IgM Seroconversion Research Articles

Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by Lactobacillus casei GG

In a search for new strategies to improve oral vaccination, the effect of orally administered Lactobacillus casei strain GG (LGG) in conjunction with D x RRV rhesus-human reassortant live oral rotavirus vaccine was tested in 2–5-month-old infants. Infants who received LGG showed an increased response with regard to rotavirus-specific IgM secreting cells, measured using an ELISPOT technique, on day 8 after vaccination. In infants receiving LGG or placebo, respectively, a rotavirus IgM seroconversion was detected in 26 27 (96%) versus 23 27 (85%) cases ( p=0.15) and rotavirus IgA seroconversion was detected in 26 28 (93%) versus 20 27 (74%) cases ( p=0.05). These findings suggest that LGG has an immunostimulating effect on oral rotavirus vaccination. The clinical significance of LGG-enhanced immune responses to oral vaccines should be further evaluated.

Hepatitis A Virus Infection among the Hemophilia Population at the Bonn Hemophilia Center

Following a publication on the sudden outbreak of hepatitis A (HAV) infections in Italian hemophiliacs after treatment with a solvent detergent (S/D) virus-inactivated factor VIII concentrate, we retrospectively examined our patients for HAV seroconversions and clinical symptoms of an acute HAV infection at our center. We found that between 1988 and 1992, 17 hemophilia A patients displayed HAV IgG seroconversions. Of these patients, 13 also had an HAV IgM seroconversion and 10 exhibited clinical symptoms of an acute HAV infection. A feature common to all was the fact that in the months prior to seroconversion they had been treated exclusively with the S/D-virus-inactivated product Octavi manufactured by Octapharma in Düsseldorf (FRG). None of the hemophilia A patients who had been treated with other products and who were susceptible to hepatitis A displayed seroconversion in the above-mentioned time span.

Elimination of circulatory IgM anti-HSA precedes anti-HBe seroconversion in patients with CAH type B.

The presence of IgM and IgA antibodies with specificity for human serum albumin (HSA) were consecutively analyzed in serum samples from four patients with biopsy verified CAH type B during seroconversion in the HBe/anti-HBe antigen system. Circulatory IgM anti-HSA antibodies were present during HBe antigenemia. The antibody titers fluctuated, decreased, and were finally lost from the circulation. After the disappearance of IgM anti-HSA antibodies, seroconversion to anti-HBe reactivity occurred and a quiescent phase of the disease was established, as judged by normalization of transaminases and absence of circulatory HBV-DNA. IgA anti-HSA antibodies persisted in the circulation after the elimination of IgM anti-HSA and seroconversion to anti-HBe reactivity. For one of the patients, a dramatic increase in titers was followed by elimination of IgA anti-HSA and seroconversion to anti-HBs. The data indicate that the host "self"-component HSA, when associated with "foreign" HBe or HBs antigenic structures, elicit immune responses to HSA, preventing the adequate development of anti-HBe and anti-HBs. The cessation of anti-HSA reactivity, however, seemed to permit subsequent sensitization to HBe and HBs antigenic determinants, as detected by the presence of circulatory antibodies.

Brief report: Primary human herpesvirus 6 infection in a patient following liver transplantation from a seropositive donor

A virus, isolated from peripheral blood lymphocytes of a patient 23 days after liver transplantation, was identified by negative contrast and thin-section electron microscopy, DNA hybridisation, and immunofluorescence as human herpesvirus 6 (HHV-6). The patient was seronegative for antibodies to HHV-6 before receiving the liver from a seropositive donor. Seroconversion for IgM and IgG antibodies occurred at the same time as the viraemia, indicating a primary response to HHV-6 infection that was probably acquired from the donor liver. The relationship of the infection to the patient's subsequent disease episodes is discussed.

IgM antibody to hepatitis B core antigen in children with chronic type B hepatitis.

IgM antibody to hepatitis B core antigen (anti-HBc IgM) was investigated by an antibody-capture radioimmunoassay (serum dilution 1:4000) in serum samples from 31 untreated children with chronic hepatitis B who were followed prospectively for 1-7 years. At the start, all patients were positive for hepatitis B e antigen (HBeAg), and anti-HBc IgM was detected in 23 cases, including 15 out of 16 with chronic active hepatitis and 7 out of 14 with chronic persistent hepatitis. A significant positive correlation was found between anti-HBc IgM levels and severity of liver damage (P less than 0.05), while an inverse relationship was found between anti-HBc IgM levels and distribution of hepatitis B core (HBcAg) antigen in the liver as detected by immunofluorescence. In fact 75% of anti-HBc IgM positive patients showed a focal HBcAg pattern (less than 40% positive nuclei), whereas 87% of antibody negative cases exhibited a diffuse HBcAg expression (more than 60% stained nuclei). During follow-up, seroconversion from HBeAg to anti-HBe with subsequent remission of liver disease occurred in 82% of patients presenting with detectable levels of anti-HBc, including three out of seven cases with chronic persistent hepatitis, but in none of the cases that were initially negative (P less than 0.01). These results indicate that during the natural course of chronic hepatitis B in children, anti-HBc IgM levels in serum reflect the degree of host immune response to infected hepatocytes. The close correlation between anti-HBc IgM seropositivity and seroconversion from HBeAg to anti-HBe suggests that anti HBc IgM may have a prognostic value during the follow-up of children with chronic HBeAg positive hepatitis B.

SEROLOGICAL RESPONSE TO THE HEPATITIS DELTA VIRUS IN HEPATITIS D

Sera from 74 hepatitis B surface antigen-positive individuals, who presented with acute hepatitis delta virus (HDV) infection which ran a self-limited course in 58 and progressed to chronicity in 16, were tested over time for HDV markers. In self-limited disease the serum pattern varied from early HD-antigenaemia followed by IgM and IgG anti-HD seroconversion, to the appearance of IgM and IgG anti-HD without antigenaemia , or the isolated expression of either the IgM or the IgG antibody. The typical case of IgM anti-HD was transient and appeared with a mean delay of 10-15 days from admission in the different serological subgroups. The IgG antibody usually developed several weeks later during convalescence. In contrast, patients with disease destined to become chronic had a brisk IgM antibody response and IgG anti-HD was detectable with a mean delay of 15 days; generally, the IgM and the IgG antibody persisted over the follow-up time. IgM antibody to HDV is often the only serological test positive in the clinical stage of hepatitis D and repeated testing for this marker is necessary to diagnose acute HDV co-infection. The serological follow-up provides important prognostic information: waning of IgM confirms resolution of HDV infection, persistence predicts chronicity.

Humoral antibody response of rabbits to experimental infection with Encephalitozoon cuniculi

Six female rabbits ( Oryctolagus cuniculus) were experimentally infected intravenously with approximately 1.5 × 10 7 live spores of Encephalitozoon cuniculi. Head tilt was observed as the single clinical sign in only one of the six animals. Antibody response was registered over 68 days postinfection using the indirect immunofluorescence test (IFT) for IgM and IgG, and the carbon immunoassay (CIA). IgG titers reached a level of 160–2560 after a latent phase of 13–28 days, followed by a 2–4 week relatively steep increase. The IgM seroconversion was faster than that of IgG and occurred at the beginning of the antibody response. Thus, simultaneous detection of both IgM and IgG allowed the infection to be identified as recent. Long, short, and episodic antibody responses could be distinguished: the IgG titer continued to increase on Day 68 in one animal (long response) and began to decrease between Days 45 and 63 in three other animals (short response). In two additional animals the seroconversion was very short, occuring between Days 13 and 41, and 28 and 52, respectively (episodic response). The CIA proved to be specific, reliable, and simple to perform; titers were slightly higher than in the IFT. Parasite pseudocysts were detected scattered throughout the brain on Day 68 in four of the six rabbits. The persistence of antigen in the brain did not correlate with antibody response, which in most cases was shorter.

Measurement of heterophil antibody and antibodies to EB viral capsid antigen IgG and IgM in suspected cases of infectious mononucleosis.

The EBV IgG titres in acute and convalescent specimens from 97 cases of infectious mononucleosis were compared with titres from acute and convalescent sera from 96 students with illnesses resembling infectious mononucleosis but without heterophil antibody, EB IgM or EB IgG seroconversion; and also with titres from 91 healthy students known to have had EB IgG antibody for at least six months. These titres were related to the titre of the Research Standard A.66/235 for infectious mononucleosis serum prepared by the National Institute for Biological Standards and Control. Serial sera were tested for heterophil antibody and EBVCA specific IgG and IgM from 61 university students with infectious mononucleosis. The period of persistence of heterophil antibody and EBV IgM after illness was outlined from the results of the tests. Single sera from 406 patients in hospital or general practice sent to the diagnostic laboratory for heterophil antibody tests were also tested for EBV antibodies without prior knowledge of the heterophil antibody result. The close agreement between heterophil antibody and EBV IgM results is shown. False positive EB IgM results were correlated with the presence of rheumatoid factor.