Detection of Epstein-Barr Virus DNA in Sera from Transplant Recipients with Lymphoproliferative Disorders

Abstract

Early diagnosis of Epstein-Barr Virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD) is important because many patients respond to reduction in immunosuppression, especially if PTLD is detected at an early stage. Previous studies have found elevated EBV DNA levels in blood from patients with PTLD, but these assays required isolation of cellular blood fractions and quantitation. We evaluated the presence of cell-free EBV DNA in serum from solid-organ transplant recipients as a marker for PTLD. Five of 6 transplant recipients with histopathologically documented PTLD had EBV DNA detected in serum at the time of diagnosis (sensitivity = 83%), compared with 0 of 16 matched transplant recipients without PTLD (specificity = 100%) (P < 0.001 [Fisher’s exact test]). Furthermore, EBV DNA was detected in serum 8 and 52 months prior to the diagnosis of PTLD in two of three patients for whom stored sera were analyzed. Detection of EBV DNA in serum appears to be a useful marker for the early detection of PTLD in solid-organ transplant recipients. Further studies to define the role of such assays in evaluating solid-organ transplant patients at risk for PTLD are warranted.

Prevention and Treatment of Epstein—Barr Virus Associated Lymphoproliferative Disorders in Recipients of Bone Marrow and Solid Organ Transplants

“…VL detection in cell-free plasma seems to be more accurate: in five out of six studies 100% sensitivity was obtained (Fontan et al, 1998;Beck et al, 1999;Limaye et al, 1999;Ohga et al, 2001; van Esser et al, 2001a;Wagner et al, 2001a). Limaye et al (1999) report the only patient with a negative PCR result in cellfree plasma who was diagnosed with EVB-LPD. However, the only manifestation of EBV-LPD in this patient was a skin nodule.…”

“…In 5 of 13 studies measuring viral load (VL) in PBMC the sensitivity for diagnosing EBV-LPD was less than 100% (Riddler et al, 1994;Rooney et al, 1995a;George et al, 1998;Lucas et al, 1998a,b;Kimura et al, 1999;Baldanti et al, 2000;Hoshino et al, 2001;Stevens et al, 2001;Wagner et al, 2001a,b;Gartner et al, 2002;Sirvent-von Bueltzingsloewen et al, 2002). VL detection in cell-free plasma seems to be more accurate: in five out of six studies 100% sensitivity was obtained (Fontan et al, 1998;Beck et al, 1999;Limaye et al, 1999;Ohga et al, 2001; van Esser et al, 2001a;Wagner et al, 2001a). Limaye et al (1999) report the only patient with a negative PCR result in cellfree plasma who was diagnosed with EVB-LPD.…”

Review of Epstein–Barr virus and post‐transplant lymphoproliferative disorder post‐solid organ transplantation (Review Article)

“…In SOT recipients, the detection of a high EBV viral load (expressed as copies or genome equivalents of peripheral blood lymphocytes or serum EBV DNA) as a marker of PTLD development was associated with a sensitivity of between 39-87% and a specificity of 100%. 63,64 The sensitivity of these tests may be greater in paediatric transplant recipients, especially those who acquired primary EBV infection post-transplant. 65 SOT recipients with EBV-driven PTLD have an EBV viral load >500 copies/10 5 lymphocytes 66 but there is currently no consensus on the 'cut-off value' representative of a positive test and there is no standardisation of PCR assays between centres.…”

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).…”