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Biomedical subjects

F Aiuti

Publications and source records attributed to F Aiuti.

At least 127 records · Page 7Linked to original sources

Complement activation is associated with the presence of specific human immunodeficiency virus (HIV)-anti-HIV immune complexes in patients with acquired immunodeficiency syndrome-related complex or lymphoadenopathy syndrome.

The complement system was examined in a group of eight patients (six with lymphoadenopathy syndrome (LAS); two with acquired immunodeficiency syndrome (AIDS)-related complex (ARC], who were found to be human immunodeficiency virus (HIV)-positive, for the presence of specific HIV-anti-HIV complexes. A significant impairment of the classical and/or alternative pathway was found associated with the presence of cleavage fragments of C3 and/or B and a significant reduction in the complement factors studied. Ultracentrifugation fractions of serum samples obtained from one of the patients were assessed for the detection of specific HIV-anti-HIV (GP41-anti-GP41) complexes and were incubated with normal human serum to determine their complement activation capacity. A clear complement activation was found with the fraction in which a clear peak of HIV-anti-HIV (GP41-anti-GP41) immune complexes was present. The results demonstrate that specific immune complexes and complement activation are sometimes concomitantly present in patients with AIDS-related disease and that specific immune complexes may be one of the causal factors of the pathogenesis of complement activation in these patients. Possible consequences for the severe immune regulation with relevance to the dramatic failure in treating the virus effectively are discussed.

AIDS-Related Complex↗

Alpha interferon treatment in HIV infected patients restores gamma interferon production in vitro.

We studied gamma interferon (IFN) production in vitro by lymphocytes from 5 patients with AIDS and 2 with advanced AIDS-related complex (ARC) before and during treatment with r-alpha 2a IFN at low doses, for up to 12 months. Patients were divided in responders (three) and non responders according to clinical data after six months of treatment. No immunological parameter was predictive of the clinical results. We found that subpopulations of T lymphocytes and lymphoproliferative response were not significantly modified in responders, while severely decreased in non responder patients. In 5/7 cases we observed a small but significant increase of gamma IFN production after six months of therapy, which rose to normal values after 12 months in responders.

AIDS-Related Complex↗

Retinal cotton-wool-like spots: a marker for AIDS?

The prognostic value of ocular manifestations and its correlation with immune changes in HIV-infected subjects was studied longitudinally with an average follow-up of one year (3-22 months). The most common ocular manifestations were retinal cotton-wool-like spots, observed in 58.8% of AIDS patients and in 76.9% of those with ocular involvement. Two of three ARC cases with cotton-wool-like spots developed Pneumocystis carinii pneumonia a few weeks after ophthalmoscopic examination. A close correlation between ocular changes and decrease of CD4+ lymphocytes was observed. In our opinion, these ocular manifestations are as useful as opportunistic infections or AIDS-related neoplasias in the natural history of HIV infection.

AIDS-Related Complex↗

Mechanism of defective natural killer cell activity in patients with AIDS is associated with defective distribution of tubulin.

Previous studies have demonstrated the importance of some cytoskeleton components in killing mechanisms. In fact, a microtubule and microfilament (MF) rearrangement in the lytic sequence of CTL and NK cells has been observed. In particular, MF seem to be related to the binding phase, because MF inhibitors suppress the binding of NK cells to the target, whereas microtubule inhibitors suppress only the killing phase. In this paper, the distribution of two cytoskeleton components, actin and alpha- and beta-tubulin, has been studied in PBL from AIDS patients, who maintain the capacity to bind to the target cell line K562 but are not able to kill it. PBL were labeled with mAb to these two cytoskeleton components, and then indirect immunofluorescence was used to visualize their distribution in the conjugates. A normal polarization of actin in the effector PBL was found, whereas no tubulin rearrangement was evident in the effector and target cells. On the contrary, in conjugates of PBL or large granular lymphocytes from normal donors and K562, a polarization of actin in the effector cell and a polarization of tubulin both in the effector and in the target cells, at the site of the attachment, was evident. These data suggest that a deficiency of tubulin rearrangement may underlie the inability of the NK cells from AIDS patients to kill their target.

Acquired Immunodeficiency Syndrome↗

Agenesis of the corpus callosum, combined immunodeficiency, bilateral cataract, and hypopigmentation in two brothers.

We describe 2 brothers with a malformation syndrome consisting of agenesis of the corpus callosum, cutaneous hypopigmentation, bilateral cataract, cleft lip and palate, and combined immunodeficiency. The clinical history of both patients was characterized by severe psychomotor retardation, seizures, recurrent severe respiratory infections, and chronic mucocutaneous candidiasis. The children died of bronchopneumonia at age 2 and 3 years, respectively. Immunological investigations showed, in one sib studied, skin anergy to recall antigens, profound depletion of T4+ lymphocytes, and serum IgG2 deficiency. Necropsy showed agenesis of the corpus callosum, hypoplasia of the cerebellar vermis, and profound hypoplasia of the thymus and of the peripheral lymphoid tissue. The distinctive features of these sibs appear to define a previously undescribed hereditary MCA/MR syndrome. The clinical and pathological findings seem to indicate, as a pathogenetic mechanism, a defect involving the embryonic organization of the central nervous system and of the immune system.

Abnormalities, Multiple↗

Diffusion of HIV-1 virus into non-habitual categories at risk in European countries.

The ECP Working Group on AIDS has evaluated the available data on seropositivity to HIV-1 supplied by research groups in 12 Eastern and Western European countries. The period covered is 1985 and 1986. A significantly elevated incidence of seropositives was observed in both females and males in heterosexual contact with members of high risk groups. In contrast heterosexuals with no such contact had an incidence below 1%. For male homosexuals from Italy, Denmark and Switzerland the trend was no detectable increase in prevalence from 1985 to 1986. Hungary and Poland now have a few per cent seropositive male homosexuals, but no seropositives were found in a group of Polish drug abusers.

Bisexuality↗

Evidence that defective gamma interferon production in patients with primary immunodeficiencies is due to intrinsic incompetence of lymphocytes.

We have selected 11 patients with primary immunodeficiency disorders predominantly affecting T lymphocyte function (four with ataxia-telangiectasia (AT), four with common variable immunodeficiency (CVI) and one each with Wiskott-Aldrich syndrome, hyper-IgE syndrome and combined immunodeficiency) with defective gamma interferon (IFN-gamma) production in vitro. Induction with phytohaemagglutinin showed low interleukin 2 (IL-2) production concomitant with reduced IFN-gamma titres. However the addition of 10 U/ml of rIL-2 to cultures stimulated with staphylococcal enterotoxin B or galactose oxidase failed to restore IFN-gamma production in defective cases. IFN-gamma was titrated by both bioassay and immunoradiometric assay, ruling out the possible release of inactive or altered IFN-gamma molecules. Normal levels of IFN-gamma were found in patients of patients with AT, as well as in two AT and two CVI cases, demonstrating heterogeneity of defects within these syndromes. Soluble inhibitors or cellular suppression of IFN-gamma were not observed in mixing experiments. The possibility that defective interaction between accessory cells and T lymphocytes might account for the poor response to the inducing agents was ruled out as no IFN-gamma was produced using a calcium ionophore--which bypasses this step--in seven patients with absolute IFN-gamma deficiency.

Ataxia Telangiectasia↗

Passage of food antigens into circulation of breast-fed infants with atopic dermatitis.

We have selected 13 babies presenting with atopic dermatitis during exclusive breast feeding. After evaluation of reaginic reaction, we detected beta-lactoglobulin (BLG) in breast milk and babies sera before and after maternal elimination diet and after maternal challenge. beta-Lactoglobulin was present only in the sera of infants ingesting breast milk containing BLG. We have seen reaginic reactions to cow's milk in seven babies. The maternal elimination diet improved eczema in 11/13 infants, maternal challenge worsened atopic dermatitis in 9/9 children. We demonstrated the transport of food antigen via breast milk into infants' circulation.

Breast Feeding↗

Natural killer activity from normal peripheral blood lymphocytes against a human T lymphotropic retrovirus type III (HTLV-III)-infected cell line.

An H9-HTLV-III-infected cell line was used as a target in a short-term (3-hr) Cr release assay to assess its sensitivity to lysis by peripheral blood lymphocytes (PBL) from normal donors. The single cell cytotoxicity assay (SCCA) on poly-L-lysine-coated coverslips was used to investigate further the mechanism of binding and killing. Uninfected H9 and K562 cell lines were studied as controls. Our results argue in favour of a natural killer (NK) mechanism being operative on an H9-HTLV-III-infected cell line owing to the following findings: (1) the cell line is sensitive to lysis in a short-term assay; (2) its sensitivity is significantly higher than K562; and (3) the kinetics of lysis, as assessed by SCCA, is similar to that of K562, with a more efficient killing being detectable against H9-HTLV-III. Furthermore, a phenotypic analysis of effector cells suggests that CD4+ lymphocytes are also involved in the lysis of this target. Our data provide evidence for an immune mechanism that may be operative in HTLV-III infection. We then studied, by this method, five groups of patients: one (n = 20) affected by acquired immunodeficiency syndrome (AIDS), one (n = 20) by AIDS-related complex (ARC), one (n = 20) by lymphadenopathy syndrome (LAS), one group (n = 40) of HTLV-III seropositive, apparently healthy people, and one (n = 40) of healthy HTLV-III seronegatives.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Complex↗

Studies on the in vitro effects of auto-anti-IgE. Inhibition of total and specific serum IgE detection by a human IgG autoantibody to IgE.

We isolated a human IgG anti IgE autoantibody by affinity chromatography on a myelomatous IgE (N.D.) coated Sepharose column, from the serum of a patient with atopic eczema, and probed its ability to inhibit IgE recognition by heteroantisera to IgE used in commonly available assays for serum total and specific IgE determinations (Paper radio-immunosorbent test--PRIST and Phadezym radioallergosorbent test--RAST, both from Pharmacia, Uppsala--Sweden). Our results indicate that IgG anti IgE decrease total IgE results by 10-90% according to its weight ratio to IgE molecules present in samples devoid of endogeneous anti-IgE. Sera with high content of specific IgE to house dust mite (RAST class 3 or 4) are less affected by this autoantibody, but RAST class 2 may be significantly lowered when purified IgG anti IgE is added. These data imply that anti IgE can affect both total and specific IgE determinations.

Allergens↗

Retinal cotton-wool-like spots: a marker for AIDS?

The prognostic value of ocular manifestations and their correlation with immune changes in HIV-infected subjects (75 PGL, 23 ARC, and 17 AIDS) have been longitudinally studied with an average follow-up of one year (3 to 22 months). The most common ocular manifestations were retinal cotton-wool-like spots, observed in 58.8% of AIDS patients and in 76.9% of those with ocular involvement. Two of three ARC patients who showed cotton-wool-like spots developed PCP a few weeks after ophthalmoscopic examination. A close correlation between ocular changes and decrease of CD4+ lymphocytes was observed. In our opinion, these ocular manifestations are as useful an indicator as opportunistic infections or AIDS-related neoplasias in the prognosis of HIV infection.

AIDS-Related Complex↗