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C Baboonian

Publications and source records attributed to C Baboonian.

35 records · Page 2Linked to original sources
PubMed1991

Congenital and maternal cytomegalovirus infections in a London population.

OBJECTIVE: To determine if women at risk of having babies infected with cytomegalovirus (CMV) can be identified antenatally. DESIGN: Prospective serological and demographic study of pregnant women and virological study of their newborn infants. SETTING: Teaching hospital in London. SUBJECTS: 3315 pregnant women and 2737 of their babies. MAIN OUTCOME MEASURES: Quantitative detection of CMV IgG antibodies; qualitative detection of CMV IgM antibodies; demographic characteristics of mothers; qualitative and quantitative titration of CMV viruria in newborn. RESULTS: Congenital CMV infection was found in nine newborn babies (0.33%) two of whom had symptoms. Serological testing of the nine mothers showed four primary and five recurrent infections; both of the symptomatic children were born in the latter group. Testing for CMV specific IgM antibodies or quantitation of IgG antibodies in early pregnancy sera could not differentiate those women at risk of giving birth to babies infected or damaged by CMV from the rest of the population. Quantitation of viruria confirmed that those babies most at risk of CMV disease have the highest titres of CMV. CONCLUSIONS: (i) Since laboratory tests in pregnant women cannot reliably identify fetuses at risk of disease, screening for asymptomatic maternal infection coupled with termination of pregnancy cannot be recommended. (ii) Since 'immune' women can still give birth to babies affected by CMV, we propose that future CMV vaccines should be used to immunize children with the aim of eradicating CMV infection in preference to selective immunization of sero-susceptible females.

Adolescent↗
PubMed1991

Cross reaction of antibodies to a glycine/alanine repeat sequence of Epstein-Barr virus nuclear antigen-1 with collagen, cytokeratin, and actin.

P62 is a synthetic peptide which corresponds to the glycine/alanine repeat sequence of Epstein-Barr virus nuclear antigen-1. It is the main epitope recognised by anti-rheumatoid arthritis nuclear antigen antibodies. It was shown previously that anti-P62 antibodies were raised fourfold in patients with rheumatoid arthritis compared with controls. To examine the possibility that this increase was due to cross reactive autoantibodies binding to P62, anti-P62 antibodies from serum samples taken from 10 patients with rheumatoid arthritis and five healthy controls were purified by affinity chromatography. Immunoglobulin G anti-P62 antibodies purified from four of 10 serum samples from patients with rheumatoid arthritis also reacted with human epidermal keratin, denatured collagen type II and actin, but not with influenza antigens, as determined by enzyme linked immunosorbent assay (ELISA). Anti-P62 antibodies in serum samples from healthy controls and patients with rheumatoid arthritis reacted with epidermal keratin by immunoblotting. It is suggested that antibodies to the glycine/alanine repeat sequence of Epstein-Barr nuclear antigen-1 recognise homologous epitopes on keratin, actin, and collagen. It is also possible that molecular mimicry between a major epitope on the Epstein-Barr virus and several autoantigens might contribute to the breakdown of tolerance and autoimmunity in patients with rheumatoid arthritis.

Actins↗
PubMed1989

Complement-independent neutralising monoclonal antibody with differential reactivity for strains of human cytomegalovirus.

A mouse monoclonal antibody with complement-independent neutralising activity against cytomegalovirus (CMV) and reactive with the 86 kilodalton (kDa) viral glycoprotein H is described. Neutralisation tests against a range of different strains of CMV showed significant crossreactivity, but clear differences were evident between the two prototype viruses AD169 and Davis, and particularly between AD169 and several low-passage recent clinical isolates; CMV present in urine was neutralised weakly if at all.

Animals↗
PubMed1989

The response to Epstein-Barr virus infection in Sjögren's syndrome.

To assess the response to Epstein-Barr virus (EBV) infection in patients with primary Sjögren's syndrome (SS), the frequency of detection of EBV DNA was studied in salivary gland biopsies and the antibody and idiotypic response to the virus was compared with healthy controls and infectious mononucleosis (IM). Viral DNA, detected by in-situ hybridization, was found in biopsies from two out of 12 patients with SS and six out of 10 controls. IgG, IgA and IgM antibodies to the virus, measured by ELISA using synthetic peptides (early antigen and EBNA-1) and a cloned fusion protein (EBNA-1), were normal in sera from 20 patients with SS, whereas infectious mononucleosis patients showed an increase in IgM antibodies to EBNA-1 and IgG antibodies to early antigen. One similarity between infectious mononucleosis and Sjögren's syndrome was a significant increase in the germline heavy chain idiotype G6 in both diseases, suggesting activation of similar B-cell subsets. It is possible that this is due to EBV, though the low frequency of EBV DNA in biopsies and the normal levels of EBV antibodies in SS does not lend any evidence that the virus itself is the causative agent.

Antibodies, Viral↗
PubMed1989

Effect of pregnancy plasma upon in vitro parameters of cell mediated immunity.

Pregnant women were classified according to their serological status for cytomegalovirus, herpes simplex virus or rubella virus. Lymphocytes taken from non-pregnant women were shown to be able to recognise viral antigens and the mitogen phytohaemagglutinin by the measurement of proliferative responses and by the production of gamma interferon. Proliferative responses or gamma interferon production were greatly reduced in the presence of plasma taken during the first, second or third trimester and immediately post-partum. The responses then gradually returned to normal after delivery. The availability of serial sera taken before pregnancy as well as during and after pregnancy in individual women showed that this effect was maintained even when sera had been stored frozen for more than one year. Mixing experiments were performed to vary the proportion of pregnancy serum in any particular assay but this did not prove that pregnancy sera were actively suppressive. Instead, the data suggest that pregnancy sera are deficient in some factor or factors which are required to support lymphocyte proliferation. The effect was not attributable to the physiological haemodilution of pregnancy leading to a reduced concentration of putative factors nor could transferrin levels or the iron binding capacity of this protein be implicated.

Adult↗
PubMed1989

Responses to mitogenic stimulation of lymphocytes taken during and after pregnancy.

Serial blood samples were collected during pregnancy, after delivery and several months postnatally from 28 women. The blastogenic responses of lymphocytes to varying concentrations of phytohaemagglutinin (PHA) were tested using autologous plasma or fetal calf serum (FCS) to support the lymphocyte cultures. Using FCS, the blastogenic response decreased as pregnancy progressed and remained depressed months after delivery. In contrast, when autologous plasma was used a 10-fold higher concentration of PHA was required to give optimal stimulation. Blastogenic responses were still suppressed during pregnancy but had returned to initial values by the time of delivery and were greater still in the post-partum and postnatal periods. We conclude that the inherent ability of lymphocytes to undergo blastogenesis is suppressed during pregnancy but that this is over-shadowed by a humoral effect of pregnancy plasma. The significance of these results is discussed.

Blood Physiological Phenomena↗
PubMed1989

Antibodies in rheumatoid arthritis react specifically with the glycine alanine repeat sequence of Epstein-Barr nuclear antigen-1.

Antibodies to rheumatoid arthritis nuclear antigen (RANA) are four- to sixfold increased in sera from patients with rheumatoid arthritis (RA), whereas levels of antibodies to other EBV encoded antigens are slightly elevated or normal. We have demonstrated that the major epitopes recognised by anti-RANA antibodies are represented by a synthetic peptide, P62, corresponding to part of the internal repeat sequence which contains only the amino acids glycine and alanine. In an enzyme-linked immunosorbent assay, anti-P62 antibodies in rheumatoid arthritis sera were four fold higher than healthy and disease controls. By contrast, levels of antibodies to a cloned fusion protein, representing the C-terminus of EBNA-1 and excluding the IR3 region, were normal in RA, but elevated fivefold in nasopharyngeal carcinoma (NPC). Affinity purified anti-P62 antibodies reacted with EBNA-1 and RANA but also with a 60 kD protein present in tissue extracts which has been tentatively identified as cytokeratin. This suggests that the specific increase of anti-P62 antibodies in RA may be due to cross-reactions with autoantibodies to structural proteins with repeat sequences containing glycine. Such sequences are found in cytokeratin and proteoglycans, suggesting that anti-P62 (and hence anti-RANA) antibodies may be cross-reactive antibodies of pathogenic significance in RA, though not necessarily indicating an aetiological role for EBV.

Alanine↗
PubMed1989

Persistence of Epstein-Barr virus in salivary gland biopsies from healthy individuals and patients with Sjögren's syndrome.

Salivary gland biopsies from 12 patients with primary Sjögren's syndrome and 10 controls were examined for Epstein-Barr virus (EBV) DNA by in-situ hybridization and for EBV proteins by immunofluorescence and peroxidase techniques. Viral DNA was found in biopsies from two out of 12 patients with primary Sjögren's syndrome and six out of the 10 controls. The DNA and early antigen were in epithelial cells lining the ducts and acini, early antigen expression being limited to the luminal side of the epithelium. In eight biopsies studied with other antibodies, membrane antigen was identified in both acini and ducts but viral capsid antigen and Epstein-Barr nuclear antigen were not detected. EBV was found in biopsies from five of the controls without inflammation or Class II expression. This suggests that, in health, persistence and replication occur without inducing an immune response, possibly due to the restricted expression of early antigen on the luminal of the epithelium, away from immune surveillance. The inflammation in Sjögren's syndrome could be due to a breakdown of this unusual mechanism for viral persistence leading to a vigorous immune response to the virus. However our study provides no evidence to suggest that EBV infection load is increased in this disease.

Adolescent↗
PubMed1989

Virus infection induces redistribution and membrane localization of the nuclear antigen La (SS-B): a possible mechanism for autoimmunity.

To investigate the possibility that anti-La (SS-B) antibodies in Sjögren's syndrome were induced by virus infection we studied the distribution of La in virus-infected human cell lines. Three monoclonal antibodies to La were used with monoclonal anti-Sm (derived from MRL/lpr lupus mice) and anti-rat immunoglobulin antibodies as controls. In uninfected cells La was predominantly in the nucleus. Twenty-four hours after infection of HEp-2 cells with adenovirus 2, the La and Sm antigens appeared to aggregate and accumulate in the periphery of the nucleus and, after 48 h, La was seen in the cytoplasm and cell membrane. No cytoplasmic or membrane expression of Sm was seen. Infection with adenovirus or cytomegalovirus caused a 2-13-fold increase in the concentration of La in three cell lines. Treatment of HE--2 cells with interferon-gamma (IFN-gamma) and infection with Epstein-Barr virus and cytomegalovirus caused cytoplasmic, but no definite membrane expression of La. The appearance of La on the surface of virally infected epithelial cells together with IFN-gamma induced class II expression could form the basis of a T cell dependent mechanism for anti-La autoantibody induction.

Adenoviridae Infections↗
PubMed1987

Immunity to rubella among women of child-bearing age.

The results of testing for rubella antibodies in over 6000 sera from women of child-bearing age are reported and analysed according to pregnant state, age, country of origin and social class. There was no difference between the rubella seroprevalence rates in women who were pregnant and in those who were contemplating pregnancy in the future. Likewise, women (either pregnant or non-pregnant) who were young enough to have been offered rubella vaccine at school were not more likely to be immune to rubella than were older women. Rubella seropositivity rates were not influenced by social class but significantly higher rates were found in women born in European or Arabian than in African or Asian countries. We conclude that the national scheme for rubella immunization has not reduced the number of women susceptible to rubella entering pregnancy in this Health District and that greater attention should be paid to immunization of women of child-bearing age from African or Asian countries.

Adolescent↗
PubMed1985

The demographic characteristics of pregnant women infected with cytomegalovirus.

An analysis was made of the demographic characteristics of 1000 women who were screened for serological evidence of cytomegalovirus (CMV) infection while receiving antenatal care in central London. The prevalence of antibodies against CMV was shown, by multiple discriminant analysis, to be significantly associated with non-Caucasian race (p less than 0.001), increasing maternal age (p less than 0.001) and poor social class (p less than 0.05). These results are interpreted as reflecting increased childhood exposure to CMV as a result of poor social environments. When data from 48 women who acquired primary CMV during pregnancy were analysed, infection was also related to non-Caucasian race (p less than 0.01), but in contrast, there was no demonstrable effect of social class, maternal age or marital status. We conclude that pregnant women acquiring the form of CMV infection with the greatest pathological potential for the fetus (primary infection) belong primarily to the middle-class sections of communities. Since middle-class women traditionally avail themselves of prophylactic measures, this result provides some optimism for the ultimate control of this common disease by immunization.

Adolescent↗
PubMed1984

Intra-uterine transmission of cytomegalovirus in women known to be immune before conception.

A prospective study identified 785 pregnant women who had been shown to possess complement fixing antibodies against cytomegalovirus (CMV) during a previous pregnancy. As these women were thus known to have been immune prior to their subsequent conception, their neonates were examined for evidence of congenital CMV infection. Specimens were obtained from 725 (92%) of the neonates and congenital infection was found in only one (0.14%). The elder sister of the infected child was also shown, by retrospective testing of her stored cord serum for specific IgM antibodies, to have been infected in utero. Thus, one woman was identified who had delivered consecutive siblings congenitally infected with CMV. We conclude that some women have a propensity for intra-uterine transmission of CMV, despite being immune prior to conception, and speculate that such women may have acquired their infections perinatally.

Adult↗
PubMed1984

A prospective study of primary cytomegalovirus infection during pregnancy: final report.

In a 7-year prospective study cytomegalovirus (CMV) was shown to infect approximately twice as many pregnant women as did rubella virus. Fetal loss occurred in 4/26 (15%) early CMV infections which was seven-fold higher than the rate found in controls (16/744; 2.2%). There was no evidence that fetal loss resulted from intrauterine transmission of virus. Fifty-eight women experienced primary CMV infection and congenital infection was found in nine (20%) of the 46 infants from whom clinical samples were obtained. Transmission of virus was found in 20%, 0% and 40% in the first, second and third trimesters respectively. All babies were normal at birth but two have so far developed definite intellectual impairment attributable to cytomegalovirus infection. The mothers of both of these cases were infected after the fetus had become legally viable. We conclude that the lessons learned from studying rubella infection during pregnancy cannot be applied to cytomegalovirus; in particular, we could find no evidence that termination of pregnancy should be offered to women with early CMV infections.

Abortion, Spontaneous↗
PubMed1983

Is pregnancy immunosuppressive? Humoral immunity against viruses.

Serum samples were obtained during the first trimester, second trimester, third trimester, at delivery and 6 weeks postpartum from each of 50 pregnant women. All 250 sera were tested for their content of antibodies specific for herpes simplex, measles, rubella and influenza A viruses. The geometric mean titres of antiviral antibody were shown to decline by 18-48% between the times of booking and delivery, and to return to initial values by the end of the puerperium. By means of two-way analysis of variance, the major confounding variable of differences between individuals was identified and controlled for, so that the progression of pregnancy was shown significantly to decrease titres of antiviral antibody. After allowance was made for haemodilution, antibody levels against two viruses (herpes simplex, measles) still declined significantly while those for rubella and influenza viruses actually increased significantly, so that no consistent effect of pregnancy was demonstrable. We conclude that the declining titres of antiviral antibodies seen in pregnant women are predominantly a manifestation of haemodilution and discuss the reasons for believing that humoral immunity remains intact during pregnancy.

Antibodies, Viral↗
PubMed1982

Is post partum rubella vaccination worthwhile?

This study was designated to determine whether a program of screening for rubella antibodies during pregnancy, coupled with selective vaccination after delivery, could effectively increase herd immunity. One thousand women were studied when they returned for further antenatal care after having been screened, and possibly vaccinated, during an earlier pregnancy. Overall, the program was shown to be 83% effective since 108 women were truly seronegative in their initial pregnancies and 90 of them had been rendered immune by the time of their next pregnancy. The 18 failures of the program were attributed to the haemagglutination inhibition test employed (eight cases), failure to administer vaccine (seven cases) and true vaccine failures (three cases). Five pregnant women became infected with rubella virus during the study but all were in their initial pregnancies. All seronegative women were shown to follow the instruction not to become pregnant within three months of vaccination. We conclude that a program of screening for immunity, together with selective vaccination post partum, can significantly reduce both the number of susceptible women and the number who experience rubella infection during pregnancy. Such programs should be vigorously encouraged as a means of helping to prevent congenital rubella.

Antibodies, Viral↗