The seroepidemiology of infection due to Epstein-Barr virus in southern India

We investigated the seroepidemiology of infection due to Epstein-Barr virus (EBV) in 181 south Indian subjects aged 0-25 years using the indirect immunofluorescence method to titrate antibodies to viral capsid antigen (VCA), nuclear antigen (EBNA), and early antigen (EA). The age-specific prevalence of IgG antibodies to VCA rose rapidly to 90% by the age of 5 years. The prevalence of VCA-specific IgM and the geometric mean titre of VCA-specific IgG antibodies were highest between the ages of 6 months and 2 years, the median age of primary infection being 1.4 years. Thus primary EBV infection occurs early in life. EA antibody prevalence was highest (55%) in the third year of life and remained between 30% and 40% thereafter. This pattern of EA antibody prevalence suggests that the latent EBV infection that persists lifelong after primary infection may be reactivated in many individuals. EBNA antibody prevalence was low until the age of 2 years but rose to 80% in the fourth year. Geometric mean titres of antibodies to EA and EBNA were low and stable at all ages. These results are similar to data from areas where EBV-associated Burkitt's lymphoma is endemic and indicate a high EBV infection load early in life.     

Humoral immune response in Epstein-Barr virus infections. I. Elevated serum concentration of the IgG1 subclass in infectious mononucleosis and nasopharyngeal carcinoma

Using radial immunodiffusion we measured IgG subclass concentrations and studied their distribution in serum samples from patients with infectious mononucleosis (IM) and nasopharyngeal carcinoma (NPC), two Epstein-Barr virus (EBV)-associated diseases, in comparison with two control groups [completely anti-EBV negative persons and subjects carrying antibodies to the viral capsid antigen (VCA)]. Antibody titres to VCA and to the early antigen (EA) were determined by indirect immunofluorescence and revealed characteristic patterns for the respective diagnostic groups. Nephelometric assays served for quantitating total protein, albumin, total IgG, IgA and IgM in all the sera. In the IM and NPC groups the concentration of IgG1 was significantly elevated by more than 50% whereas the other three subclasses remained unchanged as compared with the controls. Correspondingly, we found a significant increase of total IgG in IM and NPC. In IM, the only disease where VCA-specific IgM antibodies have been reported to occur, IgM levels were markedly elevated. Our data suggest that the IgG1 subclass plays an important role in the humoral immune response to EBV-determined antigens and that it is possibly involved in the control of virus infection.     

Heterogeneity of immune defects in three children with a chronic active Epstein-Barr virus infection

Three children, all girls, showed long-lasting clinical and serologic evidence of chronic active Epstein-Barr virus (EBV) infection. Extremely high serum titers of IgG- and IgA-type VCA antibodies and EA antibodies were present, whereas EBNA antibody titers were in the range of those found in seropositive individuals. All three patients repeatedly showed the presence of nonspecific pokeweed mitogen (PWM)-activatable suppressor cells in the peripheral blood. The analysis of EBV-specific cytotoxic T cells showed that one patient exhibited normal cytotoxicity, whereas a second patient demonstrated no EBV-specific cytotoxicity together with unusually high levels of virus-infected B cells in the blood and lymph node. The third patient repeatedly showed refractoriness of the circulating B cells to EBV infection, probably on the basis of some developmental defect. It was concluded that each patient has his or her own peculiar defect in the virus-host balance, indicating that heterogeneity may underlie the syndrome of chronic active EBV infection in humans.     

Reactivation of Epstein-Barr virus during early infection with human immunodeficiency virus.

Reactivation of Epstein-Barr virus (EBV) in early human immunodeficiency virus (HIV) infection was investigated in 49 homosexual men who seroconverted to HIV (cases) as compared with 49 matched controls who remained seronegative to HIV during a longitudinal study. EBV infection was reactivated in cases 6 months, but not 12 months, prior to HIV seroconversion as compared with controls and remained reactivated during 18 months of follow-up after HIV seroconversion, as shown by increases in immunoglobulin (Ig) G antibody titers to EBV early antigen. Antibody titers to EBV viral capsid antigen did not differ between cases and controls prior to the time of seroconversion to HIV but were significantly increased among cases by the first seropositive study visit and remained elevated during the 18 months after HIV seroconversion. Total serum IgG levels were increased in cases at the visit of seroconversion, and during 18 months of follow-up, but did not correlate with enhanced IgG production specific for EBV antigens. Significant decreases in numbers of CD4+ cells and increases in numbers of CD8+ cells during this early phase of HIV infection were not associated with changes in patterns of EBV antibody responses. Reactivation of EBV beginning 6 months before HIV seroconversion may have implications regarding the role of this herpesvirus in the pathogenesis of HIV.     

Serological and virological investigation of the role of the herpesviruses EBV,CMV and HHV‐6 in post‐infective fatigue syndrome

Multiple previous studies have sought evidence for ongoing, active infection with, or reactivation of, Herpesviruses in patients with chronic fatigue syndrome (CFS), with conflicting results. This study aimed to clarify this by studying 20 patients enrolled in a well‐characterized model of the onset and evolution of CFS, the prospective cohort of the Dubbo Infection Outcomes Study (DIOS). The patients selected for examination included five CFS patients with primary Epstein–Barr virus (EBV) infection; five CFS patients with acute viral infection not caused by EBV; and 10 matched controls with prompt resolution of primary EBV infection. Serum samples from three timepoints were assayed using a comprehensive range of serological assays for EBV, HHV‐6, and CMV. Viral genomes were assessed using quantitative PCR assays. All patients were seropositive for HHV‐6, and 10 were seropositive for CMV at infection baseline (five patients and five controls). Low titer CMV IgM antibodies were found at infection baseline in two of these cases and three control patients. HHV‐6 IgG antibody titers were highest at infection baseline but did not differ between the CFS cases and the control patients. There were increases in EBV IgG VCA p18, EBNA‐1 IgG, and EA IgG titers over time, but these did not differ between CFS cases and control patients. EBV and HHV6 DNA levels were at control levels in a minority of samples, and CMV was undetectable in all samples. These data do not support the hypothesis of ongoing or reactivated EBV, HHV‐6, or CMV infection in the pathogenesis of CFS. J. Med. Virol. 82:1684–1688, 2010. 2010 Wiley‐Liss, Inc.     

北京地区儿童EB病毒感染的血清学调查

目的 了解北京地区儿童EB病毒感染现状.方法 选取北京地区0～14岁儿童的血清589份,应用微润赛润ELISA classic EBV VCA IgG试剂盒,在波长405 nm下检测血清样品的吸光度值.参照试剂盒内专用的标准曲线和临界值判定血清样品EB病毒感染与否.根据专用公式计算EBV VCA IgG抗体活性.利用统计学软件SPSS 13.0分析比较北京城区和农村儿童EBV感染阳性百分率及EBV VCA IgG抗体强度.结果 血清学检测显示北京地区0～14岁儿童EBV感染阳性率为83.6%,其中城市为80.8%,农村为86.2%.EBV感染高峰集中在3岁之前为71%,其中城市为67.7%低于农村75.3%,6岁之前为82.5%.统计学分析比较城市和农村儿童不同年龄的EBV感染阳性百分率和EBV VCA IgG抗体活性具有显著差异.结论 北京城区儿童6岁之前EBV感染阳性百分率有所降低,部分儿童初次感染年龄向后推移.     

Epstein-Barr Virus in Normal Pregnant Women*

ABSTRACT: Acquired immune suppression accompanying normal pregnancy may be associated with reactivation of Epstein-Barr virus (EBV). Pregnant women with reactivated EBV having anti-EA antibodies show high titers of antiviral capsid antigen (VCA) geometric mean titers (GMT) of 522 versus 170 in those lacking anti-early antigen (EA). Among twenty-seven seropositive women at parturition, 17 (63%) had generated antibody to EA, and all 27 (100%) demonstrated significant increases in antibody to VCA (p < 0.01). In contrast, antibody titers to cytomegalovirus, herpes hominis, varicella-zoster, and rubella viruses in the pregnant women were comparable to those found in nonpregnant controls.     

Positive correlation between Epstein-Barr virus viral load and anti-viral capsid immunoglobulin G titers determined for Hodgkin's lymphoma patients and their relatives

Markers of Epstein-Barr virus (EBV) infection include measures of specific serological titers and of viral load (VLo) in peripheral blood mononuclear cells. Few studies have investigated the correlation between these two phenotypes. Here, we found that there was no correlation between VLo and either anti-EBV nuclear antigen type 1 or anti-early antigen immunoglobulin G (IgG) titer but that anti-viral capsid antigen (VCA) IgG titer increased with VLo in peripheral blood mononuclear cells in patients with Hodgkin's lymphoma (P = 3.10(-3)). A similar pattern was observed in healthy first-degree relatives (parents and siblings) of patients (P = 6.10(-4)). Our results indicate that anti-VCA IgG titers and EBV VLo are specifically correlated EBV phenotypes.     

Effect of primary Epstein-Barr virus infection on human herpesvirus 6, cytomegalovirus, and measles virus immunoglobulin G titers.

Immunoglobulin G antibody titers to human herpesvirus 6 (HHV-6), measles virus, and cytomegalovirus (CMV) were examined in serum samples from 31 patients with Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM). Sera were drawn sequentially from the same patients less than or equal to 7 days until 3 years after onset of IM. In seropositive patients, there was a significant decrease with time after IM of the immunoglobulin G titers to the three viruses in the majority of patients; HHV-6 IgG titers decreased in 80%, measles virus IgG titers decreased in 75%, and CMV IgG titers decreased in 67%. Four patients contracted CMV infection during the observation period after IM. In these, HHV-6 IgG titers increased, while EBV and measles virus IgG titers remained essentially stationary. Polyclonal B-cell stimulation during IM is suggested to augment antiviral titers in general, but the increases of HHV-6 IgG titers during EBV and CMV infections may also be due to selective stimulation of memory B cells by related antigens or to reactivation of HHV-6 during infection with these herpesviruses.     

Activation of human herpesvirus-6 in children with acute measles.

Virological and serological studies were carried out prospectively to evaluate the possible activation of human herpesvirus-6 (HHV-6) in 50 infants and children with acute measles by isolation of HHV-6 from peripheral blood and by determining neutralizing antibodies to the virus. All but 5 patients (90%) were seropositive to HHV-6 in the acute stage of measles and 18 (40%) had a significant increase in HHV-6 antibody titers thereafter, whereas only 2 of 27 patients who were initially seropositive to Epstein-Barr virus (EBV) viral capsid antigen (VCA) had a significant rise in antibody titers to EBV VCA. Among 18 patients with a significant increase in HHV-6 titers, the virus was isolated from the peripheral blood mononuclear cells of three patients in the early convalescent stage of measles. These results indicate that activation of HHV-6 may occur frequently a few weeks after primary infection with the measles virus.     

High incidence of elevated antibody titers to Epstein-Barr virus in patients with uveitis

Summary. We assayed Epstein-Barr virus (EBV) antibody titers in patients’ sera using indirect immunofluorescence and tested for the presence of antibody to EBV immediate-early BZLF1 protein ZEBRA by Western blotting to explore the association of EBV infection with uveitis. IgG and IgA antibodies to viral capsid antigen (VCA), IgG antibodies to early antigen (EA), and antibodies to EBV nuclear antigen were detected at higher titers in sera of patients with uveitis than in the sera of healthy controls. Neither IgM antibody to VCA nor EA was detected in the patients’ sera. Anti-ZEBRA-IgG antibodies were detected in most patients’ sera, but not in those of healthy controls. These results suggest that uveitis might be a disease accompanied by EBV reactivation.     

Prevalence of primary versus reactivated Epstein-Barr virus infection in patients with VCA IgG-, VCA IgM- and EBNA-1-antibodies and suspected infectious mononucleosis.

BACKGROUND: In Epstein-Barr virus (EBV) infection, IgG- and IgM-antibodies to viral capsid antigen (VCA) and IgG-antibodies to Epstein-Barr nuclear antigen 1 (EBNA-1) can occur simultaneously both in late primary infection and during subclinical viral reactivation in immunocompetent persons, and the differential diagnosis is of importance. OBJECTIVES: To study the prevalence of primary infection and serological reactivation in patients with suspected primary EBV infection and with all three parameters present. STUDY DESIGN: Fifty serum samples from 43 consecutive patients referred for suspected infectious mononucleosis and positive for VCA IgG-, VCA IgM- and EBNA-1-antibodies by EIA, were tested for IgG-antibody avidity with an EBV IgG immunoblot. Sera were also tested for heterophile antibodies (HA). To verify the presence of IgM-antibodies an EBV IgM immunoblot was performed when high-avidity IgG-antibodies were found. RESULTS AND CONCLUSIONS: Of 43 patients with suspected primary EBV infection and VCA IgG-, VCA IgM- and EBNA-1-antibodies present, only 18 patients (42%) had a late primary infection. Twenty-one patients (49%) had high-avidity IgG-antibodies, indicating an IgM response due to reactivation, thus suggesting other causes for their symptoms. In 10 of these 21 patients the presence of IgM-antibodies was confirmed by immunoblot, indicating reactivation as a cause of IgM-antibodies in at least 23% of the 43 patients studied. Of 18 patients with primary infection, HA were detected in 16 (94%) of 17 patients tested. Only one (5%) of the patients with high-avidity antibodies had HA. Absence of HA in patients with this serological pattern is therefore a good indicator of reactivation, and conversely, the presence of HA is a good indicator of primary infection. In HA negative patients, avidity testing could be used for differential diagnosis.     

Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein–Barr virus IgG antibody titers

Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) IgG antibody titers. This study investigated whether antibody titers against HHV‐6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients. An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV‐6 IgG ≥1:320, EBV viral capsid antigen (VCA) IgG ≥1:640, and EBV early antigen (EA) IgG ≥1:160. Patients self‐rated physical and cognitive functioning as a percentage of their functioning prior to illness. Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning. Thirty‐two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively. Baseline antibody titers showed no significant association with response. After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001). Longer treatment was associated with improved response (P = 0.0002). No significant difference was found between responders and non‐responders among other variables analyzed. Valganciclovir treatment, independent of the baseline antibody titers, was associated with self‐rated improvement in physical and cognitive functioning for CFS patients who had positive HHV‐6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response. J. Med. Virol. 84:1967–1974, 2012. © 2012 Wiley Periodicals, Inc.     

Significance of specific Epstein-Barr virus IgA and elevated IgG antibodies to viral capsid antigens in nasopharyngeal carcinoma patients

The feasibility of using elevated Epstein-Barr virus (EBV) specific-IgG antiviral capsid antigen (VCA) and IgA anti-VCA antibody levels as an aid in diagnosis of nasopharyngeal carcinoma (NPC) was analyzed by determination of serum antibody titers to EBV in 54 NPC patients, 114 healthy blood donors, and 40 family members by the immunoperoxidase assay (IPA). No significant difference was found in the prevalence rate of EBV IgG anti-VCA antibodies (titer greater than or equal to 20) between the patient group and the control and family groups (100% vs 92% and 90%, respectively). The prevalence rate of elevated EBV IgG anti-VCA titers (greater than or equal to 80, greater than or equal to 160, greater than or equal to 320, greater than or equal to 640) was significantly higher in the NPC patients than in controls. For example, at an IgG titer of greater than or equal to 320, the prevalence rate was 82% in the NPC patient group and 1.7% in the controls (P less than 0.0001). The prevalence of EBV IgA anti-VCA antibodies (greater than or equal to 10) was significantly higher in the NPC patients than in control and family groups (82% vs 6.1% and 0%, respectively). The prevalence rate for elevated EBV IgA anti-VCA (greater than or equal to 20) was found to be significantly higher (P less than 0.0001) in NPC patients than in the control group (70% vs. 1.7%). A significantly high proportion (P = 0.0004) of NPC patients who had serum EBV IgA anti-VCA titers of less than 20 had elevated IgG titers to VCA greater than or equal to 320 (21% vs 1.7% among controls). It appears that testing for IgG antibodies at a serum dilution of 1:320 and for IgA antibodies at a dilution of 1:20 by the IPA technique comprises the best combination for the differentiation between NPC patients and health controls (91% vs 3.4%), and it is suggested that these be used as screening markers for NPC patients.     

Synthetic peptides deduced from the amino acid sequence of Epstein-Barr virus nuclear antigen 6 (EBNA 6): Antigenic properties,production of monoreactive reagents,and analysis of antibody responses in man

Studies on the antibody responses to various Epstein-Barr virus (EBV) antigens have been instrumental in the understanding of the seroepidemiology and diagnosis of this viral infection and the subsequent carrier state. While antibodies to the viral capsid antigen (VCA), early antigen (EA), and nuclear antigens 1 and 2 (EBNA 1 and 2) have been well characterized, the antibody response to the other nuclear antigens is not well understood. EBNA 6 is expressed by lymphoblasts during acute EBV infection and may be an important antigen for diagnosis and evaluation of the immune response. In order to analyze the antibody response to EBNA 6, ten peptides (20–21 amino acids), deduced from the EBNA 6 coding region, were synthesized and evaluated for antigenicity by ELISA. One peptide (p-63; PA-PQAPYQGYQEPPAPQAPY) derived from the amino acid repeats showed the highest specific reactivity with human sera. This peptide was evaluated further for detection of human EBNA 6-reactive antibodies. Forty-two of forty-nine (86%) EBV-seropositive healthy donors had p-63- specific IgG reactivity, while none of 50 EBV seronegative patients reacted with the p-63 peptide. Twenty-two of fifty-one (43%) patients with ongoing primary EBV infection had detectable p-63-specific IgG. Serum samples drawn sequentially from patients during and after primary EBV infection revealed an increase in p-63-reactive IgG over time. A similar pattern was found for reactivity with an EBNA I-specific peptide (p-107), in contrast to the EBNA 2 (polyproline) response, which decreased over time. Some EBV seropositive individuals who had no detectable IgG against peptide p-63 did have antibodies against the native EBNA 6 by anticomplement immunofluorescence to EBNA 6 transfected cells. Rabbit antiserum raised against p-63 reacted specifically with native EBNA 6 by an immunofluorescence assay and by immunoblotting, indicating the EBNA 6-specific antigenicity of the peptide. Thus, the peptide p-63 derived from the amino acid repeats of the EBNA 6 coding region constitutes a predominant, although not exclusive, epitope in the EBNA 6 antibody response. © 1995 Wiley-Liss, Inc.     

Antiviral antibodies in the sera of homosexual men: correlation with their lifestyle and drug usage

Healthy homosexual men between the ages of 21 and 65 years, from the Washington, DC (n = 162), and New York City (n = 89) areas, were studied for antibodies in the serum against cytomegalovirus (CMV), herpes simplex virus (HSV) types 1 and 2, and Epstein Barr virus (EBV) viral capsid antigen (VCA). CMV-specific antibodies were assayed by enzyme-linked immunosorbent assay (ELISA), anti-HSV-1 and -2 antibodies were measured by indirect hemagglutination (IHA), and antibodies to EBV VCA were measured by the immunofluorescence assay. Antibodies to human T lymphotrophic virus III (HTLV-III) were detected by ELISA and Western blot procedures. T lymphocytes were enumerated using OKT4 monoclonal antibody. Healthy male volunteer blood donors (n = 90) matched for age range and race proportions were used as controls. The percentage of seropositive individuals in the homosexual group was higher (90-98%) for all the viruses tested than in the control group (47-87%). Comparisons of the geometric mean titers, expressed as reciprocal serum dilutions, of seropositive individuals in homosexual (H) vs control (C) group were as follows: CMV-IgG (ELISA) H = 1:794, C = 1:68; HSV-1 (IHA) H = 1:248, C = 1:14; HSV-2 (IHA) H = 1:56, C = 1:17; EBV-VCA (IFA) H = 1:385, C = 1:131. The homosexual group also showed a higher frequency of individuals with elevated titers than the control group. The CMV IgM antibody was prevalent in 17.7% of the homosexual group and 5% of the control group; arithmetic means for ELISA values for CMV IgM were 0.207 for the homosexual group and 0.05 for the control group. In the homosexual group, the anti-CMV antibody titers increased with age (P = 0.01) and with numbers of sex partners (P = 0.06). Both anti-HSV-1 and anti-HSV-2 antibodies correlated with the number of sex partners (P = 0.04 and P = 0.05, respectively). Neither age nor partner number correlated with response to EBV, and no particular sex act was related to the EBV VCA titer level. HTLV-III seropositivity was associated with higher herpes virus group antibody titers, probably because of life style cofactors. Among the HTLV-III-seropositive subjects, those with less than or equal to 400 T-helper lymphocytes/mm3 had lower antibody titers than those with greater than 400 T-helper lymphocytes/mm3 counts, suggesting an impaired immune response secondary to immunosuppression.     

Stress-related Epstein–Barr virus reactivation

Epstein–Barr virus (EBV) remains latent in 90% of the patients following primary infection. The infection might be reactivated due to various stress factors. We, therefore, examined the levels of stress hormones (epinephrine, norepinephrine and cortisol), viral capsid antigen (VCA) immunoglobulin Ig G, VCA IgM, EBV early antigen IgG, Epstein–Barr nuclear antigen (EBNA) IgG, EBNA IgM antibody screening tests and performed EBV polymerized chain reaction (PCR) test and EBV DNA PCR in 100 draftees on their first day of recruitment and at the end of 1 month. Examination of the initial samples revealed that 94 (94%) subjects previously had EBV infection and 6 (6%) were seronegative. Second samples obtained at the end of first month showed that 7 (7.4%) reactivations occurred in 94 subjects who previously had EBV infection (P < 0.001). Two out of six (33.3%) who were initially seronegative had acute infection (P = 0.289). There was no significant difference between the median values of the levels of stress hormones in the initial and second serum and plasma samples. There was a significant difference between the rates of acute infection and reactivation among subjects with elevated cortisol and epinephrine levels in the second samples compared to subjects with normal levels (P < 0.001). No significant difference was determined between the first and second sample hormone levels of all nine subjects whose EBV-DNA turned positive. Routine examinations might not reveal any specific findings since EBV infection often has an asymptomatic course. EBV reactivations should always be kept in mind in patients subject to such stressful conditions.     

Rheumatoid factor as a cause of positive reactions in tests for Epstein–Barr virus-specific IgM antibodies

Sera from twenty-eight patients with rheumatoid arthritis (RA) were titrated in indirect immunofluorescence tests for Epstein–Barr virus (EBV) specific antibodies. All had IgG antibodies to viral capsid antigen (VCA), 64% at titres [unk] 320, and 71% reacted also in tests for VCA-specific IgM antibodies at titres ranging from 20 to 640. The reactions observed in the IgM test were not due to VCA-specific IgM antibodies, however, but rather to rheumatoid factor (RF) usually an IgM antibody to the Fc regions of IgG. The titres recorded in the anti-VCA IgM test correlated significantly with the RF titres and both reactivities were abolished by adsorption onto IgG coated latex particles. In addition, they clearly depended upon the height of the IgG antibody titre to VCA, indicating that the more VCA-specific IgG molecules are present the more likely it is that RF will combine with them in sufficient quantity before or after their attachment to VCA-positive test cells so as to become detectable by the fluorescent antibodies to human IgM. Results comparable in every aspect were obtained with those sera from patients with Hodgkin's disease, nasopharyngeal or cervical carcinomas which reacted in the anti-VCA IgM test. Sera from patients with infectious mononucleosis may also contain RF, but in such cases its removal by adsorption onto IgG-coated latex particles did not generally reduce the VCA-specific IgM antibody titre. Removal of RF from any of the sera studied did not affect the titres of VCA-specific IgG and, where applicable, IgA or heterophil antibody titres. These results re-emphasize the pitfall created by RF noted previously in tests for virus-specific IgM antibodies.     

Epstein-Barr virus antibodies in Kawasaki disease

The prevalent ages at onset for Kawasaki Disease (KD) and Epstein-Barr virus (EBV) infection are known to be similar in Korea and Japan. We evaluated the correlation between EBV infection and KD. The antibodies to EBV such as anti-viral capsid antigen (VCA) IgG and IgM, anti-diffuse and restricted early antigen IgG (anti-EADR IgG), and the anti-EBV determined nuclear antigen IgG (anti-EBNA IgG) were examined in 29 KD patients at five separate times sequentially during a period of one year, and also in 14 other children with a past history of KD. The results of each group were compared with those of age-matched controls. The positive rates of anti-VCA IgG and IgM at presentation in the KD patients were 41.4% (12/29) and 0% (0/29), respectively. Only one patient was found to be anti-VCA IgM-positive within two months. There were no cases of anti-VCA IgG except one, anti-EADR IgG and anti-EBNA IgG positive to negative seroconversion during the year. The children with a past history of KD showed higher anti-EBNA IgG-positive rates than the controls (p=0.04). There was no difference in the seropositive rates of the antibodies to EBV, cytomegalovirus, herpes simplex virus and herpes zoster virus. In conclusion, children with KD were noted to have normal immune responses to EBV infection. Children with a past history of KD seemed to be infected with EBV at a later age than children with no history of KD.     

Epstein-Barr virus (EBV) DNA levels in palatine tonsils and autologous serum from EBV carriers

A real-time polymerase chain reaction was employed to detect and quantitate Epstein-Barr virus (EBV) DNA in tonsils and autologous sera from EBV-seropositive children. EBV DNA was found in 95% of tonsils from 21 children and in 50% from 18 children with serum IgG titers to the virus capsid antigen (VCA) of > or =1:160 and 1:10 to 1:80, respectively (P = 0.002). Tonsils from children with titers > or =1:160 harbored more EBV DNA copies per mg tissue (mean, 1,237; range, < 2-13,998) than from children with titers 1:10 to 1:80 (mean, 23; range, < 2-226; P < 0.0001). By contrast, EBV DNA was detected only in serum from 25% of 20 children with titers > or = 1:160. Thus, ample differences in tonsillar EBV replication are mirrored inconstantly by detectable EBV in autologous serum suggesting that EBV DNA quantitation in tonsils may serve for refined monitoring of individuals at risk of EBV-associated lymphoproliferation.