[AIDS--will we have an effective vaccine?].
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Biomedical subjects
Publications and source records attributed to Z T Handzel.
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We have used ELISA to study the frequency of autoantibodies to several antigens in the serum of 17 male homosexuals (MHS) negative for HIV (HIV-), 11 asymptomatic HIV seropositive MHS (HIV+) and patients with ARC (N = 15) or AIDS (N = 13), and compared them to 20 matched healthy heterosexual controls. Serum antibody binding to histones, cardiolipin, ss-A, ss-B and Sm was found to be significantly higher in each of the MHS groups studied as compared to controls (P less than 0.001), and was also increased in the HIV+ patients vs. the HIV- group (P less than 0.05). In contrast, no increase in autoantibodies to ss-DNA, ds-DNA, poly(I), poly(G) or RNP were found in any of the groups tested. These results enlarge the spectrum of autoimmunity previously reported in HIV infection and identify a similar pattern to a lesser degree, already present in HIV- MHS, suggesting a role for HIV or concomitant virus infections in its pathogenesis.
High rates of immunologic abnormalities in asymptomatic, clinically healthy urban homosexual men have been associated with promiscuous, unprotected receptive rectal intercourse, and related to infection by the human immunodeficiency virus (HIV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cohort studies in Israel, which is still a low risk country for HIV infection and AIDS, about 40% of asymptomatic, clinically healthy male homosexuals consistently showed T cell defects that were not correlated with anal-receptive sexual behavior and were independent of HIV antibody status. Since pre-existing immune impairments in HIV-seronegative individuals have been implicated as a risk factor for seroconversion, we have attempted to investigate more precisely the role of anal-receptive homosexual activity as a risk factor for the acquisition of immune defects. We compared T lymphocyte profiles and mean geometric titers of EBV and CMV in a homogeneous group of 14 transvestite and male anal-receptive homosexual prostitutes with those of 77 HIV-seronegative male homosexuals who were not exclusively anally passive with multiple sex partners. While 44% of the control group showed a decrease of total T cells or their subpopulations as compared with normal heterosexual men (P less than 0.001), T lymphocyte values of the anal-receptive prostitutes were within the normal range. In the prostitutes, serum antibodies to HIV were detected in only 1 individual, to CMV in 12 of 13, and to EBV in all. Despite high mean geometric titers of antibodies to CMV (86.6) and EBV (25.8), frequent anal-receptive intercourse was not sufficient, in itself, to cause immune impairment in this unique group. The results suggest that the problem of cofactors contributing to immune deficiency in male homosexuals should be reexamined in countries with a low incidence for HIV seropositivity and AIDS.
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In an attempt to assess the role of immune cytotoxic activity in the sequence of events leading to the acquired immunodeficiency syndrome (AIDS), natural cytotoxic activity was studied in 17 asymptomatic homosexual males, seropositive for anti-human immunodeficiency virus (HIV) antibodies, as compared to 16 of their seronegative counterparts and to 14 control healthy heterosexual individuals. Cell (contact)-mediated cytotoxicity (CMC) as well as cytotoxin (CTX) production by lipopolysaccharide (LPS)-stimulated, phytohemagglutinin (PHA)-stimulated, HeLa tumor cell-stimulated, and unstimulated peripheral blood mononuclear cells (PBMC) were determined using HeLa cell monolayer cultures, sensitized with cycloheximide, as targets. The CMC was markedly enhanced in the seropositive group (28 +/- 21 (mean +/- SD) lytic units/10(6) PBMC) as compared to the seronegative group (17 +/- 7; P less than 0.005) and to the heterosexual group (13 +/- 6; P less than 0.05). Likewise, CTX production by unstimulated PBMC from seropositive homosexuals (19 +/- 26 units/ml) was higher than that observed in the other groups (both 4 +/- 4 units/ml; P less than 0.05). CTX production by PHA-stimulated, LPS-stimulated, and HeLa cell-stimulated PBMC was significantly enhanced in both the seropositive and seronegative groups in comparison to the normal heterosexual controls. These results suggest that increased cytotoxic activity may be present in homosexuals prior to their exposure to HIV, and may be further enhanced after HIV infection.
Antigens of armadillo-derived Mycobacterium leprae sonic extract were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotted onto a nitrocellulose membrane, and the unstained blot was converted into 20 fractions of antigen-bearing particles. These were tested in cellular proliferation assays, and reproducible results were obtained between batches of fractions. Peripheral blood mononuclear cells from healthy contacts of leprosy patients (presumed to have protective immunity) were tested with the fractions to investigate which antigens they recognized. A small group of tuberculoid leprosy patients were also tested. Both groups showed a wide range of responses. Almost every fraction stimulated proliferation with at least one donor, yet none was clearly immunodominant or inhibitory in either group. Thus, protective immunity did not appear to be associated with proliferation caused by any single fraction.
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Human immunodeficiency virus (HIV 1) strains were isolated from peripheral blood lymphocytes of eight homosexual men (two asymptomatic and six with lymphadenopathy syndrome) and of the wife of an AIDS patient with AIDS-related complex. All except one had antibodies to HIV in their serum. Virus isolation was carried out by cocultivation of the donors' peripheral lymphocytes with HUT-78 cells or with phytohemagglutinin-stimulated normal cord blood lymphocytes. Identification of the virus was based on detection of specific cytopathogenic effects, determination of reverse transcriptase activity, specific immunofluorescence and Southern blot analysis of HIV proviral DNA in the infected cell cultures.
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We have studied 288 Israeli asymptomatic male homosexuals (MHS) to determine the prevalence of antibodies to HTLVI and HTLVIII and their correlation with impairments of the immune system and serum interferon (IFN). Seropositivity for HTLVI, HTLVIII, or both was found in 1.4, 8.3, and 0%, respectively. Significant decreases in the total peripheral T cells, TH cells, and TH/TS ratio as well as elevated alpha IFN serum levels were found in the MHS group in comparison with normal controls. Although no difference in the prevalence of either immune derangements or elevated serum IFN was observed between HTLVIII/LAV-seropositive and HTLVIII/LAV-seronegative MHS, the decreases in total T cells, TH cells, and TH/TS ratios were significantly greater in the seropositive MHS. These results indicate that (a) immune impairments and IFN system activation occur commonly in homosexuals, precede their exposure to HTLVIII/LAV, and probably reflect this group's increased risk for AIDS and (b) HTLVIII/LAV infection of MHS aggravates further their preexisting immune impairments.
The feasibility of using Thymic Humoral Factor (THF) for immunomodulation in asymptomatic male homosexuals was evaluated in a study on fifteen subjects with T-cell impairments, selected on the basis of a 2SD reduction in T helper/inducer (T4+) cells and one additional lymphocytic defect. Following two biweekly courses of treatment, mean relative increments of T4+ (P less than 0.002), T3+ (P less than 0.02) and total lymphocyte (P less than 0.05) populations of the group receiving THF (n = 7) were significantly increased when compared to the placebo group (n = 8). In addition, a transient increase in T4+ lymphocytes was observed after the first course in the two individuals of the THF-treated group who were seropositive for HTLV-III/LAV but not in those who were seronegative. No difference was found between the groups in fluctuations of serum interferon (IFN) or proliferation of peripheral mononuclear cells to mitogens. The results of this limited trial demonstrate that THF is capable of correcting T-cell impairments that may predispose asymptomatic homosexuals to infection by HTLV-III, without affecting IFN production. These findings suggest that future strategies for AIDS prevention in high-risk groups should include institution of large controlled trials in immunodeficient, asymptomatic, HTLV-III/LAV-seronegative male homosexuals to study the potential of selective immunoreconstitution as a preventive measure against HTLV-III/LAV infection.
Five infants with congenital immune defects are presented. Three had various combined immune deficiencies (CID) and two had thymic deficiencies only. As bone marrow or thymus transplantations were not feasible in these patients, we attempted treatment with thymic humoral factor (THF), a thymic hormone, by daily i.m. injections during biweekly courses. In one CID patient, a partial improvement in immune indices and temporary clinical improvement were achieved. In the other two, THF did not arrest the patients' demise. The two patients with thymic dysplasia benefitted repeatedly from THF treatment, as exemplified by the disappearance of wasting, diarrhea and infections and by reconstitution of T cell parameters. Nevertheless, the patients relapsed after prolonged periods without THF administration. We therefore propose the administration of long-term, continuous or intermittent thymic hormone replacement therapy in infants with congenital thymic defects. Early diagnosis and immediate institution of treatment will probably improve prognosis.
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More than 50% of a group of healthy homosexuals in Israel were found to have an activated interferon (IFN) system as evidenced by markedly elevated blood IFN levels, increased in vitro production of IFN by unstimulated peripheral blood mononuclear cells and HuIFN-alpha and HuIFN-gamma production by appropriately stimulated cells, and a surprisingly high incidence of an antiviral state of cells. This pattern resembles that found in persons with acute viral illness, and is unlike that found in normal healthy controls. The type of IFN in the blood was found to be unusual in that it was mainly HuIFN-alpha, pH 2-labile, a type of IFN found in certain collagen diseases as well as in homosexual men suffering from Kaposi's sarcoma or lymphadenopathy. Natural killer (NK) cytotoxic activity was found to be somewhat lower than that found in normal controls, although no correlation was found between blood IFN levels and NK activity. Mean (2'-5')-oligoisoadenylate synthetase levels in cell extracts were intermediate between normal controls and patients with viral illness. Likewise no correlation was found between enzyme levels and blood IFN levels. The highly activated IFN system found in certain homosexuals, as well as the increased spontaneous production of IFN by unstimulated mononuclear cells, suggest the possibility of the presence of a virus, active or latent, in these individuals. This virus could be a retrovirus such as HTLV-III or LAV which have recently been isolated from AIDS patients. The special type of IFN present could be the response to a novel virus in an unusual situation. On the basis of recent reports, we speculate that homosexuals with highly activated IFN systems who produce pH 2-labile HuIFN-alpha could be at increased risk for developing AIDS.
Noma is an uncommon gangrenous process usually affecting malnourished children. A full-term neonate with orofacial noma, bilateral choanal atresia, and transient neutropenia with B cell deficiency is reported. This unusual appearance of noma in a well-nourished newborn might be related to the combination of choanal atresia and transient immune deficiency.