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Biomedical subjects

F Aiuti

Publications and source records attributed to F Aiuti.

At least 145 records · Page 8Linked to original sources

Immune response to cytomegalovirus in patients with acquired-immunodeficiency syndrome related complex (ARC) and AIDS.

This study was undertaken with the aim of elucidating the mechanisms underlying the cell-mediated immunodeficiency seen in the acquired immunodeficiency syndrome (AIDS). An intrinsic functional defect in the in vitro surviving T lymphocytes from patients with AIDS has been described. This defect is reflected by profound reductions in both the cloning efficiency of these cells and in the number of precursor cells for response to lectins. Since many patients affected by AIDS present active cytomegalovirus (CMV) infections and impairment in CMV-specific cellular immunity, we examined the number of CMV-specific precursor cells in patients affected by the AIDS-related complex (ARC), who had serum antibodies to CMV and to the human-T-lymphotropic retrovirus-type III (HTLV-III), recently termed human immunodeficiency virus (HIV). Their responses were compared to those of patients with AIDS and to those of healthy-CMV-seropositive and HTLV-III seronegative controls. We detected a significant reduction of precursors for cell-mediated immune response to CMV in AIDS, in comparison to normal controls and a reduction in ARC, even if not significant. In parallel, we assayed the response to phytohemagglutinin, which was maintained in ARC and depressed in AIDS. Our results show a defect of specific cell-mediated immunity to CMV in ARC and AIDS patients.

AIDS-Related Complex↗

Characterization of specific immune complexes in HIV-related disorders.

Eighty-seven seropositive subjects with HIV (human immunodeficiency virus) infection together with 20 normal controls with no history of any illness were investigated for the presence of circulating immune complexes (CIC) by the conglutinin binding assay (KgBA) and further studied for isotype characterization of CIC. Six out of 87 patients showing very high values for immune complexes (CIC) were studied for the presence of free antigen. In 3 out of 6 (1, IVc1; 1, III; 1, IVa) we could detect by ultracentrifugation analysis the presence of specific HIV (p15) anti-HIV (anti-p15) and gp41-anti-gp41 CIC. Evidence in favour of this finding is supported by: the presence of specific CIC (p15-anti-p15 or gp41-anti-gp41) seen only at pH 7.2; the apparent presence of free antigen and specific HIV antibodies were only at pH 4.0. The relevance of this finding lies in the attempt to explain the occurrence of false seronegativity seen occasionally in symptomatic patients. Thus, the presence of CIC might perhaps interfere in the routine assay (i.e. ELISA) making the diagnosis difficult. All these considerations will have to be taken into account in the future handling of this disease.

Acquired Immunodeficiency Syndrome↗

Evaluation of the presence of RF-like activities in immunoglobulin preparations for intravenous use. I. IgG anti-IgE in intravenous Ig.

We have studied the IgG anti-IgE antibody content of 8 IgG preparations for intravenous administration that we use in our Day Hospital as replacement therapy for patients with hypogammaglobulinemia. In all preparations we found the presence of both IgE and IgG anti-IgE as monomers and oligomers after fractionation with ultracentrifugation on sucrose gradient. This RF-like activity seem to be an essential constituent of low m.w. aggregates, disappearing at acid pH. We suggest that its presence could be responsible for the enrichment of IgE in Ig preparations for therapeutic use and perhaps for immediate and long-term adverse reactions.

Antibodies, Anti-Idiotypic↗

Clinical immunology of immunodeficiency diseases symptoms and signs of primary immunodeficiencies.

This article gives a general overview of the signs and symptoms observed in primary immunodeficiencies (PID). These diseases, although rare, are useful in the understanding of the specific functions and properties of the immune system. Emphasis has not been placed on the biological and laboratory features since the principal goal is to describe the clinical approaches for a correct diagnosis in this group of diseases. Schematic indications of therapy are given only in single diseases, when necessary. The report and the classification are organized according to the more recent recommendations of a Special WHO-Committee for Primary Immunodeficiencies.

Humans↗

Immune complexes in food-induced arthralgia.

Ten patients are described who, in addition to other allergic symptoms, suffered from arthralgia. Dietary exclusion relieved the symptoms and specific food challenge reproduced them. IgG anti-IgE autoantibodies were high in patients with arthralgia in the serum and in the synovial fluid as compared with normals and the majority of patients with rheumatoid arthritis, traumatic arthralgia, and osteoarthritis used as controls. In three food-allergic patients IgG anti-IgE was detectable in a complexed form in the serum samples examined before and after food challenge. The finding of IgG anti-IgE autoantibody in a group of patients with allergic arthralgia is quite exciting. It raises the possibility of distinguishing a subgroup of arthralgic patients not having a classical rheumatoid arthritis, who may have a definable external exacerbating cause for their symptoms. A larger detailed survey is now in progress.

Adult↗

Evidence for activation of complement in patients with AIDS related complex (ARC) and/or lymphoadenopathy syndrome (LAS).

The complement system was examined in 16 patients with AIDS-related complex (ARC) (n = 5) and/or lymphoadenopathy syndrome (LAS) (n = 11). Of these patients 62.5% showed an impairment of classical and/or alternative pathway activity associated with the presence of cleavage fragments of C3 and/or B and a significant reduction of many complement factors. The data indicate pathological complement activation in these patients through the classical and/or alternative pathway. Complement activation was more severe in patients with ARC than in those with LAS, and greater in drug abusers than homosexuals. The lack of efficient complement in the patients can be considered an 'acquired complement deficiency' with possible importance in the failure to combat the HIV attack.

AIDS-Related Complex↗

Detection and characterization of circulating immune complexes in HIV-related diseases.

Using an ultracentrifugation technique human immunosuppressive virus (HIV) (GP15 and GP41), anti-HIV (anti-GP15 and anti-GP41) immune complexes were detected in the sera of 3 (1 Acquired immune deficiency syndrome (AIDS), 1 AIDS related complex (ARC), 1 Lymphadenopathy syndrome (LAS] out of 6 patients studied. Evidence for presence of HIV immune complexes was provided by: 1) demonstration of GP15 anti-GP15 and GP41 anti-GP41 immune complexes at neutral pH (pH 7.2); and 2) presence of free HIV antigen and specific HIV antibodies after dissociation of immune complex-like material with acid buffer. Formation of specific immune complexes in the sera of AIDS and ARC patients may be responsible for failure to detect free HIV antibodies in some of these patients.

AIDS-Related Complex↗

Phenotypically immature IgG-bearing B cells in patients with hypogammaglobulinemia.

We investigated the prevalence of phenotypically immature IgG B cells (i.e., coexpressing surface IgG and IgM) in the peripheral blood of 12 patients with hypogammaglobulinemia and in normal individuals. Patients had ataxia-telangiectasia (N = 1), hyper-IgM combined immunodeficiency (N = 1), or common variable immunodeficiency (CVI). IgG/IgM-positive B cells were evaluated by two-color immunofluorescence using fluorescein- or rhodamine-conjugated goat antiserum; to minimize artifacts due to in vivo cytophilic binding of autologous IgG, cell-bound cytophilic Ig were eluted at pH 4 and Fc receptors were blocked by heat-aggregated rabbit IgG before fluorescent staining. All patients, except two with late-onset CVI, had markedly increased proportions of double-stained IgG B cells (56 to 100% of IgG-bearing B cells) in comparison with normal individuals (11 to 33%).

Adult↗

Results in two infants with the DiGeorge syndrome--effects of long-term TP5.

We treated two patients affected by DiGeorge syndrome with long-term administration of the synthetic thymic hormone thymopoietin (TP5). In both cases we obtained durable immunological reconstitution, starting as early as 2 weeks after beginning of TP5 treatment. High levels of circulating immature thymocytes and precursor T cells (defined by monoclonal antibodies OKT6, OKT9, and OKT10) were present prior to therapy, and they steadily decreased during the first few weeks of study. During the same time, phenotypically mature T lymphocytes (OKT3+ and OKT4+/OKT8+) markedly increased, thereafter remaining at near normal levels. OKT10+ cells appeared to rise again after 3 months of TP5 treatment. In vitro function of T cells, assessed by PHA stimulation, and in vivo cell-mediated immunity (skin tests with Candida) were normal at 3 and at 2 months, respectively, after initiation of therapy. No severe infection episodes were recorded and normal development was achieved. No side effect or adverse reaction occurred. In these two patients the other features of the DiGeorge syndrome were successfully treated by early cardiac surgery and vitamin D therapy. The immunological reconstitution, in absence of functioning thymus observed in these two cases, provides further evidence of the effectiveness of long-term treatment with thymic hormones--with maintenance of the improvement of cell-mediated immunity.

Antibodies, Monoclonal↗

Hypogammaglobulinemia with hyper-IgM, severe T-cell defect, and abnormal recirculation of OKT4 lymphocytes in a girl with chronic lymphadenopathy.

We describe here one 8-year-old girl with an unusual form of immunodeficiency, characterized by hypogammaglobulinemia with hyper-IgM, severe T-cell defect, and chronic lymphadenopathy. Patient's B cells failed to produce IgG or IgA in vitro following stimulation with either pokeweed mitogen or Epstein-Barr virus, suggesting an intrinsic B-cell defect. Abnormal T-cell function was demonstrated by impaired in vivo delayed type hypersensitivity, reduction of mitogen-induced proliferation and interleukin 2 production, reduction of interferon-gamma production, and marked decrease of circulating OKT4+ cells. The latter cells were found in normal proportion in the patient's lymph node tissue. This finding suggests that the decrease of OKT4+ cells in peripheral blood was due to the abnormal recirculation of these cells. The identity of this syndrome with the infantile form of the acquired immunodeficiency syndrome was apparently ruled out by the failure to demonstrate HTLV-III-related sequences in patient's lymphocytes or virus-specific serum antibodies.

Agammaglobulinemia↗

Deficiency of natural killer activity, but not of natural killer binding, in patients with lymphoadenopathy syndrome positive for antibodies to HTLV-III.

Blood lymphocytes (BL) of eleven patients with lymphoadenopathy syndrome (LAS) were studied for natural killer (NK) activity against the K562 cell line (using both the standard 51Cr release assay and the single-cell cytotoxicity assay on poly-L-lysine-coated coverslips) and for surface phenotype (employing OKT4, OKT8 and Leu7 monoclonal antibodies). A significant reduction in NK activity and in NK active cells was detected, while the percentage of target binding cells was not affected. Furthermore, the OKT4/OKT8 ratio was found to be inverted, and the Leu7+ subpopulation expanded. The patients had high titers of anti-HTLV-III antibodies. This study indicates that defective NK activity in LAS is secondary to an abnormality in the lytic event itself and not in target binding.

Adult↗

Direct and cell-mediated effects of interferon-alpha and -gamma on cells chronically infected with HTLV-III.

The replication of the human T lymphotropic retrovirus HTLV-III in persistently infected cells is relatively insensitive to the direct antiviral action of human interferon-alpha or -gamma (IFN-alpha or -gamma), showing only a two- to threefold reduction of HTLV-III, even though the host cells are very sensitive to IFN, as shown by vesicular stomatitis virus (VSV)-yield reduction assay (4-5 log reduction of VSV). However, IFN anticellular activity is strongly enhanced in the presence of normal peripheral blood mononuclear cells, suggesting a cell-mediated effect of IFNs.

Acquired Immunodeficiency Syndrome↗

IgG anti-IgE in circulating immune complexes in the hyper-IgE syndrome.

We fractionated, by gel chromatography, sera with high IgE content from atopic subjects and five cases with the hyper-IgE syndrome, and measured the presence of IgE in high molecular weight (HMW) fractions. Two out of four asthmatics and four out of five hyper-IgE had HMW IgE. The same serum fractions gave positive results for conglutinin binding IgG (all six) and IgA (three cases) as well as C1q binding complexes (five cases). IgG auto-antibodies to IgE were also detected together with IgE in HMW fractions. Anti-F(ab)'2 activity was present in five cases (one of them negative for IgG anti-IgE). Our data indicate that complexes made of IgE and IgG anti-IgE are present mainly in patients with chronic allergic symptoms and most frequent in cases of hyper-IgE syndrome.

Antibodies↗

A study of IgE in immunoglobulin preparations for intravenous administration. I. IgE in intravenous IgG.

We have studied the IgE content of different lots of commercial intravenous IgG preparations used in our day hospital as replacement therapy for patients with agammaglobulinemia. Two enzymatic methods were used: Phadezym and FAST. The average amounts of IgE detected in Endobulin and Sandoglobulin lots were very high with respect to serum values in the general population. In some lots we found low titers of specific IgE (RAST class 1) to house dust mite, rye grass and cow's milk. We also found in most preparations the presence of IgG anti-IgE which are usually present in sera from atopic patients. Despite a low post-infusion increase of serum IgE and the absence of sensitization or adverse reactions observed, a careful selection of donors with normal IgE levels may need to be recommended to manufacturers in the future.

Agammaglobulinemia↗