Early Antigen IgG Research Articles

Gene–environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis

Purpose To determine the role of gene–environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein–Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients. Methods A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained. There were 54 MS cases that underwent MRI and EBV-antibody assessments at the 3-year follow-up. The anti-EBV panel included measurements of the levels of anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgM and anti-EBV VCA IgG. The relationships between HLA alleles, anti-EBV antibody levels, MRI and clinical parameters were assessed in regression analysis. Results The presence of HLA B7 was associated with increased T1-LV and trends indicating increased anti-EBV VCA IgG levels, higher disability (EDSS) and more destructive MRI parameters (increased T2-LV and decreased BPF). The presence of HLA A2 was associated with lower EDSS and a trend toward decreased anti-EBV VCA IgG levels; the associations with MRI variables were not significant. The HLA B7–A2 haplotype was significantly associated with higher T2-LV and T1-LV and a trend toward lower BPF was observed. Conclusions Our data suggest that gene–environment interactions between specific HLA Class I loci and EBV exposure are associated with MRI markers of lesion injury and brain atrophy in MS patients.

Epstein–Barr virus is associated with grey matter atrophy in multiple sclerosis

Objective:The aim of the study was to determine whether the presence of anti-Epstein–Barr virus (EBV) antibodies is associated with MRI measures of brain injury and neurodegeneration in patients with multiple...

Serum antibody response to lytic and latent Epstein-Barr virus antigens in undifferentiated nasopharyngeal carcinoma patients from an area of nonendemicity.

Epstein-Barr virus (EBV)-associated undifferentiated carcinoma of the nasopharyngeal type (UCNT) is highly prevalent in southeast China, where immunoglobulin A (IgA) antibodies to viral capsid antigen and early antigen (EA) represent important markers, routinely used to assist in diagnosing this malignancy. Our study aimed at determining the EBV serological profiles of 78 UCNT patients from Italy, an area of nonendemicity for this tumor, using different assays specific for both lytic and latent EBV antigens. Serum IgA against both EA and EBNA1 and IgG and IgA to the latent membrane protein 1 (LMP1), to EA, and to the EBV transactivator ZEBRA protein were assessed. These serological responses were then evaluated according to the clinicopathologic parameters at diagnosis. The sensitivities of the IgG assays were 37.7% for LMP1, 73.6% for EA, and 61.0% for ZEBRA. EA/EBNA1 IgA reactivity was 84.4%, and a high association (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.7 to 4.0) with UCNT was observed. When EBV serological reactivities were analyzed according to the tumor, node, and metastasis staging system (TNM), a statistically significant association was found between N stage and IgG antibody rates for EA (OR, 3.6; 95% CI, 1.2 to 10.9) and ZEBRA (OR, 2.6; 95% CI, 1.2 to 5.5) and between M stage and IgG antibody rates for ZEBRA (OR, 7.1; 95% CI, 3.2 to 16.0) and LMP1 (OR, 14.0; 95% CI, 1.8 to 110.9). Our results show that no single serological marker allows the detection of all UCNT cases. EA/EBNA1 IgA represents a reliable marker for diagnosis, with a high predictive value also in areas where UCNT is not endemic, such as Italy. The analysis of serological results according to TNM classification is consistent with a progressive impairment of humoral immune response to EBV as the disease advances and may be used to improve the accuracy of diagnosis.

Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome

Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after a 3-6-week exposure to certain drugs, including anticonvulsants. There are some reports showing that serum IgG levels often decrease at the early stage of DIHS. Reactivation of human herpesvirus (HHV)-6 has been reported in patients with DIHS, and some other DIHS patients showed reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV). To determine whether reactivation of HHV-6, HHV-7, CMV and/or EBV occurs in patients with DIHS. Titres of IgG and IgM antibodies to HHV-6 and HHV-7 were determined using an indirect immunofluorescence antibody assay on admission and at various times after admission. Anti-CMV IgG and IgM antibody titres and anti-EBV capsid antigen IgG, IgA, IgM, and EBV nuclear antigen and EBV early antigen IgG titres were determined by enzyme immunoassay. Polymerase chain reaction (PCR) procedures for HHV-6, HHV-7, CMV and EBV DNAs were performed using serum samples. IgG antibody titres to HHV-6, HHV-7, CMV and EBV were increased after the onset in seven, six, seven and two of seven patients, respectively. IgG antibody titres to HHV-6 and HHV-7 were elevated simultaneously 21-38 days after the onset. IgG antibody titres to CMV and EBV were elevated 10-21 days after the elevation of HHV-6 and HHV-7 antibody titres. PCR showed that HHV-6, HHV-7, CMV and EBV DNAs became positive in six, five, seven and two of seven patients, respectively. HHV-6 and HHV-7 DNAs were detected 21-35 days after the onset, and CMV DNA was detected 10-21 days after detection of HHV-6 and HHV-7 DNAs. The present study suggests that in addition to HHV-6 reactivation, reactivation of HHV-7, CMV and/or EBV may also occur following drug eruption in some patients with DIHS.

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.

Adipose Tissue Concentrations of Dioxins and Dibenzofurans, Titers of Antibodies to Epstein–Barr Virus Early Antigen and the Risk for Non-Hodgkin Lymphoma

A rapid increase in the incidence of non-Hodgkin lymphoma (NHL) has been reported in many countries. Exposure to certain pesticides or organochlorines has been shown to be a risk factor. Epstein–Barr virus (EBV) is a human herpesvirus that has been associated with some subgroups of NHL, such as Burkitt lymphoma and lymphomas related to severe immunosuppression. In this study we measured concentrations of dioxins and dibenzofurans in 33 NHL cases and 39 surgical controls. For 23 of the cases and 32 of the controls EBV titers were also available. Median titer of antibodies to EBV early antigen (EA) IgG was higher in patients than in controls. Concentrations of dioxins and dibenzofurans were divided into two groups according to the median concentration for the controls. Unconditional logistic regression analysis was performed adjusting for sex, age, and body mass index. For several higher chlorinated congeners increased risk was found for patients in the high-concentration and high-titer group. For toxic equivalency factor >27.79 and EA>80 an odds ratio of 2.8 with 95% confidence interval 0.52–18 was calculated. These results indicated that current exposure to certain organochlorines in combination with EBV might increase the risk for NHL.

Concentrations of Organochlorines Related to Titers to Epstein-Barr Virus Early Antigen IgG as Risk Factors for Hairy Cell Leukemia

Concentrations of Organochlorines Related to Titers to Epstein-Barr Virus Early Antigen IgG as Risk Factors for Hairy Cell Leukemia

Epstein-Barr virus-specific antibodies in Epstein-Barr virus-positive and -negative gastric carcinoma cases in Japan.

We examined Epstein-Barr virus (EBV)-specific antibodies in serum samples from 64 and 59 patients with EBV-positive and -negative gastric carcinomas, respectively, and 73 healthy controls using immunofluorescence assays. EBV capsid antigen (VCA) IgG and EBV-determined nuclear antigen (EBNA) IgG were detected in all 196 subjects. The geometric mean titer (GMT) of VCA-IgG, but not EBNA-IgG, was higher in EBV-positive carcinoma cases than in EBV-negative carcinoma cases (P < 0.001). The seroprevalence rates of VCA-IgA and EBV early antigen (EA) IgG were higher in EBV-positive carcinoma cases than in EBV-negative carcinoma cases. Odds ratios (ORs) comparing seroprevalence rates between EBV-positive and -negative carcinoma cases were 3.4 (95% confidence interval [CI] = 1.3-8.8) and 6.6 (95% CI = 2.7-16.3) for VCA-IgA and EA-IgG, respectively. These results suggest that EBV reactivation occurs in vivo, since more than 90% of Japanese are infected with EBV in early childhood. The GMT of VCA-IgG in EBV-negative carcinoma cases was higher than that of healthy controls (P = 0.028). The seroprevalence rates of EA-IgG were greater in EBV-negative carcinoma cases than in healthy controls (OR = 4.9, 95% CI = 1.2-19. 7). VCA-IgA was the only antibody that showed a significantly high seroprevalence and GMT in EBV-positive carcinoma cases, but not in EBV-negative carcinoma cases. Thus, VCA-IgA can be a marker of immune response to EBV in EBV-positive carcinoma cases. Our findings support the hypothesis that if EBV is involved in the development of EBV-positive gastric carcinoma, the EBV reactivation occurs in vivo.

Concentrations of organochlorines related to titers to Epstein-Barr virus early antigen IgG as risk factors for hairy cell leukemia.

Hairy cell leukemia (HCL) is a rare chronic B-cell malignancy that, according to modern classifications, is a subgroup of non-Hodgkin lymphomas (NHLs). A rapid increase in incidence of NHL has been reported in many countries. The reasons for this increase are largely unknown, but exposure to organochlorines has been suggested as a risk factor. Epstein-Barr virus is a human herpesvirus that has been associated with certain subgroups of NHL. In this study, we measured lipid adjusted blood concentrations (in nanogram per gram) of 36 congeners of polychlorinated biphenyls (PCBs), p, p'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and four subgroups of chlordanes (trans-nonachlor, cis-nonachlor, MC6, and oxychlordane) in incident cases of HCL and controls from the general population. We obtained results on organochlorines and antibodies for 54 cases and 54 controls. Titers of antibodies to the Epstein-Barr early antigen and Epstein-Barr nuclear antigen, measured as P107, were correlated to concentrations of organochlorines to evaluate the possibility of an interaction between these factors in the pathogenesis of HCL. We found no significant difference in lipid-adjusted blood concentrations of total PCBs, p,p'-DDE, HCB, or the sum of the chlordanes between cases and controls. Titers of antibodies to Epstein-Barr early antigen IgG [Greater and equal to] 40 were correlated to an increased risk for HCL. This risk was further increased in those with a level above the median value of p,p'-DDE, HCB, or the sum of the chlordanes, suggesting an interaction between Epstein-Barr virus and a higher concentration of these chemicals. We also found increased risk for the sum of immunotoxic PCB group.

Concentrations of Organochlorines Related to Titers to Epstein-Barr Virus Early Antigen IgG as Risk Factors for Hairy Cell Leukemia

Concentrations of Organochlorines Related to Titers to Epstein-Barr Virus Early Antigen IgG as Risk Factors for Hairy Cell Leukemia

Epstein-Barr Virus Pcr Correlated with Viral Histology and Serology in Pediatric Liver Transplant Patients

Epstein-Barr virus (EBV)–associated illnesses in posttransplant patients are difficult to diagnose. Attempts to aid in the diagnosis of such illnesses using the polymerase chain reaction (PCR) analysis for EBV have met with variable success due to the potential exquisite sensitivity of the assay. We have designed a relatively insensitive EBV PCR assay and compared the results with objective evidence of EBV activity including serologic response and in situ hybridization for the EBV genome. Eighty-five specimens from 65 patients were analyzed by the EBV PCR using DNA from whole blood. EBV serologic evaluation was done on 53 of the samples and in situ hybridization for EBV (EBER-1 mRNA) on 46 paired liver biopsies. Of 85 samples, 25 (29%) were positive for EBV using the PCR assay. Intensity of amplification was graded 0.5–1+ (weak) to 3+ (strong). Using these criteria, 19 EBV PCR-positive samples were graded 0.5–1+, 5 were graded 2+, and 1 was graded 3+. Of the moderate to strongly positive samples (2+ or 3+), five of six had two or more EBER-1–positive cells in the liver biopsies. Of the remaining 40 liver biopsies with either negative or weak positive PCR results, 3 had only single cells positive for EBER-1; the remainder were negative. In addition, PCR-positive results correlated with increasing EBV anti–early antigen antibody (P = .005) and viral capsid antigen IgG immunoglobulin GVCA (P =. 05) EBV-positive results using the PCR assay correlated with objective evidence for increased EBV burden in children after liver transplantation. These preliminary data suggest that this PCR test may be useful to help guide immunosuppressive therapy in the posttransplant patient. Further evaluation using larger numbers of patients will be necessary to confirm this.

Comparison of diagnostic criteria for Epstein-Barr virus infection in children

Serum samples from 159 children with clinically diagnosed infectious mononucleosis, were compared by different serodiagnostic tests for Epstein-Barr infection. These were: 1. detection of viral capsid antigen IgM; 2. detection of viral capsid antigen IgG in absence of nuclear antigen antibodies; 3. detection of IgG to early antigen; and 4. detection of heterophil antibodies. Heterophil antibodies detection is not suitable for diagnosing infectious mononucleosis among children below 6 y. The serological diagnosis of Epstein-Barr virus (EBV) infections must be done by detecting viral capsid antigen IgM, and/or viral capsid IgG in the absence of Epstein-Barr nuclear antigen antibodies. Early antigen IgG was shown on its own not to be a reliable diagnostic marker.

Human nasopharyngeal carcinomas positive for Epstein-Barr virus DNA in North America.

Nasopharyngeal carcinomas (NPC) from 2 black patients and 1 Caucasian patient were positive for Epstein-Barr virus (EBV) DNA. Of the tumors, 2 were lymphoepitheliomas (undifferentiated NPC) and 1 was a moderately differentiated NPC. All 3 patients had high IgG titers against EBV early antigen and high IgG and IgA titers against virus capsid antigen (VCA). In one patient, the levels of anti-VCA IgA were different than those of anti-VCA IgG over the course of the disease. Our data support the association of EBV and NPC in North America.