cancer Development In Heart Recipients

Purpose Along with infections, rejection and graft vasculopathy, malignancies comprise a major complication after heart transplant, with a rate of occurrence of over 30% in 10 years. Skin cancers and posttransplant lymphoproliferative disorder are more common in adults. The risk factors for development of a malignancy after heart transplant are the same as for the nontransplant population. Identification of biomarkers that assess post-transplant risk is needed to improve long-term outcomes following heart transplantation. Methods We performed a single center, cohort study of 281 heart transplant recipients followed for a mean time of 9.5 years (2-19 years post-transplant). Mean age was 54.5, male 71.5%. The primary endpoint was development of neoplasia (27.2%). 8.2% developed metastasis. We serially measured funcionally distinct lymphocyte subsets in peripheral blood. We correlated assay results with the outcomes of neoplasia and development of metastasis. Lymphocyte subsets were assessed by four-colour flow-cytometry before transplantation at the time of inclusion in waiting list, at day 7 and 30 after heart transplantation. Results Clinical risk factors of cancer were age, smoking, obesity, ischemic etiology and post-transplant infections. We observed the following abnormalities in heart recipients who developed cancer: lower percentages of naive B-cells and lower mean fluorescence intensity (MFI) of toll like receptor (TLR) 4 on B-cells before transplantation (p=0.01 and p=0.049, respectively); lower non switched memory B-cell percentages and lower MFI of TLR4 on B-cells at 7 days after transplantation (p Conclusion Immunological abnormalities of B-cells and of TLR4 expression on B-cells and CD8 T-cells were observed in heart recipients who developed cancer after heart transplantation. These results suggest a role of these abnormalities in the predisposition to cancer that warrants further evaluation.