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Biomedical subjects

B Böttiger

Publications and source records attributed to B Böttiger.

At least 37 records · Page 2Linked to original sources

Immunological changes in primary HIV-1 infection.

Homosexual men with symptomatic primary HIV-1 infection displayed a pronounced lymphopaenia with significantly depressed numbers of CD3+, CD4+ and CD8+ cells and B cells during the first week of illness. Subsequently, the CD8+ cell counts rose in parallel with numbers of CD3+ cells, atypical lymphocytes and activated (CD38+ and HLA-Dr+) cells to attain maximal levels about a month following onset of illness. In contrast CD4+ and B cell numbers remained low for an extended period of time. Early signs of a host response included a transient appearance of interferon-alpha in the blood and raised levels of neopterin and beta 2-microglobulin (beta 2-M). Neither CD4+/CD8+ cell ratio nor beta 2-M resumed completely normal values during a follow-up period of 2 years. These findings shed some light on pathogenetic events during early HIV-1 infection and suggest that the infection, following the acute symptomatic stage, usually enters a stage of chronic active rather than latent infection.

Adult↗

Envelope cross-reactivity between human immunodeficiency virus types 1 and 2 detected by different serological methods: correlation between cross-neutralization and reactivity against the main neutralizing site.

A total of 70 human immunodeficiency virus type 1 (HIV-1) and 42 HIV-2 antibody-positive serum samples, collected from groups of individuals in which only one type of HIV prevails, were tested for cross-reactivity against HIV-2 and HIV-1 proteins by Western blot (WB) (immunoblot), radioimmunoprecipitation assay (RIPA), neutralization analysis, and enzyme-linked immunosorbent assay with as antigen synthetic peptides representing selected parts of the envelope (env) glycoproteins. Cross-reactions against the env glycoproteins were observed by WB in 10% (7 of 70) and by RIPA in 40% (28 of 70) of the HIV-1 antibody-positive serum samples and by WB in 29% (12 of 42) and by RIPA in 48% (20 of 42) of the HIV-2 antibody-positive serum samples. Testing by enzyme-linked immunosorbent assay against a 36-amino-acid peptide (Cys-301-Cys-336) of the external glycoprotein of strain HTLV-IIIB of HIV-1 (HIV-1HTLV-IIIB) (known to represent a dominating, linear neutralizing site) showed type-specific reactions in 67% (38 of 57) of HIV-1 antibody-positive serum samples. Type-specific reactions against a homologous 35-amino-acid peptide of strain SBL-6669 of HIV-2 (HIV-2SBL-6669) were found in 75% (30 of 40) of HIV-2 antibody-positive serum samples, and these reactions were correlated to neutralization against HIV-2SBL-6669. Cross-reactions against these peptides were seen in 23% (13 of 57) and 33% (13 of 40) of the HIV-1 and HIV-2 antibody-positive serum samples, respectively. These cross-reactions were correlated to cross-neutralization against HIV-1HTLV-IIIB and HIV-2SBL-6669. Cross-neutralization against one heterotypic virus strain was demonstrated in 16% (9 of 57) of HIV-1 antibody-positive serum samples and in 22% (5 of 22) of HIV-2 antibody-positive serum samples, but no correlation was found between cross-neutralization and env cross-reactivity in WB or RIPA.

Blotting, Western↗

Cross-neutralizing antibodies against HIV-1 (HTLV-IIIB and HTLV-IIIRF) and HIV-2 (SBL-6669 and a new isolate SBL-K135).

A total of 57 HIV-1 antibody-positive sera and 43 HIV-2 antibody-positive sera were all tested for neutralizing capacity against two HIV-1 isolates (HTLV-IIIB and HTLV-IIIRF) and two HIV-2 isolates (SBL-6669 and SBL-K135). SBL-K135 is a new HIV-2 isolate obtained from a patient with clinical AIDS from Guinea-Bissau. Among the HIV-1--positive sera, 84% neutralized any of the HIV-1 isolates, 67% neutralized both HIV-1 isolates, and 35% neutralized any of the HIV-2 isolates. Among the HIV-2--positive sera, 91% neutralized any of the HIV-2 isolates, 67% neutralized both HIV-2 isolates, and 37% neutralized any of the HIV-1 isolates. Thus, neutralizing antibodies in HIV-1-- and HIV-2--positive sera can be cross-reacting, type-specific, or strain-specific. The cross-neutralizing titers were lower than the neutralizing titers against the type-specific viral isolates. The presence of cross-neutralizing antibodies was related to the presence of neutralizing antibodies against both type-specific isolates.

Acquired Immunodeficiency Syndrome↗

Natural history of HIV infection in Swedish haemophiliacs.

The longitudinal follow-up is described of 36 anti-HIV positive haemophiliacs who had seroconverted in the period 1980-82, and of 41 seronegative controls. Laboratory variables were followed up for a mean duration of 2.5 years (1985-87). Of the 36 seropositive patients, AIDS developed in 3, and generalised persistent lymphadenopathy in 9. The HIV-seropositive patient group had lower CD4:CD8 ratios and CD4 counts but higher CD8 counts than the seronegative group. However, there was no deterioration in the values for the lymphocyte subsets during follow-up. Titration on paired sera showed an increase in anti-HIV titre with time. Testing for the presence of HIV antigen was positive in 5 patients, including 2 who later developed AIDS. We conclude that anti-HIV positive haemophiliacs, though actively immunised, often show no symptoms even as long as 7 yr after seroconversion and that, in certain patients, the immune system may even show signs of improvement.

Acquired Immunodeficiency Syndrome↗

Follicular involution in HIV lymphadenopathy. A morphometric study.

Lymph node biopsies from 75 HIV infected patients (71 homo- and bisexual men, 3 hemophiliacs and 1 woman) were studied using immunohistochemical methods with monoclonal antibodies (Mabs) against B lymphocytes, subsets of T lymphocytes, follicular dendritic cells (FDC) and HIV gag proteins p24 and p18. Histopathological changes were classified as follicular hyperplasia (FH), fragmentation (FF), atrophy (FA) and depletion (FD). Immunohistochemical stainings were quantified with the help of an Image Quantifier (IQ) and the reactivity for respective Mab-defined antigen was related quantitatively to other antigens and histopathological changes. Such measurements showed an increase in FDC in biopsies with FH and FF histology and a decrease in FA and FD cases in comparison with cases with non-HIV related lymphadenopathy. In addition it was found that the decrease in FDC was correlated with an increase in CD8+ within the follicles. Double immunostainings for p24 and various cellular markers showed that p24 was predominantly associated with follicular dendritic cells. Essentially the same findings were observed in the lymph nodes irrespective of risk group. Possible mechanisms involved in follicular involution in HIV-related lymphadenopathy are discussed.

AIDS-Related Complex↗

Predictive markers of AIDS: a follow-up of lymphocyte subsets and HIV serology in a cohort of patients with lymphadenopathy.

From 1982 to 1985, 89 HIV-1 seropositive men with persistent generalized lymphadenopathy (PGL) were enrolled into a prospective longitudinal study. In February 1988, after a mean observation time of 45 months, 23 patients had progressed to AIDS with opportunistic infection (AIDS/OI), 4 had developed Kaposi's sarcoma, 47 had developed HIV-related symptoms, 14 still had PGL as only symptom, and 1 was lost to follow-up. Patients with CD4 lymphocytes less than or equal to 0.40 x 10(9)/l as well as patients with HIV antigenaemia and those lacking antibodies to p24 all had a significantly higher risk of developing AIDS/OI within 30 months of observation than other patients. HIV antigen was present in 70% and antibodies to p24 were lacking in 61% of the patients at the time of AIDS/OI diagnosis. All but one (96%) of the AIDS/OI patients had CD4 numbers less than or equal to 0.20 x 10(9)/l at the same time. The estimated median time to AIDS/OI in patients with HIV antigenaemia was 21 months and in patients lacking p24 antibodies 27 months. In patients with CD4 numbers less than or equal to 0.20 and 0.40 x 10(9) cells/l the estimated median time to AIDS/OI was 14 months and longer than 30 months, respectively.

Acquired Immunodeficiency Syndrome↗

Experimental infection of cynomolgus monkeys (Macaca fascicularis) with HIV-2.

Ten healthy adult cynomolgus monkeys (Macaca fascicularis) were inoculated with two different isolates of human immunodeficiency virus type 2 (HIV-2), SBL-6669 and SBL-K135, to establish an animal model for HIV infection. HIV-2SBL-6669 had been propagated for a long time in continuous human cell lines whereas HIV-2SBL-K135 had been grown only in fresh human and monkey lymphocyte cultures or previously for a short time in a continuous cell line. Virus was isolated from three or four animals inoculated with HIV-2SBL-K135 but in none of six monkeys inoculated with HIV-2SBL-6669. All animals seroconverted although the antibody response was higher in SBL-K135 virus-infected monkeys. Varying degrees of lymphadenopathy were observed but there were no significant changes in the numbers of CD4+ and CD8+ T cells. The infection was transferred to two monkeys inoculated with blood from a previously SBL-K135 virus-infected monkey. Four animals inoculated with HIV-2SBL-K135, which had never been propagated in continuous human cell lines, showed strong antibody responses against both gag- and env- encoded proteins of HIV-2. None of the SBL-6669 infected monkeys showed antibodies to core proteins. HIV-2 infection of cynomolgus monkeys represents a useful experimental model for HIV vaccine trials and antiviral testing.

Acquired Immunodeficiency Syndrome↗

HIV-serology and lymphocyte subsets in relation to therapy and clinical development in haemophiliacs.

389 Swedish patients with haemophilia A, B or von Willebrand's disease were examined for HIV-1 antibodies. T-cell subsets were measured in 260 of them. HIV-1 antibodies were found in 98 of these patients. Of the 199 patients with severe or moderate haemophilia A, 44% were seropositive. They had seroconverted between 1979 and 1983. HIV-1-seropositive patients had significantly decreased numbers of CD4 cells and increased numbers of CD8 cells. The seronegative haemophilia A patients had significantly increased numbers of CD8 cells. The T-cell subsets were followed for a median of 40 months in 73 seropositive patients. All groups of patients, at different clinical stages, showed decreasing numbers of CD4 cells. The most pronounced decrease was seen in the patients who developed AIDS, followed by the group which developed HIV-related signs or symptoms. HIV antigen in serum and antibody pattern in Western blot and ELISA were followed in 89 patients. HIV-1 antigen was present and p24 antibodies were lacking in 11% and 13% of asymptomatic subjects, in 13% and 20% of patients with persistent generalized lymphadenopathy, in 33% and 38% of patients with other HIV-related signs or symptoms and in 5/6 of the AIDS patients, respectively. In conclusion, the decrease of CD4 cells and the presence of HIV antigen and/or absence of p24 antibodies were found to be prognostic markers for HIV disease.

Acquired Immunodeficiency Syndrome↗

Prevalence of HIV-1 and HIV-2/HTLV-IV infections in Luanda and Cabinda, Angola.

A seroepidemiological study of human immune deficiency virus type 1 (HIV-1) and HIV-2/human T-lymphotropic virus type IV (HIV-2/HTLV-IV) infections was performed in Angola in October 1986. Until then five cases of acquired immune deficiency syndrome (AIDS) had been registered in Angola. During this study, another three cases with clinical AIDS were found and confirmed by HIV-1 serology. A total of 1,215 sera from groups of healthy persons and patients were tested for HIV-1 and HIV-2/HTLV-IV antibodies by enzyme-linked immunosorbent assays (ELISA). Sera positive by ELISA were also tested by Western blot (WB) analysis. In Luanda, the capital, HIV-1 antibodies were demonstrated in 0.4% (2/452) of male blood donors, in 0.3% (1/357) of pregnant women, in 1% (1/100) of tuberculosis patients, in 4% (4/94) of patients at medical wards, and in none of 22 women hospitalized with pelvic infections. In the Cabinda province, 11% (4/38) of postnatal women at a maternity ward were found to be HIV-1 seropositive, but only 2% (1/55) of other hospitalized patients and none of 32 male blood donors or 59 healthy persons in a village on the border to Zaire. Specific antibodies to HIV-2/HTLV-IV were not found in any of the sera. However, 16 out of 17 HIV-1 positive sera cross-reacted with HIV-2/HTLV-IV core proteins by WB. In October 1987, 280 of the blood donors from Luanda were retested for HIV-1 antibodies and one of them was found to have seroconverted during the previous year.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Neutralizing antibodies in relation to antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus type I.

The presence of neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) was investigated in sera from 73 HIV-1 seropositive subjects at different clinical stages. Virus neutralization was measured as survival of MT-4 cells in a 6-7 day microassay. Sixty-three sera were also tested for antibodies inducing virus-specific antibody-dependent cellular cytotoxicity (ADCC). Neutralizing antibodies were found in 59% of sera tested, the positivity rate being 50% (9/17) in asymptomatic subjects, 67% (12/18) in patients with persistent generalized lymphadenopathy (PGL) and 54% (14/26) in AIDS patients (not significant differences). ADCC antibodies were present in 43% of the sera. Neutralizing antibodies and ADCC-inducing antibodies were found simultaneously in 35% (22/63) of the sera. Neutralizing antibodies alone were found in 22% (14/63) and ADCC antibodies alone in 6% (4/63) of the sera tested. Thirty-seven per cent (23/63) of the sera were negative for both types of antibodies, 62% of the sera with neutralizing antibodies also had ADCC inducing antibodies and 85% of the sera with ADCC antibodies had neutralizing antibodies. The titres of ADCC antibodies were higher than those of neutralizing antibodies. Thus, the presence of ADCC antibodies was related to the presence of neutralizing antibodies, but no correlation was found between the titres of these antibodies in sera positive for both activities.

AIDS-Related Complex↗

Antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus. Presence at different clinical stages.

The presence of antibodies mediating antibody-dependent cellular cytotoxicity (ADCC) against human immunodeficiency virus (HIV)-infected target cells was investigated with 170 sera from patients with varying severity of HIV infection. Approximately 40% of sera from individuals representing all stages of infection were ADCC-positive when tested against HTLV-IIIB infected 0937 clone 2 target cells. The positive sera had higher HIV antibody titers as measured by enzyme-linked immunosorbent assay compared with ADCC-negative sera. ADCC titers were lower in patients with acquired immune deficiency syndrome than in asymptomatic carriers. This decline in ADCC titer was not correlated with a general decrease of HIV antibodies. No correlation between the CD4:CD8 lymphocyte ratio and ADCC activity was found. The possible beneficial effect of ADCC-inducing antibodies early in infection is discussed in relation to the effect of ADCC-inducing antibodies in other retrovirus systems and to the nature of lentivirus infections.

AIDS-Related Complex↗

Radioimmunoprecipitation and Western blotting with sera of human immunodeficiency virus infected patients: a comparative study.

The sensitivity and specificity of radioimmunoprecipitation assay (RIPA) and Western blot (WB) test were compared by use of a collection of 183 sera, representing different categories of individuals, noninfected or infected with the human immunodeficiency virus (HIV). The sera were subdivided on the basis of their reactivity in at least two anti-HIV enzyme-linked immunosorbent assays (ELISA); 53 sera were negative and 61 sera were positive in both tests, whereas 69 sera showed ambiguous reactions. The reaction patterns in RIPA could be divided into 6 different groups. The same grouping could to some extent be applied to the results of WB test. RIPA provided the most efficient means for identification of the large viral envelope glycoproteins, gp120/160, whereas gp41 was detected more effectively by WB. Internal virus components reacted to a varying extent with specific antibodies in the two tests. The reaction with pol products was more pronounced with the WB tests in which extracellular material was used as antigen. In a few WB tests, however, the reaction with internal components did not reflect a prior HIV infection. No such ambiguity was observed with RIPA, reflecting the advantage of a test that uses a minimally denaturated antigen and provides appropriate conditions for identification of the large viral glycoproteins. The practical choice of confirmatory tests to be used in diagnostic laboratories requires evaluation of both the sensitivity and specificity of the tests but also their economy and convenience.

Acquired Immunodeficiency Syndrome↗

A new human retrovirus isolate of West African origin (SBL-6669) and its relationship to HTLV-IV, LAV-II, and HTLV-IIIB.

A new human retrovirus of West African origin (SBL-6669) has been isolated from a patient with immunological and clinical signs of immunodeficiency. Using radioimmunoprecipitation assays (RIPA) and Western blot (WB) tests with human sera, the new virus isolate has been compared with HTLV-IV, LAV-II, and the HTLV-IIIB prototype strain of the human immunodeficiency virus (HIV). The West African isolates appeared to be members of the same virus group since their glycoproteins were antigenically indistinguishable. West African sera showed no detectable cross reaction with HTLV-IIIB glycoproteins. The external glycoprotein in the different virus strains only showed minor variations in size. The size of the transmembranous protein was not unambiguously defined. In the West African virus isolates a 30-35 kD protein was seen similar to the protein previously described possibly to represent this component. However, in SBL-6669 a distinct 41 kD protein was also identified. There were interstrain variations in the size of several viral proteins among the West African virus isolates. Only minor differences were seen between SBL-6669 and LAV-II. The variations were most pronounced in two core proteins corresponding to the 19 kD and 24 kD proteins of HTLV-IIIB. In addition, West African human retroviruses appear to differ in pathogenicity. LAV-II and SBL-6669 are associated with immunodeficiency, whereas HTLV-IV was isolated from healthy individuals. Since further spread of these viruses to other parts of the world is imminent, it is necessary to consider their antigenic and immunogenic properties in serodiagnosis of HIV infections and in planning for immunoprophylactic interventions.

Antigens, Viral↗

HIV seroconversion in Swedish haemophiliacs: relation to type and dosage of factor concentrate.

Human immunodeficiency virus (HIV) seroconversion among 40 Swedish haemophilia A patients has been investigated by retrospective sera testing. 22/40 patients had developed HIV antibodies before 1983, i.e., when heat-treatment of American factor concentrates was introduced. All patients had received American and Swedish factor concentrates, thus no case of seroconversion was seen among patients treated exclusively with non-heat-treated Swedish concentrates. Of 79 patients with severe or moderate haemophilia, all of whom had received both American and Swedish concentrates, the 36 seropositives were compared with the 43 seronegatives. The total number of units received did not differ between the two groups, though the seropositive group had received significantly more American concentrate. Two batches of concentrate were proved to have been infected. 29 seropositive and 13 seronegative patients had been treated with at least one of these batches. As expected, and unlike most of the seronegative patients, patients in the seropositive group generally had abnormal lymphocyte subsets.

Acquired Immunodeficiency Syndrome↗

Histopathology and immunohistology of HTLV-III/LAV related lymphadenopathy and AIDS.

Fifty-nine lymph node biopsies from homosexual men with serum antibodies to HTLV-III/LAV were the subject of a detailed histopathological and immunohistochemical study. The histological findings were correlated to the patients clinical status, and the T4/T8 ratios in blood and lymph nodes. Four histological patterns predominated and were defined as follicular hyperplasia (FH), follicular fragmentation (FF), follicular atrophy (FA), and follicular depletion (FD). Immunocytochemical studies indicated that destruction of follicular dendritic cells is related to the initiation of follicular involution from FH to FF, but the possible role of follicular infiltrating T-cells cannot be excluded. Marked individual variations in lymph node angiogenesis increasing during involution were observed, which suggests that the degree of angiogenic host response may predispose for evolution of Kaposi's sarcoma. The majority of the patients with the clinical diagnosis of persistent generalized lymphadenopathy (PGL) were morphologically staged as FH or FF (89%), whereas most of the AIDS patients showed lymph node changes compatible with FA and FD (89%). Patients with AIDS-related complex (ARC) had a wider spectrum of morphological lymph node changes but a majority of cases (62%) were also classified as FA or FD. Clinical follow-up showed progression from PGL to ARC in seven of 21 cases with the FF pattern and only in three of 19 cases with FH, indicating a possible prognostic value in differentiating between FH and FF. Three cases with FD and one with FA progressed to AIDS during the time of observation. T4/T8 ratios in blood and lymph nodes were significantly lower in patients with FD histology compared to patients of the other histological groups. At autopsy, all AIDS cases showed the FD pattern of lymphadenopathy. Autopsy findings in seven patients emphasized the importance of post-mortem studies in clarifying the spectrum of opportunistic diseases, including tumors which afflict the AIDS patients.

AIDS-Related Complex↗