Epstein-Barr virus infection-associated renal disease: diagnostic use of molecular hybridization technology in patients with negative serology.
There are only a few reports of renal disease associated with Epstein-Barr virus (EBV) infection. The diagnosis of EBV infection in these previously reported patients was based primarily on positive serology. Two patients with renal disease who, despite repeatedly negative serologies, were shown by molecular hybridization techniques--in situ hybridization (ISH) and polymerase chain reaction (PCR)--to have EBV infection are reported here. Site-specific molecular probes directed against specific, tandemly repeated EBV genomic regions were used. A synthetic 23-mer terminally biotin-labeled oligonucleotide probe selected from the EBV NotI region was used for ISH. For PCR, oligonucleotide primers were designed from sequences of the highly conserved, long internal direct repeat region of EBV to specifically amplify a 110-base-pair segment. The first patient, a 3-yr-old girl with a 1-yr history of fatigue, fever, splenomegaly, and lymphadenopathy developed hematuria. A renal biopsy revealed widespread glomerular mesangiolysis admixed with segmental mesangial sclerosis; no immune deposits were noted by electron microscopy or immunofluorescence. ISH on paraffin sections of the resected spleen and lymph nodes was positive for EBV. The second patient, a 28-yr-old male renal allograft recipient, received a double dose of OKT3. Seven weeks after transplantation, a renal biopsy revealed a lymphoproliferative disorder. Paraffin sections of the nephrectomy specimen were positive for EBV by both ISH and PCR. It was concluded that (1) EBV cannot be excluded on the basis of multiple negative serologies in some patients, and (2) ISH and PCR may lead to the detection of viral genomic information in renal and nonrenal tissues.