Comparison of plasma Epstein-Barr virus (EBV) DNA

levels and serum EBV immunoglobulin A/virus

capsid antigen antibody titers in patients with
nasopharyngeal carcinoma.
Shao JY, Li YH, Gao HY, Wu QL, Cui NJ, Zhang L, Cheng G, Hu LF, Ernberg I,
Zeng YX.

Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.

BACKGROUND: Serologic measurement of antibodies to Epstein-Barr virus (EBV)

immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been
used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was
found that plasma EBV DNA concentration is an indicator for the staging and prognosis
of patients with NPC. To determine whether there is a correlation between plasma EBV
DNA levels and serum levels of IgA/VCA, the authors measured both in patients with
NPC and in a control group. METHODS: Real-time polymerase chain reaction was used
for quantitative analysis of plasma EBV DNA concentration, and enzyme-linked
immunoadsorbent assay was used to measure EBV VCA/IgA in patients with primary
NPC (n = 120 patients), locally recurrent NPC (n = 8 patients), and distant metastatic
NPC (n = 21 patients) among 76 patients with NPC after the completion of radiotherapy,
in 60 patients with NPC in clinical remission, in 38 patients with non-NPC tumors, and in
47 control individuals. RESULTS: The median plasma EBV DNA levels were 6200
copies/mL, 9200 copies/mL, and 2050 copies/mL in patients with primary, locally
recurrent, and distant metastatic NPC, respectively, but declined to 0 copies/mL in
patients with clinically remissive NPC, in patients who completed radiotherapy, in
patients with non-NPC tumors, and in the control group. In contrast, EBV VCA/IgA titers
and detection rates remained high in all NPC groups. Plasma EBV DNA levels were
significantly higher in patients who had serum VCA/IgA titers > or = 1:640 (median,
83,450 copies/mL) compared with the levels in patients who had titers < or = 1:320
(median, 17,200 copies/mL). Patients with NPC who had advanced TNM stage (Stages
III and IV; median, 8530 copies/mL) and T classification (T3 and T4 tumors; median,
8530 copies/mL) had significantly higher plasma EBV DNA levels compared with
patients who had early TNM stage (Stages I and II; median, 930 copies/mL) and T
classification (T1 and T2 tumors; median, 3700 copies). Patients who had advanced TNM
stage NPC had significantly higher mean VCA/IgA titers (1:424) compared with patients
who had early TNM stage NPC (1:246), but there was no correlation between IgA/VCA
titer and T or N classification of NPC. CONCLUSIONS: The results suggest that plasma
EBV DNA detection is a more sensitive and specific marker than the serum IgA/VCA
titer for the diagnosis and monitoring of patients with NPC. These findings provide
convincing evidence for the use of plasma EBV DNA measurements for the early
diagnosis and staging of NPC as well as for monitoring recurrence and metastasis of this
tumor. Copyright 2004 American Cancer Society.
Significance of plasma IgA and IgG antibodies to
Epstein-Barr virus early and viral capsid antigens in
Thai nasopharyngeal carcinoma.
Tiwawech D, Srivatanakul P, Karaluk A, Ishida T.

Research Division, National Cancer Institute, Bangkok, Thailand. tdanai@hotmail.com

Epstein-Barr virus (EBV) is an important causal factor of human nasopharyngeal

carcinoma (NPC). High levels of serum IgA and IgG antibodies to EBV early and viral
capsid antigens (IgA/EA, IgA/VCA, IgG/EA and IgG/VCA) have been reported in NPC
patients. Since specific serum IgA/EA, IgA/VCA and IgG/EA are claimed to be useful
serological markers for NPC. In order to evaluate whether plasma IgA/EA, IgA/VCA,
IgG/EA and IgG/VCA antibody levels are useful markers for diagnosis and prognosis of
Thai NPC, we examined the prevalence of these antibodies in 79 NPC patients, and 127
age-matched controls (47 healthy subjects (HS), 32 cases of other disease (OD) and 48
cases of other cancer (OC)) by using an indirect immunofluorescence assay. The
prevalence of plasma IgA/EA, IgA/VCA, and IgG/EA in NPC patients (55.7, 68.4 and
68.4%) was significantly higher than in the HS (0.0, 0.0 and 20.5%,), OD (0.0, 0.0 and
3.1%) and OC (0.0, 0.0 and 20.8%) groups (p<0.05). The prevalence of plasma IgG/VCA
in NPC patients (93.7%) was significantly different from those for the OD and OC
groups (71.9 and 43.8%) but not for the HS group (89.4%). In NPC patients, the
geometric mean titers (GMT) of plasma IgA/EA, IgA/VCA and IgG/EA were increased
with an advanced clinical stage of disease but not IgG/VCA. In contrast, GMT of
IgG/VCA was increased with aggressive type of disease (histological type) but not
IgA/EA, IgA/VCA, and IgG/VCA. The results of our study suggest that plasma IgA/EA,
IgA/VCA and IgG/EA antibodies may be useful markers for diagnosis and assessing
prognosis of Thai NPC

Functional inactivation of EBV-specific T-lymphocytes

in nasopharyngeal carcinoma: implications for
tumor immunotherapy.
Li J, Zeng XH, Mo HY, Rolén U, Gao YF, Zhang XS, Chen QY, Zhang L, Zeng MS,
Li MZ, Huang WL, Wang XN, Zeng YX, Masucci MG.

State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen
University, Guangzhou, China.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignancy

with high prevalence in Southern Chinese. In order to assess whether defects of EBV-
specific immunity may contribute to the tumor, the phenotype and function of circulating
T-cells and tumor infiltrating lymphocytes (TILs) were investigated in untreated NPC
patients. Circulating naïve CD3+CD45RA+ and CD4+CD25- cells were decreased, while
activated CD4+CD25+ T-cells and CD3-CD16+ NK-cells were increased in patients
compared to healthy donors. The frequency of T-cells recognizing seven HLA-A2
restricted epitopes in LMP1 and LMP2 was lower in the patients and remained low after
stimulation with autologous EBV-carrying cells. TILs expanded in low doses of IL-2
exhibited an increase of CD3+CD4+, CD3+CD45RO+ and CD4+CD25+ cells and 2 to 5
fold higher frequency of LMP1 and LMP2 tetramer positive cells compared to peripheral
blood. EBV-specific cytotoxicity could be reactivated from the blood of most patients,
whereas the TILs lacked cytotoxic activity and failed to produce IFNgamma upon
specific stimulation. Thus, EBV-specific rejection responses appear to be functionally
inactivated at the tumor site in NPC.