Post-Transplant lymphoproliferative disorder (PTLD)

1

What infectious agent plays a central role in the development of most post-transplant lymphoproliferative disorder and why?

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus transmitted primarily via saliva, is causally involved in most lymphoproliferative disease. Initial infection with EBV occurs during childhood but persists as a latent infection throughout life. EBV colonizes antibody-producing B cells and thus evades recognition and destruction by cytotoxic T cells. EBV infection is largely controlled by memory EBV-specific cytotoxic T lymphocytes (EBV-CTL) and remains an asymptomatic infection in B cells. EBV carries a set of latent genes that induce cellular proliferation when expressed in resting B cells. This cell proliferation when unregulated or accompanied by additional genetic events can lead to malignant transformation. EBV infection in patients with compromised T-cell immunity after transplantation because of immunosuppression leads to the development of post-transplant lymphoproliferative disorder (PTLD). Other DNA viruses such as human immunodeficiency virus (HIV; HTLVIII), human herpesvirus 8 (HHV8, also known as Kaposi sarcoma–associated virus), cytomegalovirus (CMV), and hepatitis C virus (HCV) have also been associated with the development of lymphoproliferative diseases.

2

How does PTLD present clinically?

PTLD involves a diverse spectrum of symptoms, including isolated adenopathy, hepatitis, lymphoid interstitial pneumonitis, meningo-encephalitis, an infectious mononucleosis-like syndrome, or a septic shock–like presentation. Although PTLD can arise after any organ transplant, the cells of origin in patients who have undergone a bone marrow transplant are usually donor cells, whereas in patients who have undergone solid organ transplants (SOT), PTLD arises in cells that are of host origin. Nevertheless, clinical manifestations do not appear to differ by cell of origin.

PTLD appears to arise as a defective response to a viral infection, most commonly EBV. This defective response is in part because of immune dysregulation, stemming from an absence of EBV-CTL. This inability to clear EBV-infected B cells leads to B-cell proliferation with the potential for malignant transformation.

3