Clinical usefulness of Epstein-Barr viral load in solid-organ transplantation

Abstract

Epstein‐Barr virus (EBV) DNA was quantitated in peripheral blood mononuclear cells (PBMC) from 25 healthy subjects, 105 asymptomatic solid‐organ transplant (SOT) recipients, and 15 SOT recipients with symptomatic EBV infections by using a newly developed quantitative‐PCR technique. Patients with symptomatic EBV infections had significantly higher (P < 0.001) median EBV DNA levels than asymptomatic SOT recipients and immunocompetent individuals. In SOT recipients, the positive predictive value of EBV DNA levels of > 1,000 genome equivalents (GE)/0.5 μg of total PBMC DNA was 64.7% for symptomatic EBV infection, while the negative predictive value was 96.1%. In 19 of 32 (59.3%) asymptomatic SOT recipients, EBV DNA levels were consistently below 1,000 GE for as long as 18 months, while 10 of 32 (31.2%) patients had 1,000 to 5,000 EBV GE at least once during follow‐up. In a minority of patients (3 of 32; 9.3%), ≥ 5,000 GE could be detected at least once during follow‐up. Reduction of immunosuppressive treatment decreased EBV DNA levels by ≥ 1 log10 unit in patients with symptomatic EBV infections. Quantification of EBV DNA is valuable for the diagnosis and monitoring of symptomatic EBV infections in SOT recipients.

Detection of Epstein-Barr Virus Genomes in Peripheral Blood B Cells from Solid-Organ Transplant Recipients by Fluorescence In Situ Hybridization

“…Before the occurrence of symptomatic disease there is a period of approximately 2 to 6 weeks when the rising EBV load can be detected by PCR. PTLD is associated with a very high EBV load circulating in the peripheral blood: Ͼ1,000 copies of EBV genomes/10 5 PBLs in most cases and greater than 200 copies/10 5 PBLs with rare exceptions (4,11,12,19,21,23,29,34,36,38,39,46). Resolution of EBV infection in pediatric solid-organ transplant recipients is often accompanied by a persistent high circulating EBV load 2 to 3 orders of magnitude higher than the viral load observed in latently infected immunocompetent individuals.…”

Increased Ig‐null B lymphocytes in the peripheral blood of pediatric solid organ transplant recipients with elevated Epstein‐Barr viral loads

“…A high load of EBV in the peripheral blood (>1000 copies/10 5 PBMCs) is strongly associated with a diagnosis of PTLD (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). This load is at least 2-3 orders of magnitude greater than the viral load measured in normal individuals, and is detected 2-6 wk before patients present with symptoms of PTLD (16,20).…”

Surface Immunoglobulin-Deficient Epstein-Barr Virus-Infected B Cells in the Peripheral Blood of Pediatric Solid-Organ Transplant Recipients

“…Estimates of the incidence of disease range from 0.7% (19) to 32% (7) in various allograft recipients, depending on a number of factors. From a large number of separate studies, it has been shown that the diagnosis of PTLD is also associated with a very high EBV load in the peripheral blood (Ͼ1,000 copies/10 5 peripheral blood mononuclear cells [PBMCs]) (5,6,8,9,10,15,17,18,23,26,29,31,32,35). While healthy immunocompetent adults harbor an average of approximately 0.01 to 0.1 genomes per 10 5 PBMCs (29), PTLD patients typically have viral loads several orders of magnitude greater at the time of diagnosis.…”