Humoral immune responses to gag and env proteins from human immunodeficiency virus type 1 in hemophiliac patients (original) (raw)
Related papers
Clinical and Diagnostic Laboratory Immunology
Retrospective analysis of serum samples from a group of hemophiliac patients who became infected with human immunodeficiency virus type 1 (HIV-1) between 1984 and 1985 has shown that, at variance with other HIV-1-infected patients, at the onset, or at least at a very early phase of HIV-1 infection, they constantly have elevated levels of antibodies against HIV-1-transactivating Tat protein and an absent or barely detectable p24 antigenemia. Anti-Tat antibodies in initial serum samples from hemophiliac patients were probably the consequence of the passive administration of immunoglobulins present in low-or intermediate-purity clotting factor concentrates prepared from HIV-1-infected blood. Furthermore, the analysis of serial serum samples obtained during the course of the disease, in which passively acquired anti-Tat antibodies were substituted by actively produced antibodies, demonstrated an inverse relationship between anti-Tat antibody and p24 antigenemia levels throughout the observation period. These data seem to suggest that anti-Tat antibody may have some influence on the course of HIV-1 infection.
Clinical and Experimental Immunology, 2008
The use of serological tests for the diagnosis of HIV infection has revealed that some non-infected persons have antibodies that react with HIV-1 gag proteins. Here, the sera of three non-infeeted subjects reacting with p 17 and 11 non-infected subjects reacting with p24 were investigated, using an enzyme immunoassay (EIA) with six reeombinant gag antigens and Western blot analysis of proteolytic peptides of two of these ^og antigens. The results indicate that whereas all pl7-reactive sera eould react with an unique epitope, individual p24-reactive sera reeognize dilTerent epitopes. Investigations by EIA also demonstrated the role of sequences located far from the epitopes in making these epitopes accessible to the antibodies or in providing them with an antigenic conformation. In addition to the 14 subjects mentioned above, another subject was shown to have antibodies reacting with the p9 (NC) gag protein. Several proteins are known as having homology with HIV-1 gag proteins. Their possible role in eliciting cross-reactive antibodies is discussed.
Antibody Response in Primary Human Immunodeficiency Virus Infection
The Lancet, 1987
The antibody response in 20 homosexual men with symptomatic primary HIV infection was studied with ten different antibody assays (enzyme-linked immunosorbent assays, indirect immunofluorescence assays, radioimmunoprecipitation [RIPA], and western blot). HIV antibodies were detectable by all the assays within 2 months after onset of illness. RIPA and western blot were more sensitive than the other assays—all serum samples obtained at 2 weeks and after were reactive. In all cases, the first serum sample reactive by RIPA precipitated gp160 whereas, by western blot, antibodies to p24 were first recognised. This study shows the necessity of including gp160 and p24 in any assay to detect early antibody response in primary HIV infection. 5 patients were studied by virus isolation. During the 2 first weeks after onset of symptoms, HIV was demonstrated in cell-free plasma in all cases and, in 4 cases, also in peripheral blood mononuclear cells. Samples obtained later contained demonstrable infectious virus in only 1 of 4 cases. Thus a phase of viraemia precedes the antibody response in symptomatic primary HIV infection.
Serum samples with indeterminate Western blot (WB) tests from 61 individuals whose sera were positive by enzyme-linked immunosorbent assay (ELISA) were studied in order to characterize their putative reactions with the human immunodeficiency virus (HIV) proteins and to resolve the HIV infection status of these individuals. The reaction observed by WB could not be confirmed either by radioimmunoprecipitation assay and subsequent electrophoresis (RIPA) or by use of LiaTek (Organon Teknika, Turnbout, The Netherlands) in 28% of the samples. Of the 86 samples that were indeterminate by WB, 66 reacted with p24 by WB; this reaction was confirmed by RIPA in only 21 (32%) and by LiaTek in 49 (74%) of the 66 samples. On the other hand, none of the indeterminate samples that reacted with HIV envelope proteins by WB did so by LiaTek, while 50%o precipitated at least some of these proteins in the RIPA. The sensitivities of the three methods for detecting the antibody reaction with the different HIV proteins, which were studied with serial dilutions of positive serum samples, were similar. Thus, a lower sensitivity of RIPA or LiaTek does not seem to be the cause for the lack of reaction of the WB-indeterminate samples by these two methods. Sequential samples from individuals whose serum samples reacted by the three methods gave reproducible results, but all showed low antibody titers. Peripheral blood mononuclear cells obtained from three of the four individuals with sequential samples that reacted with HIV env proteins by WB and RIPA were negative for HIV provirus DNA after amplification by the polymerase chain reaction.
Journal of Clinical Microbiology, 2002
The humoral immune response of the human host against the human immunodeficiency virus (HIV) type 1 (HIV-1) envelope glycoproteins comprises virus-neutralizing antibodies (NAs), antibody-dependent cellular cytotoxicity-mediating (ADCC) antibodies, and infection-enhancing antibodies (IEAs). Because of their potential significance for the outcome of infection with this virus, we have studied the relative prevalence of NAs, ADCC antibodies, and IEAs in the sera of patients infected with HIV. Our results demonstrate that while >60% of serum samples are positive for NAs or ADCC antibodies, 72% of these serum samples mediate the enhancement of infection in the presence of complement. In patients with low CD4 counts, NA and ADCC antibody levels tend to decrease, while IEA levels increase. A significant positive correlation was found only between the presence of ADCC antibodies and the presence of antibodies that neutralized HIV-1 in the presence of complement. These results show that the anti-HIV-1 humoral immune response consists of a mixture of antibodies that may inhibit or enhance HIV infection and whose ratios may vary in different stages of the infection.
Clinical Immunology and Immunopathology, 1996
After acute infection and before the onset of clinical The objective of the present study was to evaluate symptoms, infected individuals remain asymptomatic the prognostic utility in determining the risk of AIDS for a variable period of time. During this stage the progression in HIV-1-infected asymptomatic hemopredictive criteria to select the subjects at highest risk philiacs by in vitro immunoglobulin (Ig) synthesis. for rapid disease progression have yet not been identi-With this aim, a cohort of 28 HIV-1-seropositive hemofied. It is generally accepted that HIV-1 affects the imphiliacs were studied. All showed the number of CD4 mune system in the asymptomatic period before quanlymphocytes higher than 400 positive cells/mm 3. In all titative depletion of CD4 T cells occurs (1-4). As a matcases the spontaneous and pokeweed mitogen-induced ter of fact, B cell abnormalities have been observed in vitro production of Ig by peripheral blood lymphoearly after HIV seroconversion. Patients with a still cytes was evaluated at the beginning of the study and normal CD4 lymphocyte count have been reported to the ratio stimulated/spontaneous (Stim/Spon) syntheproduce a spontaneously high rate of immunoglobulin; sis was calculated. At the same time, the absolute CD8 / this finding is associated with in vitro reduced response cell count, IgA serum immunoglobulin, p24 HIV-1 antito pokeweed mitogen (PWM) (5-8). These abnormaligenemia, and b 2 microglobulin were calculated. These ties were considered as a corollary phenomenon of HIVdata were monitored during the 4-year follow-up of 1 infection without a well-defined clinical impact. This patients and compared with the stimulated/spontanestudy was designed to assess the prognostic utilities of ous Ig synthesis ratio to evaluate the predictive significance on the progression of HIV infection. Ac-in vitro immunoglobulin (Ig) production over a 4-year cording to the stimulated/spontaneous Ig synthesis ra-follow-up in determining the rate of CD4 T lymphocyte tio, hemophilic patients were separated into two decrease and disease progression in asymptomatic categories. Group I included 12 subjects with a Stim/ HIV-1-seropositive hemophiliacs with a CD4 count Spon ratio higher than 2 (the lowest value of normal higher than 400 positive cells/mm 3. We compared in controls) and group II included 16 cases with a ratio vitro Ig synthesis with the other established markers lower than 2. As control, in 36 HIV-1-negative hemoof progression of HIV-1 infection, namely, CD8 lymphophiliac individuals the stimulated/spontaneous Ig racyte count (9-12), IgA serum antibody titer (13, 14), tio ranged between 2 and 42; mean { SEM, 12.9 { 1.8. p24 HIV-1 antigenemia (15, 16), and levels of b 2 mi-At the end of the 4-year follow-up, group I patients croglobulinemia (17, 18). showed a CD4 count and clinical staging consistent with those of the first evaluation; in contrast group II MATERIALS AND METHODS demonstrated a significant decrease in CD4 lymphocytes and deterioration of clinical conditions. Our re-Patients. From 1989 to 1990 28 HIV-1-seropositive sults show that a low Stim/Spon Ig ratio when the CD4 hemophiliac patients entered the study. All these palymphocyte count was still normal appears to predict tients were asymptomatic, with the number of CD4 / T the depletion of this lymphoid subset and progression to AIDS before T CD8, IgA immunoglobulin, p24 HIV-lymphocytes higher than 400 positive cells/mm 3 , at the 1 antigenemia, and b 2 microglobulin abnormalities. In time of the first evaluation. All of them suffered from this setting, the stimulated/spontaneous Ig ratio may severe type A hemophilia (less than 1% factor VIII) represent a useful tool for clinical decisions in HIV-1and had previously received factor VIII or factor IX infected hemophiliacs.
Global Journal of Health Science, 2010
This work was designed to characterize the HIV viral antibodies in HIV infected and non-HIV infected HBsAg seropositive patients. Fifty non HIV infected (male = 25; female = 25)and 50 HIV infected HBsAg seropositive patients (male -n = 25; female -n = 25) aged 6 -64 years recruited from the medical outpatient department of Baptist Medical Centre, Saki -Oyo State -Nigeria were investigated as test subjects. Fifty apparently healthy HIV and HBsAg seronegative individuals (male = 25; female = 25) aged 4 -72years were recruited as control subjects. All subjects were counseled and were subjected to HBsAg and HIV immunoassays by Enzyme Linked Immunosorbent Assay and Western blot assay. All subjects were monitored for twelve months. The subjects were investigated on recruitment and 12months after recruitment. The result obtained indicated higher frequency of occurrence of each of the HIV antibodies to each of the viral proteins in HIV infected HBsAg seropositive patients than in non HIV infected HBsAg seropositive patients (94% vs 0% (gp 160,), 84% vs 0% (gp 120), 94% vs 4% (p66), 94% vs 4% (p51), 84% vs 0% (gp 41), 94% vs 0% (p31), 100% vs 24% (p24) and 84% vs 6% (p17) during the first bleeding. The result obtained after 12 months showed a slight difference with the expression of antibody to gp41 by 4% of the non HIV infected HBsAg seropositive patients in addition to antibody to p24 or p17 which confirms HIV infection. Some of the non HIV infected HBsAg seropositive patients expressed antibodies to the following proteins p66, p51, p24, p17 during the initial investigation and after 12 months. The frequency of occurrence of antibody to p24 obtained in all HIV -HBsAg and some of the non HIV infected HBsAg seropositive patients was higher compared antibodies to other HIV proteins. This recent work has therefore been used to suggest the possibilities of antibodies to HIV viral proteins (p66, p51, p24, p17) in HBsAg seropositive sera. It also confirms an encouraging degree of specificity of antibodies to HIV envelope glycoproteins (gp160, gp120, gp41) in the diagnosis of HIV infection.