CLINICAL SPECTRUM OF LYMPHOPROLIFERATIVE DISORDERS IN RENAL-TRANSPLANT RECIPIENTS AND EVIDENCE FOR THE ROLE OF EPSTEIN-BARR VIRUS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (11) , 4253-4261
Abstract
Six renal transplant recipients with abnormal lymphoproliferative disorders were studied in an attempt to define their clinical features and the role of Epstein-Barr virus (EBV) in their pathogenesis. Patients were either teenage (3) or in the 6th decade (3). The younger patients presented an average of 3 mo. after transplantation with fever, sore throat and lymphoadenopathy; were markedly immunosuppressed; and frequently had preceding or concomitant cytomegalovirus infections. Two of 3 had a rapidly fatal course. The older patients presented an average of 5 yr after transplantation while on maintenance immunosuppressive drugs; and had a more indolent, but frequently fatal clinical course. Two of 3 cases presented with an oropharyngeal tumor. The most frequent sites of bbiopsy-proven involvement in these patients were lymph nodes (3), the oropharynx (3), liver (3), bone marrow (3), transplanted kidney (3), colon (2) and CNS (2). EBV-specific antibody titers including anti-viral capsid antigen IgG, anti-viral capsid antigen IgM, anti-early antigen and anti-Epstein-Barr nuclear antigen were serially measured in all patients. Four patients demonstrated serological evidence of a primary (1) or reactivation (3) EBV infection. No patient had significant changes in anti-early antigen or anti-Epstein-Barr nuclear antigen titers. All 3 patients tested for oropharyngeal shedding of EBV were positive. A touch imprint of 1 tumor was stained for the presence of Epstein-Barr nuclear antigen and a majority of cells were positive. EBV complementary RNA/DNA filter hybridization and/or viral DNA/DNA reassociation analysis performed on tumor biopsy specimens in 5 patients demonstrated multiple EBV genome equivalents per cell in all 8 specimens tested. Clinical, pathological, serological and molecular hybridization studies provide substantial evidence that EBV was the cause of these lymphoproliferative disorders occurring after renal transplantation. Impaired host defenses allow the EBV-transformed B-lymphocytes to escape normal control mechanisms. This impairment is variable and influenced by many factors resulting in the observed spectrum of disease. Cytogenetic changes may also be important.