Mother-to-infant transmission of HIV.
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Biomedical subjects
Publications and source records attributed to B Wahren.
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Serum PLAP/PLAP-like enzymes are elevated in testicular cancer patients and also in heavy smokers. Such elevations were measurable with anti-PLAP polyclonal and monoclonal antibodies, and an antigenic heterogeneity was demonstrated in the circulating enzymes. Thus polyclonal antibody revealed more of tumor PLAP-like antigen while a monoclonal antibody H7 detected PLAP of smokers better. PLAP of smokers and PLAP-like enzyme of cancer (seminoma) patients showed similar characteristics with respect to glycosylation pattern, charge and hydrophobicity. By these properties they were differentiated from PLAP of placenta.
Tumor marker identification in testicular cancer has contributed to early detection and monitoring of non-seminomatous disease. A placental alkaline phosphatase-like (PLAP-like) enzyme derived from seminomas has recently been focused upon as a possible marker for this disease. The biochemistry of the PLAP-like enzyme is reviewed, as well as its occurrence in tissue and sera from healthy persons and patients with testicular cancer.
ELISAs utilizing HIV-derived synthetic peptides as antigen were used to analyze serum and CSF IgG1-4 from 15 HIV infected patients. Intrathecally synthesized IgG1-4 reactive to one or several HIV-derived peptides were detectable in 12 of 15 patients. Intrathecally synthesized anti-peptide IgG was more common in patients with neurological symptoms than in those without. CSF reactivity not paralleled by serum reactivity was detected to HIV-peptides in 4 patients. IgG1-4 to gp41 was relatively more frequent in the CNS than IgG1-4 to gag. Intrathecal IgG synthesis to the gp120 peptide was not detected in any patient. The anti-peptide responses were dominated by IgG1. Intrathecal IgG2 and 4 synthesis was found in 2 and 5 patients, respectively. IgG3 synthesis intrathecally was not detected in any of the patients. ELISAs detecting IgG1-4 to HIV-derived synthetic peptides are feasible to analyze the fine specificities of intrathecal IgG. The mapping of idiotypes and isotypes of IgG synthesized in the CNS will increase the possibilities of elucidating B-cell regulation in the CNS and which viral components evoke immune responses.
A new type of immunochemical mapping of the human immunodeficiency virus type 1 (HIV-1) gag region was performed. By use of native HIV-1 viral lysates or the gag recombinant p24-15 antigen, a new set of monoclonal antibodies (Mabs) to the gag region proteins was generated. Synthetic HIV-1 peptides covering the entire gag region were used to specifically localize the continuous epitopes by direct binding to the Mabs and by blocking the Mab immunoreactivity. The identified immunogenic epitopes were localized between the gag amino acids (aa) 108-127, 203-217, 208-222, 248-282, 273-302, 288-307, 308-322, 331-354 and 408-422. These continuous epitopes formed seven immunogenic regions. One strongly p17-reactive Mab appeared to react with a discontinuous epitope, the components of which were 110 aa distant in the linear sequence: aa 23-27 and 128-132. The synthetic peptides appeared to be more congruent with the Mab-reactive sites in solution than when coated to a solid phase.
The thymidine analogue 3'-azido-3'-deoxythymidine is an effective inhibitor of HIV replication in vitro and is used in the treatment of acquired immunodeficiency syndrome. We report here upon a rapid sensitive radioimmunoassay for the detection of azidothymidine in serum or plasma. The assay is simple to perform and levels as low as 1 ng azidothymidine/ml can be detected. The assay is specific for azidothymidine and shows almost no cross-reaction with closely related nucleoside analogues or with naturally occurring nucleosides. Using this radioimmunoassay we were able to measure the azidothymidine levels in the serum of monkeys and acquired immunodeficiency syndrome patients treated with AZT. Individual variation in the peak serum level and clearance rate of azidothymidine were seen, which emphasizes the need to tailor the dose to the individual.
An indirect enzyme-linked immunosorbent assay (ELISA) with human herpes virus 6 (HHV6) membrane antigen was compared with indirect immunofluorescence assay (IFA) for measurement of HHV6 IgG antibodies. Five hundred serum samples from 403 Swedish patients with suspected symptomatic Epstein-Barr virus (EBV) infections were examined. The specificity of the ELISA compared with IFA was 98.7% and the sensitivity was 98.4%. In 90% of the patients, IgG antibodies to HHV6 were detected with both assays. The highest HHV6 IgG titers were found mainly in patients with EBV or CMV infections, but HHV6 mononucleosis was not diagnosed. The same HHV6 antigen was assessed for IgM ELISA but was found to be of limited value due to high IgM reactivity with the control antigen. The HHV6 IgM ELISA requires further investigation. The IgG ELISA described is a reliable alternative to IFA for measurement of HHV6 IgG antibodies and for large scale epidemiological studies.
In children born to human immunodeficiency virus (HIV)-infected mothers, factors that determine disease outcome and progression are unclear. Also, early diagnosis is hampered by maternally transferred antibodies. Children aged 0-24 months were retrospectively divided into two groups based on HIV seroreactivity or nonreactivity at age 15 months and analyzed for the presence of antibodies that mediate cellular cytotoxicity (ADCC) and virus neutralization. No difference was seen in the presence of these functional antibodies between groups. The persistently seropositive group was further divided into non-AIDS and AIDS groups according to clinical status at serum collection. The ADCC antibody frequencies were much higher (70%) in the non-AIDS group than in the AIDS group (30%). Of the non-AIDS children, 63% had neutralizing antibodies; no children with AIDS had these antibodies. HIV-specific ADCC and neutralizing antibodies do not seem to protect against transmission of HIV from mother to child but are significantly correlated with a better clinical stage of childhood HIV infection.
To diagnose infectious mononucleosis caused by Epstein-Barr virus (EBV), a peptide from the EBV nuclear antigen (EBNA) 1 (p107) and an EBNA 2 peptide (polyproline) were used as antigens in enzyme-linked immunosorbent assays for IgG and IgM. Well-characterized serum samples (360) from healthy individuals and patients with EBV or cytomegalovirus infections were examined. The p107 IgG and IgM assays were also tested with serum from 1000 patients with suspected EBV-related disorders. The p107 and polyproline IgG assays were 100% specific for EBV seropositivity. Low p107 IgG titers (less than 1000) were found in 98% of patients with EBV infectious mononucleosis but also in 18% of patients with other diseases. A p107-to-polyproline IgG ratio of less than 1 was 98% specific for EBV infectious mononucleosis; sensitivity was 86%. In EBV capsid antigen-IgG seropositive patients, a p107 IgG titer of less than 1000 together with a p107 IgG-to-IgM ratio of less than 1 was 98% sensitive and specific for EBV infectious mononucleosis. Thus, this ratio appears adequate to measure EBNA antibodies for diagnosis of EBV mononucleosis.
Amino acid sequences inducing neutralizing antibodies to HIV-1 were sought. Murine monoclonal antibodies (MAbs) were characterized by their reactivity with the envelope precursor gp160 or the Escherichia coli recombinant DNA products pB1 and pE3 representing the carboxy- and amino-terminal halves of mature envelope gp120. Fine mapping of the MAb determinants was performed using defined 15-mer synthetic peptides spanning the entire envelope gp120 region of HIV-1. One group of MAbs recognizes epitopes (amino acids 304-323) occurring in a small region with variable and conserved amino acid sequences of gp120. These MAbs mediate neutralization of the HIV-1 strain HTLV-IIIB (HIV-1IIIB) which was used for immunization. Nine out of 11 primary HIV-1 isolates were neutralized well or moderately well. In addition, prominent serological reactivity was noted with peptide sequences of strains of various European or American origins, but not with two HIV-1 strains of African origin. The cross-reactivity contrasts with previously described type-specific reactions to other sequences of this region. The reactivity to the short conserved site GPGR with its flanking amino acids may explain the broad sequence cross-reactivity seen with our neutralizing MAbs. Two other MAbs recognize conserved epitopes (amino acids 79-103) situated in the amino-terminal region of gp120. These MAbs did not neutralize HIV-1IIIB.
Sera from healthy seropositive donors, patients with acute measles, subacute sclerosing panencephalitis, common variable immunodeficiency, and CH gene deletions were analysed for anti-measles IgG1-4. Compared with other anti-viral immune responses of IgG1 and IgG3, an unusual predominance of specific IgG1 prevailed; only four out of a total of 68 patients showed anti-measles IgG3. Of the 17 healthy, measles seropositive serum donors, all showed specific IgG1, none showed IgG3 and six had IgG4. Eight out of 10 patients with SSPE showed an anti-measles IgG1 and IgG4 response while IgG3 was not seen. The IgG1 and IgG4 subclass patterns had some exceptions. Anti-measles IgG3 was found in five out of five patients with deletion of the gamma-1 encoding gene segments and in four out of 15 patients with recent measles antigen stimulation. The subclass pattern was suggested to reflect the immunological compromise associated with measles infections.
Cerebrospinal fluid, peripheral blood lymphocytes (PBL) and sera from 5 patients with herpes simplex encephalitis (HSVE), 3 with varicellae zoster (VZV) meningoencephalitis and 5 with encephalitis of unknown origin (NUD) were analyzed. Lymphocytes from both blood and CSF were shown to synthesize anti-VZV IgG subclasses in VZV meningoencephalitis and anti-HSV IgG subclasses in HSVE. The subclass patterns of CSF and in vitro synthesized anti-viral IgG were similar, suggesting that a considerable portion of the antiviral IgG subclasses detected are synthesized in the CNS compartment. Antigen presentation in vitro seemed to produce a heterologous IgG4 and/or 3 response in 3 patients. Lymphocyte proliferation was detectable in response to HSV and VZV, respectively.
Placental alkaline phosphatase (the PLAP-like isoenzyme) and liver alkaline phosphatase (LAP) were demonstrated immunohistochemically by use of monoclonal antibodies in the tumor cells of twelve seminomas and one seminoma metastasis. Intestinal alkaline phosphatase (IAP) was not found. The PLAP-like and LAP enzymes showed high catalytic activities compared to normal testis. This is the first occasion that LAP has been demonstrated by immunochemistry in seminoma cells. The results suggest that demonstration of these tumor enzymes may be useful markers for seminomas in histopathological specimens.
The in vitro susceptibilities of human herpesvirus 6 to foscarnet; the guanosine analogs acyclovir, ganciclovir, and two isomers of 9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine; and the thymidine analogs 3'-azido-3'-deoxythymidine and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil were investigated. All compounds except 3'-azido-3'-deoxythymidine and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil inhibited human herpesvirus 6 replication. The highest in vitro selectivity was obtained for 9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine.
Immunoglobulin G antibody titers to human herpesvirus 6 (HHV-6), measles virus, and cytomegalovirus (CMV) were examined in serum samples from 31 patients with Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM). Sera were drawn sequentially from the same patients less than or equal to 7 days until 3 years after onset of IM. In seropositive patients, there was a significant decrease with time after IM of the immunoglobulin G titers to the three viruses in the majority of patients; HHV-6 IgG titers decreased in 80%, measles virus IgG titers decreased in 75%, and CMV IgG titers decreased in 67%. Four patients contracted CMV infection during the observation period after IM. In these, HHV-6 IgG titers increased, while EBV and measles virus IgG titers remained essentially stationary. Polyclonal B-cell stimulation during IM is suggested to augment antiviral titers in general, but the increases of HHV-6 IgG titers during EBV and CMV infections may also be due to selective stimulation of memory B cells by related antigens or to reactivation of HHV-6 during infection with these herpesviruses.
Monoclonal antibodies (MAbs) were raised against human immunodeficiency virus type 1 gp120. One MAb, P4/D10, was found to mediate highly efficient antibody-dependent cellular cytotoxicity and virus neutralization. The reactivity was located to a major neutralizing region (amino acids 304 to 323) on gp120. Five other MAbs with a similar epitopic reactivity did not show any antibody-dependent cellulan cytotoxicity activity but had a virus-neutralizing capacity.
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The IgG subclass distribution to the E34/E32 peptides, derived from the HIV-1 glycoprotein 41 transmembrane protein, was analyzed in ELISA. Sera from individuals at different stages of the disease were assayed. A restricted subclass response of mainly IgG1 and IgG2 was found. The subclass response was of a different type than the one observed to HIV whole Ag and to a synthetic peptide from the C'-terminal part of the HIV-1 p24 core protein. An increased subclass restriction was observed in progressed stages of the disease.