Real-time Epstein-Barr virus PCR for the diagnosis of primary EBV infections and EBV reactivation.
BACKGROUND
The serological diagnosis of primary Epstein-Barr virus (EBV) infections is often difficult, whereas the relevance of elevated immunoglobulin G (IgG) antibodies against early antigen (EA) for the diagnosis of EBV reactivation has increasingly become a matter of dispute. Recently, EBV PCR has been added as a diagnostic tool. Positive EBV PCR has been demonstrated in the serum of patients with primary EBV infections and EBV reactivation.


OBJECTIVE
To compare classical serological diagnosis of primary EBV infection and EBV reactivation with real-time EBV PCR.


METHODS
Sera from 45 patients were selected with detectable immunoglobulin M (IgM) antibodies against EBV viral capsid antigen (VCA), and 62 sera were selected with a reactivation profile. A real-time EBV PCR was performed with DNA extracted from these sera.


RESULTS
Based on serological data, the diagnosis of primary EBV infection was established for 24 of the 45 IgM VCA-positive patients. By performing PCR, seven extra cases of primary infection were diagnosed for which no heterophilic antibodies could be detected. In five cases of primary infection, no EBV DNA could be detected by PCR. Only in two of the 62 sera with a reactivation seroprofile could EBV DNA be detected.


CONCLUSIONS
Based on these data, we suggest that for the diagnosis of primary infections, EBV PCR could lead to an increase of >16% in the number of positive diagnoses by confirming a positive IgM VCA in the absence of heterophilic antibodies. Furthermore, EBV PCR is positive in only 3% of sera with elevated antibodies against EA, raising doubt as to the utility of EA titers for diagnosing EBV reactivation.
Luderer
Rianne
R
Unit Molecular Diagnostics, Diakonessenhuis Utrecht, Utrecht, The Netherlands. rluderer@diakhuis.nl
Kok
Marieke
M
Niesters
Hubert G M
HG
Schuurman
Rob
R
de Weerdt
Okke
O
Thijsen
Steven F T
SF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014775:Virus Activation
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; C041788:Epstein-Barr viral capsid antigen; D007074:Immunoglobulin G; D007075:Immunoglobulin M