Origin of Plasma Cell-free DNA after Solid Organ Transplantation

Abstract

Despite current interest in the biology and diagnostic application of plasma cell-free DNA (1), there is little knowledge regarding the cellular origin of this DNA. Recently, we have used a sex-mismatched bone marrow transplantation model to study the relative contributions of hematopoietic and nonhematopoietic cells to circulating DNA (2). We have demonstrated that the predominant proportion of plasma DNA originates from the hematopoietic system (2). However, the proportions of cell-free plasma DNA originating from other organs (e.g., heart, liver, and kidneys) remain unknown. We therefore investigated the contribution of the heart, liver, and kidneys to circulating DNA with use of sex-mismatched heart, liver, and renal transplantation models, respectively. Sex-mismatched heart, liver, and renal transplantation patients were recruited for the study. Twenty-one patients who had received heart transplants were recruited from the Grantham Hospital, Hong Kong. Fourteen of these heart transplantation patients were females with male donors, whereas the remaining 7 were males with female donors. Four sex-mismatched liver transplantation patients at the Pediatric Surgical Unit of the Department of Surgery, Prince of Wales Hospital were recruited; two of these patients were females with male donors and the other two were males with female donors. Six sexmismatched renal transplantation patients were recruited from the Department of Medicine and Therapeutics of …