Detection of antibodies against virally-induced tumor-associated antigens by mixed hemadsorption

Antigens were solubilized and attached to glass slides. The coated glass slides were then used to detect relevant antibodies by a mixed hemadsorption technique. These studies focused primarily on solubilizing the Epstein-Barr virus-associated antigens VCA, EA and MA. Well-characterized, discordant sera from patients with Burkitt's lymphoma and nasopharyngeal carcinoma were then used to evaluate the antigenicity of slides coated with the solubilized antigenic extracts. Good correlations were observed between titers of these sera for VCA, EA and MA as determined by immunofluorescence methods and by mixed hemadsorption. Most antigenic extracts could be stored directly or as coated-glass slides for many months with only moderate decreases in antigenicity. Antibodies to Epstein-Barr-associated nuclear antigen (EBNA) were not detectable in these studies.     

Early primary infection and high Epstein-barr virus antibody titers in greenland eskimos at high risk for nasopharyngeal carcinoma

In a comparative study of populations at high and low risk of nasopharyngeal carcinoma (NPC), sera from 442 Eskimo and 770 Danish children and adolescents were tested for the presence of antibodies against Epstein-Barr virus (EBV). Eskimo children in Greenland were seropositive at an early age and showed significantly higher titers of IgG antibody to the viral capsid antigen (VCA) (p<0.0001) and soluble (S) antigen (p<.005) than Danes matched for age and sex, but had similar levels of IgA antibody to VCA and IgG antibody to the early antigen (EA). The high geometric mean VCA (IgG) titers found in certain age groups of Eskimo children were as high as those previously reported from areas in Africa highly endemic for Burkitt's lymphoma. In Greenland, neither location nor household size was a determining factor for prevalence or titer of VCA (IgG). The high antibody titers among Eskimo children probably reflect exposure to a large inoculum of EBV at the time of primary infection, infection early in life and/or re-exposure due to the higher incidence of EBV infection in Greenland. In view of the high incidence of NPC in Greenland and the known association of this tumor with EBV, we speculate that the time and quantitative aspects of the primary infection are also factors of relevance in the etiology of NPC.     

Significance of Plasma IgA and IgG Antibodies to Epstein-Barr Virus Early and Viral Capsid Antigens in Thai Nasopharyngeal Carcinoma

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. ‍     

Epstein-Barr virus (EBV)-associated antibody patterns in malignant lymphoma and leukemia. II. Chronic lymphocytic leukemia and lymphocytic lymphoma

Sera from Swedish patients with chronic lymphocytic leukemia (CLL) and lymphocytic lymphona (LL) were titrated for antibodies to viral capsid antigens (VCA) of the Epstein-Barr virus (EBV) by the indirect immunofluorescence technique and to EBV-determined cell membrane antigens by blocking of direct cell membrane immunofluorescence (BI). Previously tested sera from healthy Swedish donors served as controls. While 40% of the sera from CLL patients showed relatively high serological reactivities, the mean anti-VCA and BI values did not differ significantly from the control group. The LL group of sera showed significantly higher reactivities than the controls. The most highly reactive sera were found in patients with poorly differentiated LL at frequencies and with mean values approaching those seen in Burkitt's lymphoma, nasopharyngeal carcinoma and Hodgkin's sarcoma.     

Comparative studies on immunity to EBV-associated antigens in NPC patients in North America, Tunisia, France and Hong Kong.

This study compared the relative antibody titers to EBV-related antigens in patients with nasopharyngeal carcinoma (NPC) and controls from a high-incidence (Hong Kong), an intermediate incidence (Tunisia), and two low-incidence (France, North America) areas to determine which of several EBV antibodies best differentiated NPC patients from controls. Antibodies measured include anti-virus capsid antigen (VCA), anti-early antigen (EA), anti-soluble antigen by complement-fixation (CF) and antibody-dependent lymphocyte cytotoxicity (ADLC). A matched pair analysis showed that significantly more NPC patients had higher VCA and EA but not CF or ADLC antibody titers than their matched cancer controls. The comparison of geometric mean titers between NPC cases and controls was more than seven-fold (816 vs 11.5) for EA antibody and more than three-fold (359.7 vs 95.4) for VCA anti-body (p less than 0.01). A two-fold difference was seen for CF antibody to soluble antigens (27.3 vs 12.9, p less than 0.01) and a three-fold difference (2657.7 vs 870.9, p less than 0.05) was observed for ADLC. Our finding of significant differences between NPC patients from four countries and their matched controls suggest that if EBV is the etiological agent of NPC in Chinese, it is quite likely to cause the majority of NPC cases in other ethnic groups living in other countries as well.     

Neutralizing EBV-specific IgA in throat washings of nasopharyngeal carcinoma (NPC) patients.

Throat washings from 26 nasopharyngeal carcinoma (NPC) patients from Hong Kong and Tunisia were studied for the presence of transforming EBV. Only six (23%) were found positive which led to the hypothesis of a neutralizing factor in such salivas. The search for EBV-specific antibodies showed that NPC saliva contained neutralizing VCA and EA IgA (54 and 27% respectively) and VCA and EA IgG (73 AND 54% respectively). Both transforming and non-transforming throat washings contained virus particles as visualized by electron microscopy, but in non-transforming salivas (containing IgA and IgG) the particles were found to be clumped. Comparative study of throat washings from patients with Burkitt's lymphoma (BL); infectious mononucleosis (IM), immunodeficiencies, other cancers, and healthy subjects showed that IgA were restricted to NPC cases.     

Significance of cell-free epstein-barr virus DNA in monitoring prognosis of nasopharyngeal carcinoma

Objective It has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/lgA and EA/lgA levels. Methods E8V -DNA, VCA/lgA, and EA/lgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/lgA and EA/lgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma. Results The median plasma EBV-DNA concentration was 135,100 copies/ ml (interquartile range: 5,525-1,003 750) in metastatic group, 20,500 copies/ ml (interquartile range: 0 -58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P< 0.05). The levels of VCA/lgA and EA/lgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV -DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) after the radiation was finished (P< 0.05). However, the levels of VCA/lgA and EA/lgA showed no significant difference. Conclusion Determination of plasma cell -free EBV -DNA level is more valuable than evaluation of VCA/lgA and EA/lgA for monitoring the prognosis of NPC patients.     

血浆 EB病毒游离 DNA检测对监测鼻咽癌患者预后的意义

背景与目的:有报道 , 测定血浆中的 EB病毒游离 DNA( EBV-DNA)的拷贝数可作为诊断及监测鼻咽癌患者病情变化的手段之一.本研究旨在评价血浆 EBV-DNA检测在鼻咽癌患者预后监测上的价值, 并进一步与 VCA/IgA、 EA/IgA进行比较.方法:比较鼻咽癌放疗后 30例远处转移患者、 22例局部复发患者、 24例无 瘤生存者血浆中 EBV-DNA、 VCA/IgA、 EA/IgA水平.分别应用荧光定量 PCR方法检测血浆 EBV-DNA水平,免疫酶法检测 VCA/IgA、 EA/IgA;前瞻性观察 20例初诊鼻咽癌患者放疗前、放疗剂量达 40 Gy时及放疗结束时上述指标的变化. 结果:放疗后各组不同预后患者的血浆 EBV-DNA含量的中位数有显著性差异, 远处转移组为 135 100 copies/ml(四分线区域 5 525～ 1 003 750 copies/ml) >局部复发组的 20 500(四分线区域 0～ 58 500 copies/ml) > 无瘤生存组的 0 copy/ml(四分线区域 0～ 0 copy/ml), P均 < 0.05. 远处转移组的血浆 EBV-DNA水平高者较多, 当阳性标准为 1 000 000 copies/ml时,诊断远处转移组的敏感性为 27.3%,而诊断局部复发组的敏感性为 0.0%,特异性均为 100.0%.在初诊患者放疗前、放疗剂量达 40 Gy时及放疗结束时, EBV-DNA水平逐渐降低,平均含量分别为 32 050 copies/ml(四分线区域 3 880～ 317 750 copies/ml)、 0 copy/ml(四分线区域 0～ 14 375 copies/ml)、 0 copy/ml(四分线区域 0～ 2 940 copies/ml), P均 < 0.05, 而 VCA/IgA、 EA/IgA的水平未见明显变化. 结论: 血浆 EBV-DNA检测可用于监测鼻咽癌患者预后,其价值明显优于 VCA/IgA、 EA/IgA.     

Evolution of complement-fixing antibody titers with the development of Burkitt's lymphoma

Sera of 29 patients with Burkitt's lymphoma (BL) were studied at different stages of the disease process for complement-fixing (CF) activities against a soluble antigen extracted from a leukaemia-derived and virus-producing lymphoblastoid line (QIMR-WIL line of Pope). The CF antibody activity was low (with a geometric mean titre (GMT) of 12.35) in sera from patients with controlled tumour, and high (GMT of 38) in patients with advanced or progressive tumours. Furthermore, in seven cases, the CF litres decreased with the regression of the tumour, and in five cases, the CF titres increased in parallel with the progression of the disease. This situation recalls that observed in acute viral infections, where CF antibodies disappear rapidly once the infection is controlled. CF and EA (early antigen (s)) antibodies should be studied in parallel on the same sera as a possible means for establishing prognosis in BL patients.     

2007～2008年广西苍梧县石桥镇鼻咽癌普查结果初步分析*

目的:通过鼻咽癌普查了解广西苍梧县高发区鼻咽癌流行状况,探讨可持续发展的鼻咽癌早诊早治普查模式。方法:于2007年6 月～2008年12月在广西苍梧县石桥镇鼻咽癌现场进行鼻咽癌普查。在鼻咽癌现场建立人口档案;进行流行病学调查;参加普查者均进行头颈部检查及间接鼻咽镜检查,鼻咽癌EB病毒壳抗原IgA 抗体（IgA/VCA ）和早期抗原IgA 抗体（IgA/EA）血清学检测;检查结果可疑和血清学结果阳性者均进行鼻内镜检查;鼻咽部可疑病变者行活组织病理检查;鼻咽癌普查结果均输入电脑,应用EpiData3.1 建立数据库。结果:鼻咽癌现场筛查人群8 458 人,其中EB病毒IgA/VCA 阳性522 例,EB病毒IgA/EA阳性28例,进行鼻内镜检查410 例,鼻咽部活组织检查45例,检出鼻咽癌12例,其中早期鼻咽癌6 例,接受治疗11例。鼻咽癌人群检出率141.87/10 5,早诊率50% ,治疗率91.6% 。结论:广西苍梧县鼻咽癌早诊早治普查方案是鼻咽癌防治的重要策略之一,而鼻咽癌早诊早治普查工作应持续发展。      

Significance of Cell-Free Epstein-Barr Virus DNA in Monitoring Prognosis of Nasopharyngeal Carcinoma

Objective  It has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/lgA and EA/lgA levels. Methods  E8V -DNA, VCA/lgA, and EA/lgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/lgA and EA/lgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma. Results  The median plasma EBV-DNA concentration was 135,100 copies/ ml (interquartile range: 5,525-1,003 750) in metastatic group, 20,500 copies/ ml (interquartile range: 0 -58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P< 0.05). The levels of VCA/lgA and EA/lgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV -DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) after the radiation was finished (P< 0.05). However, the levels of VCA/lgA and EA/lgA showed no significant difference. Conclusion  Determination of plasma cell -free EBV -DNA level is more valuable than evaluation of VCA/lgA and EA/lgA for monitoring the prognosis of NPC patients.     

Primary Epstein-Barr virus infections in African infants. I. Decline of maternal antibodies and time of infection.

Thirty-one infants living in Accra, Ghana, an area endemic for Burkitt's lymphoma, were visited at monthly intervals for the first 15 months of life and once again at 21 months. Sera obtained at each visit were tested for antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA), EBV-induced early antigens (EA) and EBV-associated nuclear antigen (EBNA) by immunofluorescence techniques as well as for EBV-neutralizing antibodies and antibody-dependent cell-mediated cytolysis. All infants had maternal antibodies to VCA at 1 month of age and the majority also antibodies detected by the other tests, except anti-EA. The maternal anti-VCA titers declined in subsequent months according to a half-life of nearly 5 weeks. Depending on the initial titers, all infants became seronegative for all antibodies by 2–8 months of age, with anti-VCA persisting longest. The earliest primary EBV infection occurred in the third month after maternal antibodies to VCA had become non-detectable. By 12 months of age, 44% of the infants had seroconverted, by 15 months, 62% and by 21 months, 81%. There was no seasonal variation in the incidence of infections. Infants from families of the lowest socio-economic level tended to become infected somewhat earlier than those from better situated families (p = 0.22) but no other factors, such as household size or crowding, seemed to be associated with enhanced risk of early infection.     

A prospective study of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in adults with human immunodeficiency virus-1

Antibody titres against Kaposi's sarcoma associated herpesvirus (KSHV or human herpesvirus 8 (HHV-8)) and Epstein-Barr virus (EBV) were examined in people who subsequently developed Kaposi's sarcoma and non-Hodgkin's lymphoma, within randomised controlled trials of antiretroviral therapy in adults infected with the human immunodeficiency virus-1 (HIV). For each case of Kaposi's sarcoma (n=189) and each case of non-Hodgkin's lymphoma (n=67), which developed after randomisation, one control was randomly selected from other trial participants, after matching for age, sex, ethnicity, mode of HIV transmission, type of treatment received and period of follow-up. Using sera taken an average of two and a half years before the diagnosis of cancer, titres of antibodies against KSHV latent (LANA) and lytic (K8.1) antigens and against EBV (VCA) antigens were investigated in relation to subsequent risks of cancer by calculating odds ratios (OR) using conditional logistic regression. Latent antibodies against KSHV were detectable among 38% (72 out of 189) of Kaposi's sarcoma cases and 12% (23 out of 189) of their controls (OR=4.4, 95% confidence intervals (CI) 2.3-8.3, P<0.001). The OR for Kaposi's sarcoma increased with increasing antilatent KSHV antibody titre (chi(2)(1) for trend=32.2, P<0.001). Lytic antibodies against KSHV were detectable among 33% (61 out of 187) of Kaposi's sarcoma cases and 19% (36 out of 187) of their controls (OR=2.0, 95% CI 1.2-3.4, P=0.003) and the OR for Kaposi's sarcoma increased with increasing antilytic KSHV antibody titre (chi(2)(1) for trend=6.2, P=0.02). Virtually, all cases and controls had anti-EBV antibodies detected and the OR for non-Hodgkin's lymphoma associated with a doubling of the anti-EBV antibody titre was estimated to increase by a multiplicative factor of 1.3 (95% CI 0.9-1.7, P=0.1). Kaposi's sarcoma was not associated with antibody levels against EBV (P=0.4) and non-Hodgkin's lymphoma was not associated with antibodies against KSHV (latent P=0.3; lytic P=0.5). Adjustment for CD4 count at the time of sample collection made no material difference to any of the results. In conclusion, among human immunodeficiency virus infected people, high levels of antibodies against KSHV latent and lytic antigens are strongly associated with subsequent risk of Kaposi's sarcoma but not non-Hodgkin's lymphoma. Antibody titre to EBV does not appear to be strongly associated with subsequent risk of Kaposi's sarcoma or non-Hodgkin's lymphoma in HIV infected people.     

Nasopharyngeal carcinoma. IV. Evolution of complement-fixing antibodies during the course of the disease

Sequential sera from 37 patients with nasopharyngeal carcinoma (NPC), with either controlled or uncontrolled tumours after radiotherapy, were studied for complement-fixing (CF) antibodies against a soluble antigen extracted from the QIMR-WIL lymphoblastoid line. When compared with results obtained previously with the same antigen on sequential Burkitt's lymphoma (BL) sera, the NPC sera exhibited (1) approximately ten-fold higher CF antibody titres than the BL sera; (2) an overall stability of CF titres in the uncontrolled tumour groups contrasting with the situation in BL; (3) a two- to four-fold decrease in CF titres in the controlled tumour groups; (4) similar CF titres in patients at stage I or IV of the disease. The above suggests an active and long-standing EBV infection before and during the development of the clinical NPC disease.     

Nasopharyngeal carcinoma. IX. Antibodies to EBNA and correlation with response to other ebv antigens in chinese patients.

Ninety-five sera from Chinese NPC patients in different stages of the disease, 38 sera from Chinese patients with other cancers, and 50 normal Chinese sera, were titrated for EBNA, VCA, EA and complement-fixing (CF/S) EBV-specific antibodies. The geometric mean (GMT) EBNA antibody titre of patients with NPC at stage I was found to be four times higher than that of normal individuals and increased in parallel with clinical deterioration. Antibody titres against EBNA did not correlate with either VCA or EA antibodies but, in general, correlated with CF/S antibodies. EA antibodies correlated relatively well with VCA antibodies and discriminated better than EBNA titre between NPC at stage I and controls.     

EB virus-associated antibodies in Caucasian patients with carcinoma of the nasopharynx and in long-term survivors after treatment

Sera from 30 Swedish patients with nasopharyngeal carcinoma (NPC) collected before or shortly after commencement of therapy and from 24 long-term survivors (LTS) were tested for antibodies to Epstein-Barr virus (EBV) capsid antigens (VCA), to the O and R components of the EBV-induced early antigen (EA) complex, and to EBV-determined cell membrane antigens (MA). In the tumor-bearing patients, all serologic reactivities increased overall from stage I to later stages of the disease: that is, with an increase in total tumor burden. In the LTS, who had remained apparently tumor-free for 3 to 29 years, all reactivities were substantially lower than in the tumor-bearing patients. While the data agreed in principle with those reported previously for Chinese NPC patients, there were considerable differences with respect to the incidence and titres of antibodies to the D component which, as discussed, might reflect a reduced responsiveness of Caucasian NPC patients or a difference in the distribution of various types of the disease among ethnic groups.     

Increased incidence of IgA antibodies to the Epstein-Barr virus-associated viral capsid antigen and early antigens in patients with chronic lymphocytic leukemia

Antibody titers to Epstein-Barr virus (EBV)-associated early antigens (EA) and the viral capsid antigen (VCA) were determined by ELISA on 263 sera obtained from healthy donors, patients with Hodgkin's disease (HD), non-Hodgkin lymphomas (NHL), infectious mononucleosis (IM), Burkitt's lymphoma (BL), and nasopharyngeal carcinoma (NPC). As expected, most lymphoma patients showed markedly elevated anti-VCA IgG and anti-EA IgG antibody titers. Only one patient in the NHL group (n = 56) consisting of patients with lymphomas other than chronic lymphocytic leukemia (CLL) and hairy-cell leukemia (HCL), and 3 patients with HCL (n = 19) had high antibody titers of the IgA class to VCA and EA. Seventeen out of 48 patients (36%) with CLL had high IgA anti-VCA titers and 10 of these sera (21%) also contained IgA anti-EA. The geometric mean titer (GMT) of IgA anti-VCA was 2,510, the GMT of IgA anti-EA was 780. These antibody titers were about 10 times lower than the corresponding GMT of the NPC patients investigated in this study. The elevated IgG and IgA antibody titers to VCA and EA in CLL and HCL patients seem to reflect an immunodeficiency secondary to the malignant disease leading to reactivation of latent EBV infection. The possibility that at least some of these B-cell lymphomas are associated with EBV cannot be excluded.     

鼻咽癌患者发病前后EB病毒VCA/IgA和EA/IgA滴度动态分析

目的 观察鼻咽癌患者发病前后EB病毒VCA/IgA、EA／IgA滴度的变化规律,及其在鼻咽癌筛查中的作用。方法 收集中山市首次鼻咽癌筛查后12年VCA／IgA阳性人群中54例新发鼻咽癌患者发病前后的血清学资料,用免疫酶法检测EB病毒抗体VCA/IgA和EA／IgA。结果 确诊前1～7年VCA／IgA、EA／IgA总体呈上升趋势。发病前7～4年,VCA／IgA平均滴度在1：21．04上下波动,确诊前第3年起VCA／IgA急剧上升,确诊时几何平均滴度接近1：80,EA／IgA高较为缓慢,确诊时几何平均滴度为1：6．49。放疗后两种滴度均呈快速下降趋势,第4年起接近阳性人群的平均滴度。结论 多数鼻咽癌患者在确诊前3年,VCA／IgA滴度持续增高,但EA／IgA滴度增高缓慢;VCA／IgA可以检出早期鼻咽癌,但EA／IgA作用不大;鼻咽癌发展临床前期平均时间为3年。     

Frequent association of Epstein-Barr virus in Japanese patients with Burkitt's lymphoma.

Seven Japanese patients with Burkitt's lymphoma (BL), residing in Hokkaido, were studied during the period, 1979-1991. Immunological analyses of their lymphoma cells showed all to express surface and/or cytoplasmic immunoglobulins. Chromosomal analysis was performed in five cases. Four of the five lymphomas had the chromosomal translocation, t(8;14), and one had t(2;8). Three patients had extremely high IgG antibody titers to Epstein-Barr virus (EBV) viral capsid antigen (VCA) and to EBV early antigens (EA). Two patients had positive antibodies to EA, and two others had normal antibody patterns comparable to those of EBV-seropositive age- and sex-matched healthy controls. Four of the seven lymphomas (57.1%) were positive for EBV-determined nuclear antigen (EBNA) by anticomplement immunofluorescence and/or EBV DNA using DNA-DNA reassociation kinetics, and/or Southern blot analysis. The frequency of EBV positivity in BL patients residing in Hokkaido was higher than that of cases previously reported in Japan. Three of the four EBV genome-positive BL patients responded well to chemotherapy, radiotherapy and/or surgical treatment, with no significant relapse being observed during the study period. In contrast, EBV genome-negative patients had poor prognoses despite having similar levels of clinical staging at the time of diagnosis.     

Presence of EBNA in nasopharyngeal carcinoma and control patient tissues related to EBV serology.

A search was made for Epstein-BARR virus (EBV) associated nuclear antigen (EBNA) in touch preparations of fresh biopsy material from 26 carcinomas of the nasopharynx, 39 other tumours of the head and neck, the nasopharyngeal mucosa of 32 patients in whom nasopharyngeal neoplasm had been excluded, and the mucosa from enlarged but non-neoplastic tonsils removed from 12 patients. EBNA-positive cells were uniformly detected in the preparations from the undifferentiated and poorly differentiated squamous-cell carcinomas of the nasopharynx, provided they contained tumour-cell aggregates. Such cells were not detected in the preparations from the single case of well-differentiated papillary adenocarcinoma in the nasopharyngeal carcinoma group. There were no moderately or well-differentiated squamous-cell carcinomas among the nasopharyngeal carcinoma group. Among other tumours of the head and neck, only three undifferentiated carcinomas of the nasal fossa were found to contain EBNA-positive cells. None of the nasopharyngeal or tonsillar mucosal preparations contained such cells. These findings confirm the unique regular association of EBNA with nasopharyngeal carcinoma of undifferentiated and poorly differentiated squamous-cell types (NPC). The EBV-related serological findings support the value of tests for IgG and IgA antibodies to VCA and EA(D) in the exclusion of NPC in patients with suspicious symptoms and the differentiation between NPC and other tumours of the head and neck. Examination of biopsy specimens for the presence of EBNA-positive cells or EBV-DNA is essential, however, for confirmation of the diagnosis.