EA IgG Research Articles

Epstein-Barr virus dynamics and its prognostic impact on nasopharyngeal cancers in a non-endemic region.

Epstein-Barr virus (EBV) DNA quantification in nasopharyngeal cancer (NPC) is an indicator of the tumour burden, stage and survival. Although EBV dynamics in endemic regions has been extensively studied and reported, the data from non-endemic regions is sparse. This study attempts to investigate the EBV dynamics in NPC patients from a non-endemic region and also to identify the factors impacting the outcomes. This was a prospective observational study conducted at a tertiary care centre in South India and enrolled patients with non-metastatic, biopsy proven NPC, who were suitable for radical chemo-radiotherapy with or without induction chemotherapy. Two blood samples, one prior to initiation of any anticancer treatment, and second at 6 weeks post treatment, were collected to quantify EBV DNA using real-time quantitative polymerase chain reaction. Antibodies against EBV viral capsid antigen (EBV VCA IgM), EBV Early Antigen (EBV EA IgG) and EBV Nuclear Antigen (EBV EBNA IgG) were also measured in the sample. The impact of EBV dynamics on the outcomes was then analysed. The study included a total of 35 patients. Thirty-three had identifiable EBV DNA (94.3%) and a histological diagnosis of non-keratinising undifferentiated type of squamous cell carcinoma. There was no correlation between the EBV DNA and anti-EBV antibodies. There was a significant association between composite stage and pre-treatment DNA titre (p = 0.030). The mean EBV DNA titre was lower for patients with no clinically demonstrable disease at last follow-up and the reduction in EBV DNA titres was significant (p = 0.020) for those patients who remained disease free. Plasma EBV DNA is an accurate and reliable biomarker for NPC for WHO type 2 and 3 tumours even in non-endemic regions.

Epidemiological characteristics of Epstein–Barr virus infection

Introduction. The Epstein–Barr virus (EBV) is one of the most common pathogens — it infects 90% of the world’s population. However, specific characteristics of the EBV infection epidemic process remain unidentified. The previous studies focusing on assessment of incidence rates for infectious mononucleosis (IM) tend to ignore the serological status of the population.The aim of the study was to identify epidemiological characteristics and assess the prevalence of serological markers for EBV infection for further epidemic control measures development.Materials and methods. In Moscow, the thorough analysis was performed using the data on IM incidence (Form 2 "Data on Infectious and Parasitic Diseases") and test results for 138,232 people checked for presence of VCA IgG, EBNA IgG, VCA IgM, EA IgG, and EBV DNA in their blood and saliva in 2011–2020.Results. The periodic pattern of IM incidence was discovered, demonstrating the repetitive peaks every 9 to 11 years and a strong direct correlative relationship with detection rates for active EBV infection markers. The intra-annual dynamics of IM incidence is characterized by a seasonal upswing during cold seasons of the year, reaching its peaks in October, November, or February and associated with a marked decrease in the VCA IgG and EBNA IgG seroprevalence. Children within the 1 to 17-year age range are groups at risk for acquiring primary infection, demonstrating significantly lower detection rates for chronic EBV infection (VCA IgG and EBNA IgG) markers and higher rates for VCA IgM and EBV DNA markers in blood compared to adults. The contribution of adult population to the epidemic process is formed through reactivation of chronic infection, which is observed primarily among women.Conclusion. The identified characteristics are essential for comprehensive understanding of the EBV infection epidemic process and can be used for developing preventive and anti-epidemic measures.

Study of Epstein–Barr virus serological profile in Egyptian patients with Hashimoto’s thyroiditis: A case-control study

BackgroundHashimoto’s thyroiditis (HT) is now considered one of the most prevalent autoimmune diseases. The aim of the present study was to determine the prevalence of different types of EBV antibodies in patients with HT in comparison to healthy controls, and to detect any correlation between EBV serological markers and different laboratory findings in HT patients. Subjects & methodsThis case-control study was conducted on 120 subjects divided into two groups: Sixty patients with HT (patients group), and sixty age and sex matched healthy volunteers (control group). All the participants were subjected to: Thyroid ultrasound, laboratory assessment including: Serum thyroid -stimulating hormone (TSH), free tetraiodothyronine (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase antibody (anti-TPO Ab) and anti-thyroglobulin antibody (anti-TG Ab). Four types of EBV antibodies (VCA IgM, VCA IgG, EA IgG, and EBNA-1IgG) were measured in serum using ELISA. ResultsThe mean serum levels of EBV VCA IgG and EA IgG were significantly higher in HT patients group in comparison to control group. In euthyroid HT patients, a significant positive correlation was observed between the age and EBV EA IgG. While in hypothyroid HT patients, a significant positive correlation between thyroid isthmus and EBNA-1IgG was observed. A significant negative correlation was found between the serum FT3 and EBNA-1IgG and a significant positive correlation was observed between serum TSH and EBV VCA IgG. ConclusionsThe high serum levels of EBV VCA IgG and EBV EA IgG in patients with HT suggest a possible association between EBV and HT.

Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein–Barr virus (EBV)‐associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost‐effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI‐W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI‐W 121 bp and ebv‐miR‐BART7‐3p were validated. Hsa‐miR‐29a‐3p and hsa‐miR‐103a‐3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI‐W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.

Infectious mononucleosis in splenectomised patient

Introduction: Infectious mononucleosis is one of the most common syndromes in our clinical practice. It is characterized by elevated temperature, pharyngitis and generalized lymphadenopathy.Objectives: To describe a clinical charachteristics of infectious mononucleosis (IM) caused by the Epstein Barr virus (EBV) in splenectomized patients since in the literature we found insufficient data.Subjects and Methods: Retrospective analysis of medical documentation of the patient treated in the Clinic for Infectious Diseases of the University Clinical Center of Republic of Srpska.Results: We have described the case of infectious mononucleosis, caused by Epstein Barr virus in a splenectomized patient. In support of acute EBV viral infection were the presence of lymphadenopathy, pharyngitis, hepatomegaly, as well as the occurrence of a typical generalized maculopapulous rash, and positive ELISA EBV VCA IgM and anti EBV VCA / EA IgG, were reported. According to the aforementioned patient, it fulfilled most criteria for setting the diagnosis of acute EBV infectious mononucleosis. Our patient showed some atypical signs such as absence of fever during hospitalization, marked leukocytosis with lymphocytosis (with a maximum increase in leukocyte count at 37.3 x 109, in the differential blood sample dominated lymphocytes with 29.96 x 109 (reference values 1.1-3.35), i.e. 80.3% (Ref. 20.0-46.0). Due to the maintenance of leukocytosis with lymphocytosis, the range of clinical has been extended trials (US abdomen, US neck, CT neck, chest, abdomen and pelvis, sternal puncture, hematologists' consultation). Based on the aforementioned hematologists' consultation, and post-release and recovery monitoring it is concluded that there has been no sign of acute hematologic disease but it has been just EBV-IM.Conclusion: Because of insufficient data on clinical presentation of Epstein Barr viral infections in splenectomized this we believe that this is one of the clinical variants although the possibility of individual variation cannot be excluded. Briefly, we can conclude that the immune system in the splenectomized patient can greatly modify the clinical presentation of Epstein barr viral infection, with the pathogenic mechanism that are still unclear.. However, due to the variety of clinical syndromes and the oncogenic potency of the Epstein-Barr virus, we should be extremely cautious and sometimes expand the diagnostic range beyond conventional examinations.

Seroprevalence of EBV in children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) accounts for about 25 percent of all childhood cancers and 75–85 % of all childhood leukemias. Thirty six children with acute lymphoblastic leukaemia were tested for antibodies to Epstein-Barr (EBV) virus with age ranged (2-12) years (20 males and 16 females) attending pediatric central hospital, oncology-hematology department .Thirty children with age ranged (2-12) years were regarded as control group. The two groups undergo Epstein-Barr virus antibodies assays (EBV-EAIgG, IgM, EBV-VCAIgG, and IgM) by enzyme linked immunosorbent assay (ELISA). The samples analysis was observed that the percentage of VCA-IgG (44.4%), VCA IgM (2.7%), EA IgG (27.7%) and EA IgM (2.7%) were higher than control group. The mean values of EBV (VCA IgG) in ALL group increase significantly when compared with control group, while no significant difference between ALL and control in the mean values of VCA IgM. There was a significant increase in the mean of EA IgG in ALL than in control group, whereas, no significant differences were noticed in EA IgM between two groups. These results clearly indicated that provide a working hypothesis and some facts on which further investigations of etiology of ALL be planned.

Evaluation of the significance of EBV nucleic acid and serology tests in the management of EBV-related diseases

Objective To investigate the relationship between Epstein-Barr virus (EBV) DNA and EBV serology markers and evaluate the clinical application values in different diseases. Methods Plasma samples from 397 diagnosed EBV infection-associated patients and 120 health donors from May 2014 to November 2015 in Wuhan Tongji Hospital were collected. Real-time fluorescent quantitative PCR was performed to detect the levels of EBV-DNA in peripheral blood mononuclear cell and plasma. ELISA was used to detect VCA IgA, VCA IgM, VCA IgG, EA(D) IgG and EBNA IgG antibodies in plasma. The positive rate of EBV-DNA and EBV antibodies were counted in each group according to the detection threshold.Kappa statistic and Spearman sank correlation test were used to analysis the correlation and uniformity between EBV-DNA and EBV serology indicators. Results The positive rate of VCA IgG in patient and health control was 94.2% (374/397) and 93.3% (112/120) respectively (χ2=0.125, P=0.67); The positive rate of EBNA IgG in patient and health control was 95.4% (379/397) and 95.0% (114/120) respectively (χ2=0.045, P=0.807); but the positive rate of VCA IgM was 5.5% (22/397) and 0% (0/120) respectively (χ2=6.9, P<0.01); The positive rate of VCA IgA was 43.3% (172/397) and 9.2% (10/120) respectively (χ2=49.5, P<0.01); The positive rate of EA(D) IgG was 42.0% (167/397) and 7.5% (9/120) respectively (χ2=49, P<0.01). The positive rate of EBV-DNA was 65.5% (260/397) and 16.7% (20/120) respectively (χ2=88.5, P<0.01); The positive rate of EBV-DNA in plasma was 45.8% (182/397) and 5.0% (6/120) respectively (χ2=66.4, P<0.01). Furthermore, the uniformity and Spearman correlation analysis showed that there was no significant correlation between EBV-DNA and EBV serology indicators. The correlation analysis between PBMC EBV-DNA and VCA IgM, VCA IgA, EA(D) IgG showed the Kappa was 0.073, 0.147, 0.073, respectively; the correlation analysis between plasma EBV-DNA and VCA IgM, VCA IgA, EA(D) IgG showed the Kappa was 0.144, 0.369, 0.288, respectively. Thus, the patients were divided into different groups according to the discharge diagnosis, it was observed that the positive rates of EBV-DNA is more than 90% in extra-nodal NK/T cells lymphoma, EBV-associated hemophagocytic lymphoid tissue hyperplasia, chronic active EBV infection and infectious mononucleosis. In nasopharyngeal carcinoma patients, the positive rate of EBV antibodies (VCA IgA and EA(D) IgG) were higher than the detection of EBV-DNA. Conclusions There was no significant correlation between EBV-DNA and EBV serology markers for the same sample. The clinical application values of EBV DNA and EBV serology markers were not identical in nasopharyngeal carcinoma, extra-nodal NK/T cells lymphoma, infectious mononucleosis and EBV-associated hemophagocytic lymphoid tissue hyperplasia. (Chin J Lab Med, 2017, 40: 195-200) Key words: Herpesvirus 4, human; DNA, viral; Serologic tests; Nasopharyngeal neoplasms; Lymphoma

Elevated antinuclear antibodies and altered anti-Epstein-Barr virus immune responses

It has been shown that Epstein-Barr virus (EBV) is able to alter the immune response towards self-antigens and may enhance risk of autoimmune diseases such as systemic lupus erythematosus (SLE) in genetically predisposed individuals. In this study, we evaluated the specific antibody immune response against EBV in patients with anti-nuclear autoantibodies (ANA) in comparison with ANA-negative healthy controls. For this purpose, 92 patients with an high anti-ANA reactivity with or without concomitant extractable nuclear antigen (ENA) or double stranded DNA (dsDNA) positivity were selected and compared with 146 healthy donors. We found that anti-EBV-VCA and EA IgG concentrations were significantly higher in ANA-positive patients in comparison to the controls (VCA P<0.0001 and EA P<0,03) as well as in those ANA-positive patients that showed a concomitant ENA positivity (P=0.0002). Interestingly, elevated anti-EBNA-1 IgG was found in a group of patients who had anti SSA/Ro antibodies. Anti-VCA IgM Abs were more frequently found in those patients with a very high titer of ANA (P=0.06); moreover detection of anti-VCA IgM/IgG in absence of anti-EBNA-1 IgG was more frequent in the patient than in the control group. Both these conditions correlate with a recent EBV infection or reactivation. The data suggest that EBV, particularly during acute infection or in its reactivation phase, could be involved in the ANA and ENA autoantibody formation.

Epstein-Barr virus viral load and serology in childhood non-Hodgkin's lymphoma and chronic inflammatory conditions in Uganda: implications for disease risk and characteristics.

Epstein-Barr virus (EBV) has been linked to malignancies and chronic inflammatory conditions. In this study, EBV detection was compared in children with non-Hodgkin's lymphoma and children with chronic inflammatory conditions, using samples and data from a case-control study carried out at the Mulago National Referral Hospital between 2004 and 2008. EBV viral load was measured in saliva, whole blood and white blood cells by real-time PCR. Serological values for IgG-VCA, EBNA1, and EAd-IgG were compared in non-Hodgkin's lymphoma and chronic inflammatory conditions; and in Burkitt's lymphoma and other subtypes of non-Hodgkin's lymphoma. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Of the 127 children included (87 males and 40 females; median age 7 years, range 2-17), 96 had non-Hodgkin's lymphoma (46 Burkitt's lymphoma and 50 other non-Hodgkin's lymphoma), 31 had chronic inflammatory conditions, and only 10% were HIV-positive. The most common clinical presentations for all disease categories considered were fever, night sweats, and weight loss. EBV viral load in whole blood was elevated in Burkitt's lymphoma compared to other non-Hodgkin's lymphoma (OR 6.67, 95% CI 1.32, 33.69; P-value = 0.04), but EBV viral loads in saliva and white blood cells were not different in any of the disease categories considered. A significant difference in EAd-IgG was observed when non-Hodgkin's lymphoma was compared with chronic inflammatory conditions (OR 0.19, 95% CI 0.07, 0.51; P-value = 0.001). When compared to chronic inflammatory conditions, EBV viral load was elevated in Burkitt's lymphoma, and EA IgG was higher in non-Hodgkin's lymphoma. This study supports an association between virological and serological markers of EBV and childhood non-Hodgkin's lymphoma, irrespective of subtype, in Uganda.

Effect of high dose vitamin C on Epstein-Barr viral infection.

BackgroundMany natural compounds were tested for the ability to suppress viral replication. The present manuscript details an analysis of high dose vitamin C therapy on patients with EBV infection.Material/MethodsThe data were obtained from the patient history database at the Riordan Clinic. Among people in our database who were treated with intravenous vitamin C (7.5 g to 50 g infusions) between 1997 and 2006, 178 patients showed elevated levels of EBV EA IgG (range 25 to 211 AU) and 40 showed elevated levels of EBV VCA IgM (range 25 to 140 AU). Most of these patients had a diagnosis of chronic fatigue syndrome, with the rest being diagnosed as having mononucleosis, fatigue, or EBV infection.ResultsOur data provide evidence that high dose intravenous vitamin C therapy has a positive effect on disease duration and reduction of viral antibody levels.Plasma levels of ascorbic acid and vitamin D were correlated with levels of antibodies to EBV. We found an inverse correlation between EBV VCA IgM and vitamin C in plasma in patients with mononucleosis and CFS meaning that patients with high levels of vitamin C tended to have lower levels of antigens in the acute state of disease.In addition, a relation was found between vitamin D levels and EBV EA IgG with lower levels of EBV early antigen IgG for higher levels of vitamin D.ConclusionsThe clinical study of ascorbic acid and EBV infection showed the reduction in EBV EA IgG and EBV VCA IgM antibody levels over time during IVC therapy that is consistent with observations from the literature that millimolar levels of ascorbate hinder viral infection and replication in vitro.

Determination of serological profiles and avidity of specific antibodies in the sera of patients with potential Epstein-Barr virus (EBV) infection

Epstein-Barr Virus, frequently referred to as EBV, is a member of the herpesvirus family and one of the most common human viruses. The virus occurs worldwide, and most people become infected with EBV sometime during their lives. The purpose of this study was to investigate the serological profiles of specific antibodies among the sera of suspected EBV infection patients along with VCA-IgG avidity. A total of 522 patient's sera were sent to The Clinical Microbiology Laboratory for EBV specific antibody detection and were studied by IFA method during a two year period. The serum samples were tested for EBV specific VCA IgG, VCA IgM, EA, EBNA antibodies and VCA IgG aviditity. Among 33 patients those who had low avidity for VCA IgG, 27 (81.8 %) of them had a serologic profile as follows; positive VCA IgG, negative VCA IgM, negative EA and negative EBNA. While this profile is considered as a primary infection, the frequency of the coexistence of VCA IgG low avidity with this profile is interpreted that avidity may lead to detect primary infection (Tab. 2, Ref. 25)

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.

PX-11 About the clinical benefits of EBV markers (EA IgG, VCA IGM, VCA IgG and EBNA IgG) in the diagnosis of infectious mononucleosis diagnosis: comparative responses of 2 automated methods VIDAS and Liaison

PX-11 About the clinical benefits of EBV markers (EA IgG, VCA IGM, VCA IgG and EBNA IgG) in the diagnosis of infectious mononucleosis diagnosis: comparative responses of 2 automated methods VIDAS and Liaison

Concentrations of organohalogen compounds and titres of antibodies to Epstein-Barr virus antigens and the risk for non-Hodgkin lymphoma

Exposure to some pesticides and persistent organic pollutants (POPs) has been indicated to be a risk factor for non-Hodgkin's lymphoma (NHL). Epstein-Barr virus (EBV) has been associated with some subgroups of NHL. In a previous study we found an interaction between high concentrations of some POPs and titres of antibodies to EBV early antigen (EA IgG) in relation to NHL. In the present study we measured lipid adjusted plasma concentrations of 35 congeners of polychlorinated biphenyls (PCB), p,p'-dichlorodiphenyldichloroethyelene (p,p'-DDE), hexachlorobenzene (HCB), seven subgroups of chlordanes (cis-heptachlorepoxide, cis-chlordane, trans-chlordane, oxychlordane, MC6, trans-nonachlordane, cis-nonachlordane) and one polybrominated diphenylether (PBDE) congener (no. 47) in 99 cases with NHL and 99 population based controls. Odds ratios (OR) for NHL were estimated. Sum of PCBs > median in the controls gave odds ratio (OR) 2.0, 95% confidence interval (CI) 0.99-3.9. High sum of chlordanes yielded OR 2.3, 95% CI 1.2-4.5. An interaction with EBV EA IgG was found. High sum of PCB gave OR 5.2, 95% CI 1.9-14 in the group with EA IgG > 40. Similarly HCB yielded OR 5.3, 95% CI 1.9-15, pp'-DDE gave OR 3.3, 95% CI 1.4-7.7 and sum of chlordanes yielded OR 6.8, 95% CI 2.3-20, whereas no association was found with PBDE. In summary, this study confirmed an association between certain POPs and NHL with an interaction with titre of IgG antibody to EBV EA.

Incidence of Reactive Antibodies Against Epstein-Barr in a Group of Renal Transplant Patients

Epstein-Barr virus (EBV) infection which is common among immunocompromised patients, may lead to life threatening lymphoproliferative diseases. In this study we examined the incidence and serologic status of EBV infection in 116 renal transplant patients including 84 males and 32 females as well as 72 normal volunteers. The time interval between transplantation and sampling was 1 month to 10 years. Twenty-two patients had a history of rejection. All cases were first transplants except for 3 second transplants. Four patients and no normals showed a positive PCR by a qualitative method. VCA IgM was positive in 11/116 patients (0.09%) and 3 of 72 (0.04%) normal volunteers. 99% (115/116) and 98% (65/72) of patients and normal controls were positive for VCA IgG. EA IgG was positive in 36/116 (31%) and 13/72(18%) of patients and normals, respectively. EBNA IgG was positive in 113/116 (97%) and 100% of patients versus normal controls, respectively. In all except one case with a positive VCA IgM there was a history of infectious mononucleosis-like syndrome. According to our previous data in more than 1000 renal transplant patients during more than 10 years, only one case of PTLD has been diagnosed (0.1%) which is lower than that reported. The high incidence of EBV seropositivity may contribute to this low incidence. The rate of EBV seropositivity in renal transplant patients was greater than in the normal population ( P = .05). No association was observed between PCR and seropositivity and rejection or the type of treatment. After this study we began routine PCR and antibody testing in all renal transplant patients both pre- and posttransplant to determine the exact rate of reactivation versus primary infection which we plan to evaluate after 2 to 3 years. In conclusion we believe that the best easiest method to detect EBV infection in immunocompromised patients is VCA IgM ELISA; a qualitative PCR alone is not sufficient for this evaluation.

Clinical correlates of circulating immune complex levels in advanced lung cancer. A discrimination analysis.

Sera from 53 patients with unresectable lung cancer were tested for the presence of immune complexes by 12 assays. 5 assays (EA rosette inhibition, ADCC inhibition, platelet aggregation, IgG and C3 concentrations in PEG precipitates) could discriminate cancer patients from healthy subjects with over 80% reliability. On the basis of 3 assays (EA-I, ADCC-I and PEG-C3) a function allowing a 100% correct classification could be formulated:--(EA-I)--0.5 (ADCC-I) + 2.4 (PEG-C3) greater than 69.3, i.e., results higher than 69.3 are characteristic for cancer patients and lower than 69.3 for normal subjects. The relationship between the immune complex levels and the average survival time was not altered by sex, age, histology and treatment. None of the immune complex assays or their combination were useful for the estimation of individual life expectation.

Effects of Staphylococcus aureus Cowan I bacteria on the immunoglobulin production from human B-cell subsets

Staphylococcus aureus Cowan I bacteria (SpA CoI) is known to be a polyclonal B-cell activator of human lymphocytes. In this study, we investigated which of the B-cell subsets SpA CoI could stimulate and induce immunoglobulin (Ig) production. B-Cell subsets were separated from peripheral blood and tonsil lymphocytes by rosette formation with E, EA IgG, EAC, anti-Ig-conjugated ox erythrocytes (OE-anti-Ig), and protein A-conjugated OE (OE-Pro A), or on a bovine serum albumin (BSA) discontinuous density gradient. The cells responding to SpA CoI included E −, C3 receptor-positive (C3R +), Fc receptor-negative (FcR −), and surface Ig-positive (SIg +) B-cell subsets. These B-cell populations responded well to SpA CoI and produced significant amounts of IgG, IgM, and a lesser amount of IgA. Among SIg + B cells, IgG, IgA, and IgM + B-cell subsets responded to SpA CoI and produced large amounts of Ig belonging to each corresponding Ig class. IgD + B cells failed to produce Ig of any class, except for minimal amounts of IgG and IgM. While both the protein A receptor-positive (Pro A · R +) and negative (Pro A · R −) cells responded well to SpA CoI, Pro A · R + B cells produced IgG mainly and Pro A · R − B cells produced IgM. Fractionation of B cells on a BSA gradient revealed that comparatively small-sized and denser B-cell subsets responded well to SpA CoI and produced every class of Ig.

Evidence that C1q, a Subcomponent of the First Component of Complement, is an Fc Receptor of Peritoneal and Alveolar Macrophages

Guinea pig peritoneal macrophages were cultured for 24 h in the presence of two inhibitors of the biosynthesis of collagen-like molecules such as C1q : 10 -3 M 3,4-dehydroproline or 10 -4 M 2,2′-dipyridyl. Their Fc-receptor activity was measured by rosette formation, using sheep erythrocytes (E) coated with rabbit anti-sheep IgG (EA IgG). The Fc-receptor activity was decreased by 40 to 70% of control cultures depending on the amount of IgG on the E. The activity of a second receptor on the macrophages, mediating the binding of C3b coated E, was not altered by this treatment. Rat alveolar macrophages were depleted of their Fc-receptor activity by pronase treatment (1.5 mg/ml) in the presence of 2,2′-dipyridyl. After washing the cells, the EA IgG-binding activity was restored to about half of the initial level within 2 h. With 2,2′-dipyridyl also present during the second incubation, the re-expression of the Fc-receptor activity was suppressed further. Preincubation of guinea pig peritoneal macrophages with anti-C1q-F(ab') 2 for 45 min at 37°C caused a dose-dependent reduction of the Fc-receptor activity, but not C3b receptor activity. These results support our hypothesis that C1q synthesized and secreted by macrophages serves as an Fc-receptor in the membrane during the secretion.

Surface markers on lymphocytes and cells of the mononuclear phagocyte series in skin sections in leprosy.

E, EA and EAC rosetting techniques and Ig fluorescence were used in a study of receptor sites in cryostat sections of lesions through the spectrum of leprosy, and for comparison in some other mycobacterial and granulomatous lesions. Anti-C3, and trypsin were used as blocking agents. Lymphocytes in borderline lepromatous leprosy produced EA adherence and IgG fluorescence indicating B type cells. Lymphocytes in tuberculoid leprosy produced neither E or EA adherence and no fluorescence; these cells were presumed to be T cells. EAC and EA adherence was more marked in areas of macrophage infiltration, where there were few lymphocytes, than over the lympocytes themselves. Two distinct patterns emerged: (i) EA binding together with IgG fluorescence was seen in active lepromatous leprosy and could be localised to the surface of individual macrophages, and (ii) EAC binding together with IgM fluorescence was seen in the granuloma of tuberculoid leprosy and sarcoidosis, but could not be definitely related to cell surface; rather it was diffusely spread over the whole granuloma; EAC adherence was diminished by anti-C3 serum. Trypsin removed EA binding completely, but only diminished EAC adherence. It is suggested that the EA pattern indicates immunoglobulin receptors on macrophage and lymphocyte surfaces: and that the EAC binding (which is stronger than EA) involves C3 and IgM receptors at extracellular sites as well as C3 receptor sites on epithelioid cell surfaces. EA and EAC binding were enhanced in borderline tuberculoid leprosy in reaction and erythema nodosum leprosum, suggesting that immunoglobulin and complement receptor sites increase in number with enhanced hypersensitivity.

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.