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Biomedical subjects

F Aiuti

Publications and source records attributed to F Aiuti.

At least 217 records · Page 12Linked to original sources

Monoclonal antibody analysis of T cell subsets in 40 patients with immunodeficiencies.

A panel of previously characterized monoclonal antibodies: OKT3, OKT4, OKT8, OKT10, OKT11, OKIa1, OKM2; 3A1, 4F2, UCTH1 and 5/9 were used to evaluate peripheral blood mononuclear cells in patients with severe primary immunodeficiencies: three patients with severe combined immunodeficiency, five with X-linked agammaglobulinemia, 20 with common variable hypogammaglobulinemia, 11 with IgA defect, and one with an unclassified form of T cell defect and hypogammaglobulinemia. Surface markers for T and B cells and in some cases functional assays, were also performed. Our results indicate a heterogeneous pattern in patients with severe combined immunodeficiency: one had peripheral blood mononuclear cells negative with all the monoclonal antibodies used; one had an increase in OKM2+ cells, whereas OKT3+ cells were absent; one had defect and imbalance of immunoregulatory T cell subpopulations. Major imbalances of T cell subsets were not detected in patients with X-linked agamma and IgA defect, whereas in some patients with common variable hypogammaglobulinemia an inversion of the physiological ratio between OKT4+ and OKT8+ cells was consistently detected. In an unclassified case of primary immunodeficiency, almost all peripheral blood mononuclear cells formed rosettes with sheep erythrocytes, but lacked antigens detected by monoclonal antibodies. Based on these observations, possible sites of defects in the T cell differentiation are discussed. We believe that monoclonal antibodies are useful for diagnosis, classification, and monitoring of therapy of primary immunodeficiencies.

Adolescent↗

Enhancement by TP-1, a thymic extract, of pokeweed mitogen-induced differentiation of B cells from normal subjects but not of those from patients with systemic lupus erythematosus.

We studied the ability of TP-1, a calf thymic extract, to influence in vitro pokeweed mitogen (PWM)-induced plasma cell generation and blastogenesis of peripheral blood lymphocytes from normal donors and from patients with systemic lupus erythematosus (SLE). In normal subjects, TP-1 significantly increased plasma cell generation, but did not affect the mitogenic response to PWM. On the contrary, differentiation of B cells from SLE patients was not enhanced by this extract. The action on the differentiation of normal B cells could either be due to a direct effect on B cells or be mediated by activation of helper T cells.

Animals↗

Immunologic evaluation of T chronic lymphocyte leukemia cells: correlations among phenotype, functional activities, and morphology.

Chronic lymphocytic leukemia of T-cell origin (T-CLL), a rare variant of CLL, appears to be a clonal proliferation of mature T cells of one of several subsets. In the cells of 7 T-CLL patients, surface markers (including those reacting with a panel of monoclonal antibodies), functional activities, and electron microscopic morphology were evaluated. The phenotypic patterns of circulating T-CLL cells correspond to those of normal mature T-cell subsets. The cells of three patients demonstrated at least one marker reported to be expressed by suppressor/cytotoxic T cells: those of three patients expressed markers apparently linked with T-helper activity. Cells from one patient appeared to be a heterogeneous proliferation of more than one T-cell subset. These T-CLL cells may also retain some of the functional activity of the normal T subpopulations. Our data indicate that a combination of several tests should be used to characterize the proliferating cells in T-CLL.

Aged↗

T-dependent immunity in aged humans. I. Evaluation of T-cell subpopulations before and after short term administration of a thymic extract.

T lymphocytes, T lymphocyte subpopulations and delayed hypersensitivity reactions to recall antigens were studied in 20 aged subjects clinically unaffected by disorders of the immune system. T-cells evaluated by the sheep rosette test and absolute T-cell number were within normal range. T-cell subsets were studied by the high affinity rosetting test and by the sheep rosette test after pre-incubation with theophylline; such methods have been shown by others to discriminate between T-cells with helper or suppressor activity. We did not observe an imbalance of such subpopulations. Skin reactivity to recall antigens (Candida and SK-SD) was depressed in several cases. Since a decline in serum levels of thymic hormones has been reported in the ageing and it is suggested that this could account for the T-dependent immunity defect, we treated these patients with a bovine thymic extract (thymostimulin, TP-1) 1 mg/kg/day for three consecutive days. Immunological tests were performed again after this therapy but no modifications were observed. We may conclude that the aged subjects studied in this paper present normal relative and absolute number of T-cells and T subpopulations, whereas the function of T-cells, as assessed by skin reactivity to recall antigens is often depressed. Short term therapy with TP-1 at the above mentioned dosage was ineffective in modifying the parameters analysed.

Aged↗

A child with atopic features, raised serum IgE, and recurrent infection treated with levamisole.

A 6-year-old girl had a long history of severe eczema, asthma, recurrent otitis media, and staphylococcal infections with disseminated chronic skin abscesses. Immunological studies showed a neutrophil chemotaxis defect, hyperimmunoglobulinaemia E, IgE antibodies against cows' milk proteins, absence of IgM, and absence of staphylococcal haemolysins. Neutrophil phagocytic and bactericidal functions and complement system were normal. In the course of treatment with levamisole (2.5 mg/kg, 3 times a week for one year) a striking clinical improvement occurred: the skin lesions and the staphylococcal abscesses gradually cleared and the girl gained weight. There was also a partial correction of the immune deficiency.

Abscess↗

Imbalances of T cell subpopulations in primary immunodeficiencies and systemic lupus erythematosus.

In the present report we describe a recently proposed technique for the enumeration of T lymphocyte subpopulations. The study was performed on peripheral blood lymphocytes (PBL) of 21 patients with primary immunodeficiencies and 10 with systemic lupus erythematosus (SLE). With this methodology, sheep rosettes are evaluated before and after preincubation with theophylline. Previous reports have shown that cells rosetting after the preincubation (T-res) contain most of the percentages of the helper activity, whereas sensitive cells (T-sens) exert suppression. T-res and T-sens cells were compared to several clinical and immunological parameters, including the detection of lymphocytes with Fc IgM and IgG receptors. We demonstrated a significant positive correlation between T-res and and EAox IgM cells and between T-sens and EAox IgG cells. In addition, patients with Ig defects demonstrated heterogeneity regarding alterations in the proportions of T-res and T-sens cells. On the contrary, in 8 patients with SLE, there was a markedly reduced proportion of T-sens cells. Variations in the balance of subpopulations were observed after treatment with thymic hormones and levamisole. We may conclude that theophylline rosettes represent an easy technique that can be profitably used in the evaluation of T cell subpopulations in immunological diseases.

Adult↗

Circulating immune complexes detected by C1q solid phase assay in leprosy.

Sixty-three sera of patients with leprosy were tested for the presence of circulating immune complexes (CIC) by C1q solid phase assay (C1qSPA). The mean values in CIC levels in leprosy patients were very high in comparison to native and European controls. No difference was found in the tuberculoid and lepromatous forms, but there was a good correlation between the presence of CIC and autoantibodies.

Adolescent↗

Formalin-treated bacteria as selective B cell mitogens: results in primary and acquired immunodeficiencies.

The mitogenic activity of the formalin-treated bacterial strains Branhamella catarrhalis, Haemophilus influenzae and the Cowan I strain of Staphylococcus aureus was assessed in peripheral blood lymphocytes (PBL) from patients with primary immunodeficiencies, acute lymphocytic leukaemia (ALL), chronic lymphocytic leukemia (CLL) and in umbilical cord blood lymphocytes. The bacteria selectively stimulated B cells, as demonstrated by the finding of a normal de novo DNA synthesis in children with a T cell defect and of an absent response in X-linked agammaglobulinaemia and severe combined immunodeficiency. A decreased mitogenic activity was exerted on PBL from four out of seven adults with common variable hypogammaglobulinemia (CVH). In B-CLL the mitogenic activity was normal while in T-ALL it was decreased. Umbilical cord blood lymphocytes responded better than PBL from adults. The selective stimulative ability of the bacteria for B lymphocytes is expressed when PBL are cultured together with the formalin-treated bacteria for 48 to 72 hr.

Adolescent↗

Improvement of natural killer activity and of T cells after thymopoietin pentapeptide therapy in a patient with severe combined immunodeficiency.

The case of an 18-month-old child, affected by malnutrition, severe interstitial pneumonia and immunological abnormalities is reported. Since the age of 10 months, the infant suffered from severe recurrent infections and failure to thrive. Immunological studies revealed a striking decrease of T lymphocytes and of natural killer (NK) function. Serum immunoglobulins, salivary IgA, natural isohaemagglutinins, Fc-IgG receptor-bearing cells and suppressor T lymphocytes were absent, together with an impaired de novo DNA synthesis after PHA, Con A, PWM and Cowan I strain from Staphylococcus aureus stimulation. In vitro incubation of the patient's lymphocytes with TP-5, a thymopoietin-derived synthetic pentapeptide, resulted in improvement of sheep rosettes, Fc-IgG receptor-positive lymphocytes and NK activity. The child was therefore treated with TP-5 for 8 months and his clinical condition improved as well as the number of T cells, Fc-IgG-positive lymphocytes and NK function. However, humoral immunity remained persistently depressed. We suggest that this child could be classified as affected by 'late-onset severe combined immunodeficiency'. In vitro assays with thymic hormones or synthetic drugs that mimic the action of thymic hormones should be performed and this therapy could be applied in the treatment of some of these heterogeneous syndromes, especially when an immunological reconstitution with bone marrow or fetal graft cannot be attempted.

Antigens↗

[Clinico-immunological studies of 32 cases of bone tumors].

We have studied 32 patients with different bone neoplasias. 18 had osteogenic sarcoma. Clinical and immunological observations led us to consider our results as a general approach to the problem. No specific conclusions can be made. We describe 3 patients treated with levamisole therapy and two with transfer factor. In single patients some useful observations are connected about relationship between treated and non-treated patients.

Adolescent↗

IgA deficiency and circulating immune complexes in Neapolitan children with fatal acute respiratory infections.

Immunoglobulins, C3 and C4 levels and circulating immune complexes have been measured on admission sera from 34 children admitted to a Naples hospital during the winter of 1978/79 with severe, usually fatal, acute respiratory infections and in age-matched controls from Rome. The Naples sera were characterised by low IgA, C3, and C4 levels, increased IgM and IgG concentrations, and high titres of circulating immune complexes. These immunological abnormalities could explain the high concentration of fatal cases.

Acute Disease↗