Complement activation decreases the ability of HIV transmembrane envelope protein to bind to specific antibody.
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Animals↗
Biomedical subjects
E Ujhelyi
Publications and source records attributed to E Ujhelyi.
Virus neutralizing antibodies at different stages of the HIV disease: increased levels after azidothymidine treatment.
Specific HIV-1 neutralizing activity was measured in single serum samples obtained from 52 individuals suffering from different stage of HIV disease, as well as in serum samples collected during a four years follow up of other 13 HIV-1 seropositive persons, from whose seven developed AIDS. Three of these persons were treated with azidothymidine. In the former group of single serum specimens, the specific neutralizing antibody positivity rate was 81 per cent in symptomless persons, 92 per cent in patients with ARC and 43 per cent in patients with AIDS. From 13 HIV-1 infected individuals, prospectively investigated from 1986 to 1990, six remained asymptomatic and no significant fluctuation of specific virus neutralizing antibody levels was noted. During this time period, remaining seven patients developed AIDS. In the sera of AIDS patients, specific neutralizing activity was either not detected or its titres were rather low before the appearance of clinical disease. Three AIDS patients were administered azidothymidine. Specific neutralizing antibody titres increased significantly one month after the beginning of azidothymidine administration and persisted at relatively high levels over several months of follow up.
AIDS-Related Complex↗
Prevalence and specificity of lymphocytotoxic antibodies in different stages of HIV infection.
Sera obtained from 27 HIV-infected persons were investigated for complement-dependent humoral cytotoxicity. Uninfected as well as HTLV-IIIB-infected H9 cells were used as cellular targets either before or after stimulation by phytohemagglutinin (PHA) or concanavalin A (Con-A). The degree of cytotoxicity was determined by 51Cr-release assay. Two different antibodies could be found in sera of HIV-infected persons, one being directed against HIV-induced cell surface component(s) and the other reacting with structure(s) present on activated T4 cells. Asymptomatic HIV-carries were found to have antibodies exerting complement-dependent cytotoxicity to HIV-infected T4 cells. These antibodies were reactive mainly after stimulation of HIV-infected target cells by Con-A. Sera of ARC and AIDS patients contained autoantibodies reactive with PHA-stimulated or HIV-infected T4 lymphocytes. These data suggest that HIV-specific antibodies represent an anti-viral immune defense, while autoantibodies may be important in destruction of the immune system in AIDS.
AIDS-Related Complex↗
Correlation of the percentage of activated, CD3 + DR + lymphocytes to serum neopterin level in HIV-seropositive haemophiliacs.
The percentage of activated, CD3+ DR+ and CD8+ Leu7+ lymphocytes and the serum neopterin concentration were determined in 17 HIV-seropositive and 10 HIV-seronegative haemophiliacs and in 11 healthy control subjects. All three parameters tested were found to be significantly higher in the seropositive patients than in the seronegative controls. In the seropositive group, a significant positive correlation was found between the neopterin levels and the percentage of CD3+ DR+ cells. By contrast, no significant negative or positive correlation was observed between the neopterin levels and the percentage of the CD8+ Leu7+ subset. These data suggest that in the HIV-infected patients the activated T cells responsible for the stimulation of macrophages to produce neopterin are those that do not carry CD8.
Adolescent↗
Neutralizing and complement-dependent enhancing antibodies in different stages of HIV infection.
Reclustering and indirect immunofluorescence assays on MT-4 cells [carrying both CD4 and complement receptor type 2 (CR2)] were used to measure neutralizing and enhancing antibodies in sera obtained from HIV-1-infected individuals. Heat-inactivated sera were tested before and after mixing 1:1 with fresh seronegative human serum. Using heated samples, neutralizing antibodies were found in 20 out of 20 and 11 out of 19 serum samples of asymptomatic and symptomatic [AIDS, AIDS-related complex (ARC)] HIV-seropositive patients, respectively. In complement-restored samples, neutralizing activity was found in eight sera of asymptomatic patients and in none of the sera of AIDS and ARC patients; enhancing activity could be detected in four and 12 sera, respectively. A significant positive correlation was observed between the titres of neutralizing antibodies measured in the complement-restored samples and the absolute number of CD4+ lymphocytes. These findings indicate that the appearance of complement-dependent enhancing antibodies coincident with the loss of neutralizing antibodies may indicate a poor prognosis in HIV infection.
AIDS-Related Complex↗
The complement system in HIV disease.
Different aspects of the relationship between the HIV infection and the complement system were studied. 1. No significant differences were found between seronegative controls, asymptomatic, and symptomatic (ARC, AIDS) HIV-seropositive patients in the plasma levels of complement components C4, Bf, and C3. 2. Using sensitive ELISA assays, a significant increase was observed in the levels of protein-protein complexes which are formed at the activation of the classical (C1r-C1s-C1-INH) and alternative (C3b-Bb-P) pathways, indicating that both complement pathways are activated in the HIV disease. No significant differences were found, however, in the levels of these complexes between the groups of asymptomatic and symptomatic HIV-infected patients. 3. Artificial immune complexes of synthetic peptides representing some immunodominant epitopes of HIV envelope (gp120, and gp41) proteins, and human polyclonal anti-HIV IgG were found to weakly activate both the classical and alternative complement pathways. 4. An elevated percentage of the lymphocytes carrying a complement activation fragment, C3d, was detected in the blood of HIV seropositive patients as compared to the seronegative controls. No significant positive correlation was found between the percentage of these cells and that of any T cell subsets tested.
Complement Activation↗
The pattern of activation antigen expression on T-lymphocyte subpopulation in infectious mononucleosis.
The peripheral blood mononuclear cells of patients with infectious mononucleosis (IM) have been characterized by the determination of activation antigens using a panel of 11 monoclonal antibodies (MoAbs) belonging to 9 clusters. The activation of CD8+ peripheral blood mononuclear cells of IM patients was found to be determined by HLA-DR and CD45RO MoAbs. The antibodies of the CD30, CD40 and CD70 termed antigens also showed an increased expression as compared to the controls. In contrast, the CD25, CD69, CD71, and CD45 antigens were expressed at a low rate on the surface of the CD8+ cells. We found, on the other hand, a very low percentage of B lymphocytes in the peripheral blood, which reflects on the virus caused antigen modulation and on the effectivity of activated CD8 cells with the characteristic expression of the above outlined markers in IM. In six asymptomatic patients, the percentage of CD8+HLA-DR+, as well as of CD8+CD45RO+ cells proved to be lower than that in the active phase of the disease. The number of B cells showed normal value in the clinically asymptomatic cases.
Adolescent↗
Age dependency of the progression of HIV disease in haemophiliacs; predictive value of T cell subset and neopterin measurements.
Sixteen HIV-seropositive haemophiliacs were followed up for 42 months and 9 other patients for 24 months. All patients were infected in 1983 or 1984. T cell subsets and serum neopterin levels were measured twice a year. The patients were divided into three groups according to their age in 1989: group A (children) less than 14 years old (n = 6); group B (adolescents) 14-20 years old (n = 8); group C (adults) greater than 20 years old (n = 11). At the last measurement performed in November, 1989, patients of group A had significantly higher absolute number and percentage of CD4+ lymphocytes and significantly lower serum neopterin levels than patients of group B and C. In addition, the percentage of the activated, CD3+ DR+ lymphocytes was also significantly higher in the adult-adolescent group than in the children group. Until the end of December, 1989, AIDS developed in 0, 1 and 2 patients and ARC was diagnosed in 0, 5, and 2 patients of groups A, B, and C, respectively. The progression of the HIV disease towards AIDS in these patients was predicted by the T cell subset and neopterin measurements performed in 1987. Only those 3 patients who progressed to AIDS had CD4+ cells less than 350/microliters and a neopterin value of more than 20 nmol/l. These findings confirm previous observations indicating that in patients with haemophilia the progression of HIV disease is influenced by age: a relatively slow progression can be expected in prepuberty children.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Correlation of HIV core antigen, antibody and immune complex levels in sera of HIV-infected individuals.
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Antigen-Antibody Complex↗
Detection of HIV in the peripheral mononuclear cells of asymptomatic haemophiliacs in Hungary.
The presence of virus in peripheral blood mononuclear cells of asymptomatic antibody positive haemophiliacs was detected by assaying for reverse transcriptase and confirmed by electron microscopy and immunofluorescence. HIV has been detected in 5 out of 7 individuals. In order to investigate strain variation, supernatant fluids of cultures were added to H9 and MT-4 cells. Virus was recovered in MT-4 cells in 3 cases, whereas the H9 cells only supported the replication of 2 strains. Viruses isolated from asymptomatic haemophiliacs have a narrower range of infectivity than HTLV-IIIB.
Acquired Immunodeficiency Syndrome↗
Neutralizing antibodies and serum interferon levels in the different stages of HIV infection.
The sera of patients infected with HIV were investigated for neutralizing antibodies (NA) and interferons. All samples from asymptomatic HIV carriers contained NA in high titres. In the sera of patients with AIDS related complex and AIDS the antibodies were found rarely and in lower titres. An early peak of acid-labile interferon (IFN)-alpha was observed in asymptomatic HIV-infected persons, and a late peak was found in AIDS patients. The data suggest that HIV NA may have beneficial effect in the asymptomatic phase. The presence of acid-labile IFN-alpha may indicate stimulation of IFN system by HIV-infected cells.
AIDS-Related Complex↗
E. coli antibodies do not cause false-positivity in recombinant anti-HIV assays.
129 sera with known antibody titres against E. coli 026 and E. coli 055 strains were tested with the Abbot second generation anti-HTLV III recombinant screening assay. No difference in the O.D. values was found between sera with high, normal and low anti-E. coli titres. In addition, no false-positive reactions were observed with the anti-HIV negative sera containing E. coli antibodies in high titres in a Western blot assay in which recombinant env antigen was applied. These results suggest that E. coli assays in which E. coli-produced recombinant antigens are used.
Antibodies, Bacterial↗
[False positive results of HIV virus tests in patients undergoing chronic hemodialysis].
The sera of 173 haemodialysis patients treated in two dialysis centers in Hungary were tested for the presence of HIV (HTLV III/LAV) antibodies. Four different commercial enzyme immunoassay (EIA) kits and two types (CEM/LAV, and H9/HTLV III) of indirect immunofluorescence assay (IFA) were used. The Western blot technique was applied as confirmatory test in the study. No confirmed positive results were found in any of the cases. However, in 15 patients (8.7%) false positive (not confirmable by the Western blot assay) results were obtained in at least one but mostly in all of the three type 1 EIA kits (ORGANON, ELECTRONUCLEONICS, SORIN) applied. In 4 patients, the IFA assay also gave false positive results which could be repeated in sequential samples taken from the same patients. Increased reactivity in the control plate (coated with a concentrate of cellular material shed by uninfected H9 cell line) of the SORIN kit was found only in a few false positive samples and no fluorescence with the uninfected H9 or CEM cells was observed in any of the sera showing a false positive IFA. These results indicate that the false positive anti-HIV results frequently observable in haemodialysis patients are not simply the consequence of the presence of antibodies reacting with the uninfected H9 and/or CEM cells but they are most probably due to antibodies against antigens expressed on these cells only after infection with the human immunodeficiency virus.
False Positive Reactions↗
Different types of false positive anti-HIV reactions in patients on haemodialysis.
Serum samples of 589 haemodialysis patients were screened for HIV antibody by ELISA methods. Of these, 36 samples were found to be repeatedly reactive. None of the 36, however, could be confirmed by competitive enzyme immunoassays and Western blot; therefore, they were considered to be false positive. The sera could be divided in two groups. The sera of Group 1 were designated as the usual type of false positivity, caused most probably by anti-lymphocyte antibodies. In 19 sera, however, a special type of false positivity was found. These sera reacted strongly with the plates coated with the supernatants of HIV-infected cells but not with those of uninfected H9 cells. Three and two sera showed, respectively, positive immunofluorescence reaction with the HIV-infected, but not with the uninfected, H9 and CEM cells. Reactivity to HIV-infected H9 cells could be adsorbed from a part of these samples with lesser amounts of HIV-infected than uninfected H9 cells. This special type of false positivity was observed frequently (7/65) in patients who rejected a kidney graft. These findings suggest that this type of anti-HIV false positivity is due to antibodies reacting with cellular antigens present in HIV-infected but not in uninfected lymphocytes. Their appearance seems to be associated with the immunological activation occurring at graft rejection.
Blotting, Western↗
Effect of pepsin treatment on the HIV envelope and core antigens.
In order to clarify whether HIV-1 core and env antigens are destroyed during pepsin treatment, used previously for detecting HIV-1 core and env antibodies hidden in circulating immune complexes, purified recombinant env and core antigen preparations were treated with pepsin. Core antigen was found to be extremely sensitive to this enzyme. By contrast, the antigenicity of the purified env antigen was not destroyed and was even increased after pepsin treatment, performed under identical conditions. These findings suggest that after pepsin digestion the core-anti-core immune complexes do not reconstitute because of the loss of antigenicity of the core antigen. By contrast, the lack of binding after neutralization to the env antigen of the F(ab')2 fragment of the anti-env antibody, cleaved by pepsin from the immune complexes, is probably due to other factors.
Antigen-Antibody Complex↗
Complement-dependent cytotoxicity of antibodies reactive with HIV-induced cell surface antigens in HIV-carrying haemophiliacs.
Sera obtained from HIV-infected as well as uninfected haemophiliacs and from healthy subjects were investigated for the presence of lymphocytotoxic antibodies. Using the 51Cr-release test, HIV-infected haemophiliacs were found to produce serum antibodies exerting complement-dependent cytotoxic effect on HIV-infected T4 cells. The antibodies were reactive mainly when HIV-infected target cells were stimulated with concanavalin-A. Results of complement-dependent antibody cytotoxicity and indirect membrane immunofluorescence tests suggest that envelope antigen(s) of HIV may be the target(s) for cytotoxic antibodies.
Acquired Immunodeficiency Syndrome↗
Pitfalls in HIV serology: reagent-dependent changes in sensitivity and specificity of ELISA kits.
Using confirmed positive and false-positive serum samples stored in deep frozen state we studied the reproducibility of the results obtained by different anti-HIV enzyme immunoassay (EIA) kits. Experiences obtained with 3 kits are presented. Two types of observations were made: (a) significant inter-lot, intra-lot and even inter-box sensitivity difference was found with some kits and (b) reactivity of the plates for true-positive and false-positive sera independently changed among different lots of the same kit: while reactivity for true positive sera was constant, a significant decrease or increase in reactivity for false-positive sera was found. These observations point to poor reproducibility of some commercial anti-HIV EIA kits that can cause serious difficulties in screening laboratories.
Enzyme-Linked Immunosorbent Assay↗
[T lymphocyte subpopulation in respiratory allergy].
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Asthma↗