A mucosal antibody response following systemic Haemophilus influenzae type B infection in children.

The possibility that mucosal antibody is produced as a host response to Haemophilus influenzae type b (Hib) infection was examined in this study. 17 of 18 prospectively evaluated children ranging in age from 2 mo to 7 yr developed a detectable level of anticapsular antibody in their nasopharyngeal secretions after systemic Hib infection. The mean concentration of nasal anti-capsular antibody of the 18 children was 554 ng/mg IgA (SD = 35-8,863) during the acute phase of illness and declined to 224 ng/mg IgA (SD = 19-2,688) in convalescence. Some children had mucosal antibody detectable at least 10 mo after infection. The mucosal antibody levels were not affected by the length of illness before diagnosis, type of disease, age of the patient, sex, or presence of detectable capsular antigen or viable bacteria in the nasopharynx. The mucosal antibody was predominantly of the IgA class and occurred independent of the serum antibody. Six of the children aged less than 1 yr who did not produce and/or sustain a serum antibody level correlated with protection demonstrated a persistent mucosal antibody response. These findings suggest that the mucosal immune system may have the ability to respond at an earlier age than the serum immune system and lead us to postulate that protective secretory antibodies to prevent systemic Hib disease may be inducible in young infants in spite of the poor serum antibody response occurring at this age.     

Anti-nucleoprotein antibody response in influenza A infection.

The nucleoprotein (NP) antigen isolated from influenza A virus by solubilization with Triton X-100 (TX-100) and further electrophoresis with SDS-cellulose acetate membrane gave a single band on SDS-polyacrylamide gel electrophoresis. Rabbit anti-serum hyperimmunized with the NP reacted only against the NP antigen. Moreover, a well-defined single precipitin line was shown between the NP and human sera. These results suggested that the NP was possible to detect anti-NP antibody in human serum. Immuno double diffusion (IDD) and single radial immunodiffusion (SRD) tests using the NP were established to detect the anti-NP antibody in human sera. During an epidemic caused by antigenic drift strain, anti-NP antibody was detected by the IDD test in the cases which did not show any significant rise in HAI titer. During a mixed epidemic caused by the different strain of HA antigen, the infection ratio in mass population was revealed more convenient and sensitive by SRD than HAI. The anti-NP antibody was detected by IDD for long periods of one year or more after infection. These results suggest that the detection of anti-NP antibody is applicable to serologic studies, particularly serologic diagnosis and serologic surveys of influenza infection in mass population.     

Hemagglutinin-specific complement-dependent antibody response to influenza infection

The host defense response to influenza infection is complex. Specific humoral antibodies develop to the strain-specific surface antigens, the hemagglutinin and the neuraminidase, and to the internal antigens (matrix and nucleoprotein) which are common to all influenza A viruses (1). Antibodies to the hemagglutinin, which is the major surface antigen, neutralize viral infectivity (2). In addition to antibodies which have been detected against virion antigens, a cytotoxic T-cell response with specificity against the viral hemagglutinin on influenza-infected target cells (3-5) has been recently described. A more cross-reactive cytotoxic T-cell response has also been observed when a nonpermissively infected target cell is used in cytotoxicity assays (6,7). The present report describes the development during influenza infection and after vaccination of a cytolytic humoral antibody response which is directed against the hemagglutinin on infected target cells. This antibody-mediated lysis of infected cells in complement dependent, as has been reported with other virus infections (8-11).     

The impact of biologic response modifiers on hepatitis B virus infection

INTRODUCTION: The biologic response modifiers are a diverse group of medications that have emerged over the last decade. They target pro-inflammatory cytokines or cell surface molecules that drive illnesses such as rheumatoid arthritis. Despite the greater control afforded they have also ushered in a new spectrum of side effects. As the same immunologic machinery that helps control infections such as HBV contributes to the pathogenesis of rheumatologic diseases, persistence or reactivation of the virus remains an evolving concern. AREAS COVERED: A systemic literature review was performed using the PubMed and Medline databases (1996 to January 2010) searching for the index term 'Hepatitis B' combined with the terms 'tumor necrosis factor', 'B cell', 'rituximab', 'IL-1', 'anakinra', 'IL-6', 'tocilizumab', 'CTLA-4', and 'abatacept'. All relevant articles in English were reviewed and secondary references of interest were also retrieved. This paper addresses the role of the various cytokines and cluster of differentiation molecules in controlling HBVinfection and the currently known effect that the biologic response modifiers have on viral control by the host immune response. EXPERT OPINION: The risk of HBV reactivation is greatest in HBsAg positive patients. These patients should start antiviral therapy one week before receiving a biologic response modifier. The risk of HBV reactivation in HBsAg negative patients appears very low but when HBsAb titers are low use of rituximab or TNF-α antagonists may increase the risk of reactivation.     

The impact of biologic response modifiers on hepatitis B virus infection

Introduction: The biologic response modifiers are a diverse group of medications that have emerged over the last decade. They target pro-inflammatory cytokines or cell surface molecules that drive illnesses such as rheumatoid arthritis. Despite the greater control afforded they have also ushered in a new spectrum of side effects. As the same immunologic machinery that helps control infections such as HBV contributes to the pathogenesis of rheumatologic diseases, persistence or reactivation of the virus remains an evolving concern.

Areas covered: A systemic literature review was performed using the PubMed and Medline databases (1996 to January 2010) searching for the index term ‘Hepatitis B’ combined with the terms ‘tumor necrosis factor’, ‘B cell’, ‘rituximab’, ‘IL-1’, ‘anakinra’, ‘IL-6’, ‘tocilizumab’, ‘CTLA-4’, and ‘abatacept’. All relevant articles in English were reviewed and secondary references of interest were also retrieved. This paper addresses the role of the various cytokines and cluster of differentiation molecules in controlling HBVinfection and the currently known effect that the biologic response modifiers have on viral control by the host immune response.

Expert opinion: The risk of HBV reactivation is greatest in HBsAg positive patients. These patients should start antiviral therapy one week before receiving a biologic response modifier. The risk of HBV reactivation in HBsAg negative patients appears very low but when HBsAb titers are low use of rituximab or TNF-α antagonists may increase the risk of reactivation.     

Dual infection with hepatitis B and C. Spontaneous course and response to virostatic therapy in children following neoplastic diseases

Combined chronic hepatitis B and C is a long-term complication in children surviving malignancy. We report on seven children who acquired hepatitis B as well as C virus infection during treatment for different malignancies. Four patients showed a spontaneous HBe Ag/anti-HBe seroconversion, two patients spontaneous clearance of hepatitis C virus, and one patient showed both HBe Ag/anti-HBe seroconversion and clearance of hepatitis C virus. One patient developed HBe Ag/anti-HBe seroconversion after antiviral interferon monotherapy and another patient after combination therapy with interferon/famcyclovir. Three patients developed complete sustained response of hepatitis C to a combined virostatic therapy with interferon and ribavirin. A total of 4 of 7 patients had a clearance of both infections and 3 of 7 patients had a clearance of at least one infection. CONCLUSION: Our data in long-term survivors of childhood cancer with combined hepatitis B and C showed a remarkably high rate of spontaneous cure and a favourable response to antiviral therapy.     

IgE antibody and resistance to infection. I. Selective suppression of the IgE antibody response in rats diminishes the resistance and the eosinophil response to Trichinella spiralis infection

Selective suppression of the total IgE antibody response has been achieved in rats by injection of rabbit anti-rat epsilon-chain antibodies. This IgE-specific suppression was maintained during the course of a natural infection by the nematode Trichinella spiralis. Depletion of the IgE antibody response resulted in a marked reduction of the number of eosinophils attracted to the T. spiralis larvae encysted in striated muscle. Blood eosinophilia following T. spiralis infection, although reaching normal peak levels, was abbreviated in IgE- suppressed animals. Moreover, IgE-depleted animals were more susceptible to the infection; they harbored two to three times more larvae encysted in their muscles than their control litter mates.     

The cellular basis for lack of antibody response to hepatitis B vaccine in humans

We had previously obtained evidence that among normal subjects the humoral antibody response to hepatitis B surface antigen (HBsAg) was bimodally distributed with about 14% of subjects producing less than 1,000 estimated radioimmunoassay RIA units. From the study of major histocompatibility complex (MHC) markers in the very poor responders who produced less than 36 estimated RIA units of antibody, it appeared that there was an excess of homozygotes for two extended haplotypes [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7]. This finding suggested that a poor response was inherited as a recessive trait requiring nonresponse genes for HBsAg on both MHC haplotypes and was strengthened by finding a much lower antibody response among prospectively immunized homozygotes for [HLA-B8, SC01, DR3] compared with heterozygotes. In the present study, we have analyzed the cellular basis for nonresponse to this antigen by examining antigen-specific proliferation of T cells from responders and nonresponders in the presence and absence of autologous CD8+ (suppressor) cells. Peripheral blood cells from nonresponders to HBsAg failed to undergo a proliferative response to recombinant HBsAg in vitro, whereas cells from responders proliferated vigorously. This failure of cells from nonresponders to proliferate was not reversed in cell mixtures containing CD4+ and antigen-presenting cells devoid of CD8+ cells. There was no difference between responders and nonresponders with respect to the number of circulating T cells or their subsets, or the proliferative response to mitogens such as pokeweed or phytohemagglutinin or another antigen, tetanus toxoid. Our results indicate that our HBsAg nonresponding subjects have a very specific failure in antigen presentation or the stimulation of T helper cells, or both. Our evidence is against specific immune suppression as the basis for their nonresponsiveness. The failure of antigen presentation or T cell help is consistent with recessive inheritance of nonresponsiveness and suggests that response is dominantly inherited.     

The fluorescent antibody method in the diagnosis of hepatitis B virus infection in glomerulonephritis patients

In 107 patients with glomerulonephritis (GN) (28 were with acute and 79 with chronic GN) and 54 patients afflicted with other diseases of the kidneys, peripheral blood leukocytes were examined for HBsAg by indirect immunofluorescence. In 60 patients with GN and 32 patients with other diseases, blood sera were examined for HBsAg and anti-HBs by enzyme immunoassay along with examination of blood leukocytes for HBsAg. In blood leukocytes of GN patients, HBsAg was detected in 23.4% of cases, whereas in patients afflicted with other diseases of the kidneys, in 5.6% of cases. In the blood serum, HBsAg was also demonstrated more frequently in GN patients (in 15% of cases) as compared to patients with other diseases of the kidneys (in 3.1% of cases). The rate of anti-HBs demonstration did not significantly differ in patients with GN and in those suffering from other diseases of the kidneys. None of the examined patients both with GN and other diseases of the kidneys showed at a time HBsAg and anti-HBs in the serum or HBsAg in leukocytes and anti-HBs in the blood serum. HBsAg in leukocytes and in the blood serum was identified at a time only in one patient afflicted with chronic GN.     

Effect of nonprotective vaccination on antibody response to subsequent human immunodeficiency virus infection.

We have investigated the systemic anti-HIV antibody response in chimpanzees who were immunized with live vaccinia containing either the HIV envelope glycoprotein (gp160IIIB) or a control antigen (herpes simplex virus glycoprotein D) and then challenged with either a high dose (300,000 TCID50) or low dose (100 TCID50) of HIVIIIB. HIV was subsequently isolated from all animals, indicating failure of the vaccination to protect against HIV infection. Serum antibody responses were evaluated before immunization, at the time of challenge with HIV, and at multiple time points in the 9 mo after challenge. Immunization resulted in a more rapid rise of antibody to gp160 in both high and low dose animals. Antibodies to the V3 loop induced upon infection were unaffected by immunization. In low dose animals, neutralizing antibody rose more rapidly and to higher levels in the immunized animals as compared with the control. There was no difference in neutralizing antibodies between immunized and control chimpanzees in the high dose group. Epitope mapping of the anti-gp 160 response indicated that immunization with gp160 vaccinia induced a postinfection antibody response to a region of gp41 (amino acids 718-743) that was not immunogenic in control-vaccinated animals. These data indicate that failed vaccination with the HIV envelope can alter both the timing and epitope specificity of the subsequent anti-HIV antibody response. These studies also define the evolution and fine specificity of the antibody response during the critical period immediately postinfection.     

The serology of chronic hepatitis B infection revisited.

The serology of chronic hepatitis B infection has been established through the use of commercial immunoassays to measure the structural antigens of the hepatitis B virus and their respective antibodies in serum. However, the commercial assays have not been designed to detect serum antibodies in the presence of an excess of circulating antigens. A series of serum samples from 200 HBeAg-positive, chronically infected hepatitis B patients with varying degrees of liver disease were analyzed using novel immunoassays designed to detect antibodies in the presence of circulating viral antigens. All patients, regardless of their liver disease, were seronegative for antibodies specific for the envelope antigens or the secreted nucleoprotein antigen (HBeAg) when the commercial assays were used. In contrast, virtually all chronically infected patients with liver disease and approximately 50% of patients without liver disease demonstrated anti-HBe and anti-envelope antibodies when sera were tested in the more sensitive immunoassays. Furthermore, asymptomatic patients could be serologically distinguished from symptomatic patients based on antibody fine specificity, titer, and IgG subclass. This study revealed that the majority of chronically infected hepatitis B patients produce a variety of antibodies for many years, and are not immunologically unresponsive, as suggested by the current assays.     

急性甲型肝炎病毒感染儿童总IgE抗体及Th17相关细胞因子变化研究

目的探讨甲型肝炎病毒(HAV)感染对儿童过敏性疾病的影响及HAV感染过程中Th17所起作用。方法收集2014年6月至2015年6月该院收治的41例急性HAV感染儿童及41例健康对照儿童详细临床资料进行回顾性分析,应用ELISA方法检测血清总IgE及Th17相关细胞因子水平。结果急性HAV感染儿童血清中总IgE水平低于健康对照组(P0.05),且随肝脏损伤程度增加IgE水平进一步减少;急性HAV感染儿童Th17相关细胞因子水平高于健康对照组(P0.05);IgE抗体和IL-17水平呈负相关(r=-0.533,P0.05)。结论急性HAV感染儿童Th17相关细胞因子水平显著升高,可能通过减少IgE水平介导对抗过敏反应的发生。     

Immune response to B19 parvovirus and an antibody defect in persistent viral infection.

B19 parvovirus has been shown to persist in some immunocompromised patients, and treatment with specific antibodies can lead to decreased quantities of circulating virus and hematologic improvement. A defective immune response to B19 parvovirus in these patients was shown by comparison of results using a capture RIA and immunoblotting. In normal individuals, examination of paired sera showed that the dominant humoral immune response during early convalescence was to the virus major capsid protein (58 kD) and during late convalescence to the minor capsid species (83 kD). In patients with persistent parvovirus infection, variable titers against intact particles were detected by RIA, but the sera from these patients had minimal or no IgG to capsid proteins determined by Western analysis. Competition experiments suggested that this discrepancy was not explicable on the basis of immune complex formation alone and that these patients may have a qualitative abnormality in antibody binding to virus. In neutralization experiments, in which erythroid colony formation in vitro was used as an assay of parvovirus activity, sera from patients with poor reactivity on immunoblotting were also inadequate in inhibiting viral infectivity. A cellular response to purified B19 parvovirus could not be demonstrated using proliferation assays and PBMC from individuals with serologic evidence of exposure to virus. These results suggest that production of neutralizing antibody to capsid protein plays a major role in limiting parvovirus infection in man.     

Effective antibody therapy in herpes simplex virus ocular infection. Characterization of recipient immune response

The immunotherapeutic potential of a monoclonal antibody specific for glycoprotein D of herpes simplex virus was evaluated in a murine ocular infection model. Passive transfer of antibody at microgram concentrations was able to promote resolution of corneal opacity and hasten healing of blepharitis. Antibody treatment did not prevent development of either a cellular or humoral antiviral immune response. In fact, kinetic studies revealed that the early delayed-type hypersensitivity response was significantly more vigorous in the treated group than in the controls. Potential explanations as to how a single microgram inoculation of antibody could exert a therapeutic effect are discussed.     

Treatment of hepatitis C infection.

There is growing awareness of the health risk posed by hepatitis C virus and fears that an epidemic of 'AIDS proportions' may be just around the corner. As our understanding of the disease increases, it is likely that substantial resources will be spent on developing newer and more effective treatments for hepatitis C infection in the years ahead.     

Donor screening for antibody to hepatitis B core antigen and hepatitis B virus infection in transfusion recipients

BACKGROUND: Testing for antibody to hepatitis B core antigen (anti-HBc) as a surrogate for hepatitis C viremia is no longer needed for blood donor screening. Currently, the important question is how much its use supplements hepatitis B surface antigen (HBsAg) donor screening in preventing transfusion-transmitted hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In a study conducted in the 1970s, 64 blood donors were associated with 15 cases of HBV (1.0%) in 1533 transfusion recipients. Sera from 61 donors at donation and 29 follow-up visits were available for present-day assays for HBsAg, HBV DNA, anti-HBc, and antibody to HBsAg (anti-HBs). RESULTS: HBsAg was found in four previously negative blood donors; HBV DNA was limited to three of these four. Anti-HBc was detected in six HBsAg-negative donors. Two other donors were negative in all assays at donation, but positive for anti- HBc and anti-HBs 2 to 4 months later. The remaining donors were negative for all HBV markers, which left five recipient cases unexplained. No HBV transmission was observed when anti-HBs sample-to- negative control values were > or = 10. CONCLUSION: Some 33 to 50 percent of cases of hepatitis B that could be transmitted by transfusion of blood from HBsAg-negative donors are prevented by anti- HBc screening. Anti-HBc-positive donors unequivocally positive for anti- HBs should be considered noninfectious for HBV and should be allowed to donate. Anti-HBc screening of paid plasmapheresis donors, supplemented by anti-HBs testing, would reduce the amount of HBV to be processed by virus inactivation and increase the content of anti-HBs in plasma pools.     

Long-term persistence of antibody following immunization of healthcare workers with hepatitis B vaccines

A group of healthcare workers (HCW) was immunized with hepatitis B vaccine. The serum-derived vaccine was used between 1984 and 1987. Since 1987, two types of recombinant vaccines were used. Antibody response occurred in 92.2–96.2% of HCW who were immunized. For the serum-derived vaccine group, antibody persisted for up to 9 yr of follow-up. For the recombinant vaccine groups, antibody persisted during the follow-up period of up to 6 yr.