散发性戊型肝炎病毒感染的诊断

用基因工程重组的戊型肝炎病毒基因结构区第二码框架和第二读码框架具有免疫表位的嵌合抗原，建立了间接酶联免疫法，检测散发性急性肝炎病人血清中抗－ＨＥＶＩｇＧ和ＩｇＭ抗体。在４６例急性肝炎病人中出抗－ＨＥＶＩｇＧ抗体阳性７例，阳性率为１５．２２％，７例ＩｇＧ抗体阳性中，有５例ＩｇＭ抗体也阳性，占７１．４％。     

Effect of age on serum immunoglobulin G subclass antibody responses to inactivated influenza virus vaccine

We previously reported an age-associated impairment of serum immunoglobulin G (IgG) antibody responses to inactivated influenza virus vaccine. The present study extends these observations by examining the IgG subclass distribution of vaccine responses measured by enzyme linked immunosorbent assay in healthy adults aged <40 (young), 40–64 (middle-aged), and ?65 (elderly) years. Serological responses in all age groups showed antibodies that were predominantly IgG1 and secondarily IgGS. Influenza antigen-specific IgG4 titers did not change following vaccination, and antibodies of the IgG2 subclass were not detected in any serum specimens. Aging was associated with a significant impairment of IgG1, but not of IgGS, antibody production. Relative differences in the magnitude and frequency of response between IgG1 and IgGS subclasses, which were present in young and middle-aged adults (viz., IgG1 > IgGS), were less apparent in the elderly. This observation was confirmed in a second analysis of IgG subclass-specific responses in a separate cohort of elderly vaccinees. These results suggest that the age-related impairment of humoral responses to inactivated influenza virus vaccine is primarily accounted for by differences in IgG1 antibody production, and that IgGS antibodies make up a larger proportion of the overall serologic response in the elderly than they do in younger persons. © 1994 Wiley-Liss, Inc.     

Serological diagnostics of hepatitis E virus infection

Development of accurate diagnostic assays for the detection of serological markers of hepatitis E virus (HEV) infection remains challenging. In the course of nearly 20 years after the discovery of HEV, significant progress has been made in characterizing the antigenic structure of HEV proteins, engineering highly immunoreactive diagnostic antigens, and devising efficient serological assays. However, many outstanding issues related to sensitivity and specificity of these assays in clinical and epidemiological settings remain to be resolved. Complexity of antigenic composition, viral genetic heterogeneity and varying epidemiological patterns of hepatitis E in different parts of the world present challenges to the refinement of HEV serological diagnostic assays. Development of antigens specially designed for the identification of serological markers specific to acute infection and of IgG anti-HEV specific to the convalescent phase of infection would greatly facilitate accurate identification of active, recent and past HEV infections.     

Abnormal immunoglobulin G subclass production in response to keyhole limpet haemocyanin in atopic patients.

A proportion of patients with atopic dermatitis have elevated serum levels of IgG4. In order to investigate further this abnormality of IgG subclass production, atopic patients were immunized with the protein antigen keyhole limpet haemocyanin (KLH), and IgG subclass responses following primary and secondary immunization were analysed. In the primary response, titres of IgG1, 2 and 3 antibodies were lower in the atopic patients than in the controls. In contrast, titres of IgG4 were much higher for the patient group. In both patients and controls, the kinetics of IgG4 antibody production following the initial immunization with KLH showed a slow rise reaching a peak at 30 weeks. This time course indicated that the high IgG4 response was unlikely to be due to previous exposure of the patients to a cross-reacting antigen. A higher proportion of IgG4 was also seen in the atopic patients following secondary immunization; indeed, IgG4 was the major subclass in the secondary response in the patient group. In the controls, but not in the patients, titres of IgG4 anti-KLH correlated with total serum levels of IgG4, and some of the highest IgG4 antibody responses were detected in atopic patients whose serum IgG4 concentration was in the normal range. The results suggest that raised serum levels of IgG4 in atopy may reflect abnormal isotype regulation in response to protein antigens.     

Spectrum of hepatitis E virus infection in India

A solid phase enzyme linked immunosorbent assay (ELISA) that detects IgM and IgG to hepatitis E virus (HEV) was used to study seroepidemiology in 40 healthy subjects and 227 consecutive patients with liver diseases in an endemic area. Fifty-two of the liver diseases patients (22.9 percent) had acute hepatitis E. In contrast, none of the 40 healthy subjects were positive for IgM anti-HEV, validating the ELISA assay. Twenty-three of 25 (92%) patients with epidemic non-A, non-B hepatitis were confirmed as having acute hepatitis E. Only 1 of the 10 patients with sporadic, fulminant hepatic failuire of non-A, non-B, non-C etiology was positive for IgM anti-HEV. Five (31.2%) of the 16 patients with acute hepatitis in HBsAg carriers were positive for IgM anti-HEV. One patient with acute hepatitis B wascoinfected with acute hepatitis E. Acute hepatitis was a disease of the adult population, with peak attack rates in the second and third decades of life. This disease was seen in only 4 (16%) of the 25 patients with acute viral hepatitis occurring below 14 years of age. Cholestasis was predominant in 25% of patients, enzyme elevation was monophasic, and all patients had clinical and biochemical recovery from the disease. The data suggest that the majority of patients with acute sporadic non-A, non-B, non-C hepatitis in India have hepatitis E. However, fulminant hepatic failure to sporadic nature is rarely from hepatitis E. © 1994 Wiley-Liss, Inc.     

Ovalbumin-specific immunoglobulin G and subclass responses through the first 5 years of life in relation to duration of egg sensitization and the development of asthma

BACKGROUND: Egg sensitization, particularly persistent sensitization, is a risk factor for later asthma. However, little is known about accompanying IgG and subclass responses and how they might relate to asthmatic outcome. OBJECTIVE: To characterize hen's egg ovalbumin (OVA) IgG and subclass responses through the first 5 years of life in relation to duration of egg sensitization and later asthma. SUBJECTS and METHODS: The subjects (n=46) formed part of a larger cohort, born to atopic parents, who had been evaluated prospectively for the development of asthma. Egg sensitization was classified as transient (positive egg skin prick test at 1 year only) or persistent (positive skin test for at least 2 years). Plasma OVA IgG, IgG1 and IgG4 concentrations at birth (cord), 6 months, 1 and 5 years of age were measured by ELISA. RESULTS: The kinetics of OVA IgG and IgG1 responses, but not IgG4, differed between egg sensitized and non-egg sensitized (NES) children. Only persistently sensitized children had a rise in OVA IgG1 concentration through the first year of life, and at 1 year of age they had significantly higher OVA IgG and IgG1 than either transiently sensitized or NES children. High OVA IgG1 was associated with later asthma: at 1 year of age, OVA IgG1 greater than 14,500 U predicted asthma with a sensitivity 64% and specificity 74%. CONCLUSION: OVA IgG and subclass responses relate to the duration of egg sensitization. Measurement of OVA IgG1 concentration in infancy might offer a useful adjunct to identify those at an increased risk of asthma.     

Serum immunoglobulin G antibody subclass responses to respiratory syncytial virus F and G glycoproteins after primary infection

Because the immunoglobulin G (IgG) response to carbohydrate antigens is typically from the IgG2 subclass and the IgG response to protein antigens is typically from the IgG1 and sometimes the IgG3 subclass, two respiratory syncytial virus glycoproteins, F and G, which differ substantially in the amount of glycosylation, were used as antigens in an enzyme-linked immunosorbent assay to determine IgG subclass responses in 20 infants and young children with naturally acquired respiratory syncytial virus infection. Both glycoproteins elicited primarily IgG1 and IgG3 responses, indicating that the protein moieties of the glycoproteins may be immunodominant in this age group.     

Varying abilities of recombinant polypeptides from different regions of hepatitis E virus ORF2 and ORF3 to detect anti‐HEV immunoglobulin M

Following infection with hepatitis E virus (HEV), anti‐HEV immunoglobulin (Ig) M is thought to develop before anti‐HEV IgG and to be a better marker for differentiating between the acute and convalescent phases of infection. In order to select polypeptides for improved detection of anti‐HEV IgM, six and three overlapping polypeptides from open reading frames (ORFs) 2 and 3, respectively, of HEV genotypes 1 and 4 were expressed as fusion proteins in Escherichia coli. The reactivities of the polypeptides with anti‐HEV IgM were evaluated using immunoblotting and enzyme immunoassays (EIAs). The data indicated that polypeptides from the N‐terminus of ORF3 and middle region of ORF2 were weakly or not reactive with anti‐HEV IgM, while those from the remaining regions of ORF2 and ORF3 contained reactive epitopes. Anti‐HEV IgM against the N‐ or C‐terminus of ORF2 appeared earlier and disappeared faster than that against polypeptides from the C‐terminus of ORF3, based on serum samples from rhesus monkeys infected experimentally, and from patients infected naturally, with HEV. The N‐ and C‐terminal polypeptides from ORF2 complemented one another in detecting anti‐HEV IgM and EIA sensitivity was improved significantly with a combination of these polypeptides. The reactivities of ORF2 polypeptides from genotypes 1 and 4 were similar but that of ORF3 differed with sera from monkeys infected by the two genotypes. Thus, a combination of N‐ and C‐terminal polypeptides of ORF2 from one genotype may be effective in EIAs to detect anti‐HEV IgM. J. Med. Virol. 81:1052–1061, 2009. © 2009 Wiley‐Liss, Inc.     

Hepatitis E virus seroprevalence in acute viral hepatitis in a developed country confirmed by a supplemental assay

Hepatitis E virus (HEV) infection is prevalent among cases of acute viral hepatitis in young adults in developing countries. HEV infection is not restricted to endemic areas, but would appear to be worldwide in distribution. In order to document the incidence of HEV infection in acute hepatitis cases in a developed country, IgG and IgM anti-HEV antibodies and HEV RNA were tested in 101 Caucasian patients with acute viral hepatitis; 92 of these cases had markers of acute viral hepatitis other than HEV. Forty-seven (46.5%) cases had IgG anti-HEV; IgM anti-HEV and HEV viremia were not detected. As the incidence of anti-HEV was higher than would be expected, the possibility of the occurrence of false positive results was subsequently investigated. Supplemental antibody testing, using a broadly reactive epitope region, reduced the frequency of anti-HEV to 17%. Therefore, supplemental antibody testing confirms the hepatitis E virus seroprevalence in a developed country. Since IgM anti-HEV and HEV viremia were not detected, persons with IgG anti-HEV may be “subclinical HEV cases,” or have long-lived antibodies in their circulation. © 1996 Wiley-Liss, Inc.     

Serological evidence for hepatitis E virus infection in Israel

Israel is suspected to be endemic for hepatitis E virus (HEV) because of its geographic location and the large-scale immigration from endemic countries. Although no cases of local HEV infection have been diagnosed, a serological survey would provide indirect evidence for such infection. We examined sera from 1,416 healthy subjects, including 1,139 Jews from various regions of Israel and 277 Arabs, most of whom reside in the West Bank of the Jordan River. In addition, we tested 13 non-A, non-B, and non-C viral hepatitis patients. Sera were screened for antibody to hepatitis E virus (anti-HEV) by a newly developed enzyme immunoassay (EIA) and by immuno-blots for both IgG and IgM anti-HEV activity. Positive samples were confirmed by neutralization. The seroprevalence found by EIA was 2.81% and 1.81% in the Jewish and Arab populations, respectively. More than a 2-fold higher prevalence in males compared to females and an increase with age were found in both populations. However, these differences were nonsignificant. The geographical distribution was even throughout the country, except for two clusters of 3 and 4 seropositive individuals possibly reflecting past foci of infection. Eight of 37 ElA-positive sera were positive for IgG, and 3 were positive for IgM by the immunoblot assay. Among hepatitis patients (9 acute and 4 chronic), one patient with chronic hepatitis was positive for both IgG and IgM. Our study provides indirect evidence that Israel is endemic for HEV. The lack of outbreaks may be attributed to generally good hygienic conditions and a controlled potable water supply, while unrecognized sporadic cases may be due to the unavailability of diagnostic tests. © 1995 Wiley-Liss, Inc.     

The histology of acute autochthonous hepatitis E virus infection

AIM: To document the histological appearances of liver biopsies in autochthonous hepatitis E virus (HEV) infection. METHODS AND RESULTS: Four patients were serologically positive for HEV; three had no traditional risk factors, the fourth had recently returned from China. All four consumed meat products. Liver histology of the three autochthonous (locally acquired) cases showed portal tracts expanded by a severe mixed polymorph and lymphocytic inflammatory infiltrate, with a geographical distribution of polymorphs at the interface and lymphocytes centrally. Moderate to severe interface hepatitis and cholangiolitis were present. There was a striking acinar mixed inflammatory infiltrate made up of polymorphs, lymphocytes and macrophages; frequent apoptotic hepatocytes, focal necrosis, cholestatic rosettes and zone 3 canalicular and cytoplasmic bilirubinostasis were noted. Significant steatosis, megamitochondria and Mallory bodies were not present. There was no evidence of iron, copper or alpha(1)-antitrypsin accumulation. By contrast, the histology of the imported case of HEV infection showed less intense portal and acinar inflammation, no cholangiolitis and no geographical distribution of the portal inflammatory infiltrate. CONCLUSION: The histological appearances of autochthonous HEV infection are sufficiently distinctive to consider the diagnosis in an acute setting and possibly to differentiate it from the endemic form of the disease.     

Molecular virology of hepatitis E virus

This review details the molecular virology of the hepatitis E virus (HEV). While replicons and in vitro infection systems have recently become available, a lot of information on HEV has been generated through comparisons with better-studied positive-strand RNA viruses and through subgenomic expression of viral open reading frames. These models are now being verified with replicon and infection systems. We provide here the current knowledge on the HEV genome and its constituent proteins - ORF1, ORF2 and ORF3. Based on the available information, we also modify the existing model of the HEV life cycle.     

Efficacy of an accelerated vaccination schedule against hepatitis E virus infection in pregnant rabbits

An important goal of the Hepatitis E virus (HEV) vaccine is to prevent adverse pregnancy outcomes caused by different HEV genotypes during pregnancy, but studies directly evaluating maternal vaccination for HEV are lacking. Here we report maternal vaccination using HEV 239 vaccine in a pregnant rabbit model. Two dose of accelerated vaccination schedule (0, 7 days) induced high titers of anti-HEV protective antibodies in a short period of time in pregnant rabbits, which could protect the pregnant rabbits from HEV infection and adverse pregnancy outcomes. In addition, the immunized rabbits transfer maternal antibodies to pups through the placenta and breast milk, which protect neonates against HEV infection. Our results suggest that, besides vaccinating nonpregnant individuals, HEV 239 vaccine may also be discreetly considered for maternal vaccination.     

Immunoglobulin subclass distribution of specific antibodies in allergic patients

The IgG and IgA subclass distribution of specific antibodies against a variety of protein and polysaccharide antigens was determined in sera from individuals with high levels of IgE. No shift of the antibody pattern could be observed, suggesting that the aberrant regulation of responses against allergens noted in these patients is limited, encompassing selected antigens only. Antibodies against protein antigens are mainly of the IgG1 subclass. In addition, low levels of specific IgG3 or IgG4 antibodies may be formed. Our data suggest that a given antigen induces either IgG3 or IgG4 and that potential allergens, in addition to IgG1 and IgE, elicit a response restricted to IgG4.     

Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection

A newly developed assay for IgA class antibody to hepatitis E virus (IgA anti-HEV) was used to study 145 serum samples collected during an outbreak of an enterically transmitted hepatitis that occurred in 3 villages in the lower Shebeli region of Southern Somalia between January, 1988 and November, 1989. A total of 52.4% of the afflicted patients were found positive for IgA anti-HEV, and 73.1% of these were also positive for IgM. Both antibodies disappeared during the convalescence period. Similar results were also seen in serum obtained from sporadic cases of acute waterborne hepatitis in Pakistan. © 1993 Wiley-Liss, Inc.     

Anti-hepatitis B surface antigen IgG1 subclass is predominant in individuals who have recovered from hepatitis B virus infection, chronic carriers and vaccinees

Patterns of each IgG-specific subclass for hepatitis B virus (HBV) core antigen (anti-HBc) are remarkably different among individuals with different infection status, i.e., completely recovered or chronic carrier. Each of the IgG-specific subclasses of HBV surface antigen (anti-HBs) was tested for ELISA sensitivity using four commercially available hepatitis B surface antigen (HBsAg) kits and one self-prepared plate. The specificity in 18 serum samples obtained from chronic HBV carriers, recovered individuals, vaccinees and non-infected individuals was investigated. Differences in absorbance values were obtained by comparing results from these different plates. Data on the absorbance values of anti-HBs IgG subclasses obtained indicated that one to four subjects had a false-negative or false-positive result using the four commercial plates. Only the self-prepared plate demonstrated 100% specificity and sensitivity for anti-HBs subclasses. Moreover, the results indicate that anti-HBs subclass IgG1 was predominant in cured patients, chronic carriers and vaccinees. The samples from both chronic carriers and vaccinees exhibited a significantly higher concentration of total IgG and IgG1 than samples in recovered individuals (P<0.05).     

Locally acquired hepatitis E virus infection, El Paso, Texas

Hepatitis E virus (HEV) is an enterically transmitted RNA virus that causes both epidemic and sporadic cases of acute hepatitis. Despite sero-surveys showing antibody to HEV in up to 36% of the US population, acute hepatitis E has been reported among individuals with no history of international travel only three times in the United States. We report a case of apparently locally-acquired hepatitis E that occurred in El Paso, Texas that was 98% similar to a previously isolated HEV found in swine in the United States. Like the three previous cases, a thorough investigation found no conclusive sources of infection. Active case surveillance found no additional cases.     

Immunological and clinical profile of adult patients with selective immunoglobulin subclass deficiency: response to intravenous immunoglobulin therapy

Selective immunoglobulin (Ig)G3 subclass deficiency in adults, especially its immunological profile, has not been described previously in detail. Therefore, a retrospective chart review was conducted to characterize the immune profile and clinical manifestations in adult patients with selective IgG3 deficiency. We reviewed the charts of 17 adult patients attending our subspeciality immunology clinic with a diagnosis of selective IgG3 deficiency. The following immunological test results were recorded: lymphocyte subsets, proliferative response to mitogens (phytohaemagglutinin, concanavalin A, pokeweed mitogen) and soluble antigens (mumps, Candida albicans, tetanus toxoid), specific antibody response to tetanus toxoid and pneumococcal antigens, neutrophil oxidative burst and natural killer cell cytotoxicity. In addition, we recorded information about the types of infections and other associated diseases, and response to intravenous immunoglobulin therapy (IVIG). In the majority of patients, lymphocyte subsets were normal. Proliferative responses to mitogens and antigens were decreased in 33% and 40% of patients, respectively. Specific antibody responses to tetanus were normal; however, responses to various pneumococcal serotypes were impaired in a subset of patients. Patients suffered from recurrent upper respiratory tract infections, which usually decreased in frequency and severity following treatment with IVIG. The majority of these patients also had concurrent atopic diseases in the form of allergic rhinitis or asthma. Selective IgG3 subclass deficiency should be considered in adults with recurrent upper respiratory tract infections with or without allergic rhinitis or asthma, who may have normal levels of total IgG. IVIG appears to be an effective therapy.     

Seroprevalence of hepatitis E virus antibodies in different human populations of Cameroon

Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide. HEV infection is self-limiting, but fulminant hepatitis may occur with higher mortality rates. The aim of this study was to determine the seroprevalence of the HEV in three different populations in Cameroon and to assess alimentary risk factors of infection. A total of 903 individuals including 450 elderly people, 183 pregnant women, and 270 HIV-infected patients were enrolled during 2009-2015. All sera obtained were tested for the presence of anti-HEV antibodies with commercial enzyme-linked immunosorbent assay kits. The association between initial anti-HEV status and potential risk factors was assessed. Out of the 903 samples, 22.0% (199/903) were positives for anti-HEV immunoglobulin M (IgM), 5.8% (52/903) for anti-HEV IgG, and 3.5% (32/903) for both. The seropositivity for IgM was 7.0%, 13.1%, and 34.7%; meanwhile, the seropositivity for immunoglobulin G was 8.5%, 3.3%, and 5.1%, in HIV-infected patients, pregnant women, and the elderly population, respectively. Both antibodies were detected simultaneously in 2.2%, 1.6%, and 5.1% in HIV-infected patients, pregnant women, and the elderly population, respectively. No risk factors were significantly associated with HEV infection in these populations. This study showed a high prevalence of anti-HEV antibodies in three different populations in Cameroon.