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Biomedical subjects

F Aiuti

Publications and source records attributed to F Aiuti.

At least 181 records · Page 10Linked to original sources
PubMed1984

Classification of patients with T-cell chronic lymphocytic leukemia and expansions of granular lymphocytes: heterogeneity of Italian cases by a multiparameter analysis.

The peripheral blood mononuclear cells (PBMC) from 750 Italian patients with chronic lymphocytic leukemia (CLL) were evaluated in order to detect cases with T-cell expansions. The PBMC of 18 patients (2.4%) were found to be capable of rosetting with sheep red blood cells. Further characterization of these cells with a panel of monoclonal antibodies and other immunological and cytochemical tests led us to tentatively subdivide these 18 patients into three groups. The first one included 6 patients whose cells expressed a T-helper phenotype: they exhibited frequent skin involvement and an aggressive clinical course, and some of the patients in this group demonstrated chromosome abnormalities. On the other hand, group 2 (10 cases with expansions of granular lymphocytes and/or T suppressor-bearing phenotype cells) usually presented with a mild clinical course. These cases did not generally require therapy and a diagnosis of leukemia could not be unequivocally confirmed. Cells from the two remaining patients displayed both B-cell markers and E-rosetting ability, thus belonging to the rare group of false T-cell CLL. In fact, the clinical course and management of the latter cases were similar to those of classical B-CLL disease. In the first and second groups, mechanisms reported to be involved in mature T-cell proliferations (response to interleukin-2, production of interleukin-2 or interferon) were investigated, but the cells under study displayed neither growth ability nor lymphokine production in the above assays. In addition, these cells were negative with the anti-Tac monoclonal antibody that appears to recognize the receptor for interleukin-2. More importantly, none of these patients had serum antibodies to the recently described human T-cell leukemia/lymphoma virus (HTLV), possibly responsible for Japanese and West Indian adult T-cell leukemia (ATL) and for sporadic cases of ATL observed in other countries. Taken together, our results outline some differences between European and ATL patients. Furthermore, the data presented point out the heterogeneity of the disease and emphasize that an immunological classification and, in particular, the detection of a helper phenotype have relevant prognostic and therapeutical importance.

Adult↗
PubMed1984

Interferon production in primary immunodeficiencies.

Alpha- and gamma-interferon (IFN) production by peripheral blood mononuclear cells (PBMC) from 18 patients affected by primary immunodeficiency syndromes was examined and compared with that of 20 normal donors. Patients included 8 with common variable immunodeficiency (CVI), 2 with congenital agammaglobulinemia, 4 with ataxia-telangiectasia, 2 with hyper-IgE syndrome, 1 with chronic EBV infection, 1 with combined immunodeficiency, and 1 with immunodeficiency with hyper-IgM. No spontaneous IFN production was observed in either patients and controls. Newcastle disease virus-induced alpha-IFN production was found to be normal in all patients. Gamma-IFN was induced by both galactose oxidase and staphylococcal enterotoxin (B). Gamma-interferon production was low or undetectable in patients with ataxia-telangiectasia, in immunodeficiency with hyper-IgM, and in hyper-IgE syndrome. No major defect of gamma-IFN was found in other types of immunodeficiency, despite the presence of occasional low producers (1 of 8 CVI patients and 1 case of congenital agammaglobulinemia). No correlation was found between IFN production and natural killer activity in individual patients. The analysis of lymphocyte subsets by monoclonal antibodies revealed gross imbalances of helper/inducer and suppressor/cytotoxic subpopulations, but no overall correlation could be established with gamma-IFN production. The observation of major defects in gamma-IFN yield only in diseases with depression of T cell-mediated immunity might contribute to a better understanding of the pathogenetical mechanisms in these diseases. Moreover, future studies should monitor these in vitro functions and their modifications by in vitro or in vivo manipulations.

Adolescent↗
PubMed1984

A placebo-controlled trial of thymic hormone treatment of recurrent herpes simplex labialis infection in immunodeficient host: results after a 1-year follow-up.

Twenty-one immunodeficient patients with recurrent herpes simplex labialis (HSL) were randomly allocated to either the saline or the bovine thymus extract Thymostimulin (TS) group and treated for a period of 6 months. A total of 17 recurrences with a mean severity index of 266.2 +/- 192 in the TS-treated group versus a total of 62 recurrences in the placebo group (score 458.8 +/- 299.6) were observed after 12 months of follow-up. A significant increase of total WBC (P less than 0.05 versus control group), lymphocyte count, and T-cell number (P less than 0.001) were detected in the TS group after 6 months as well as after 12 months. In vitro lymphoproliferative responses to herpes simplex virus antigen and natural killer cell activity were also significantly higher (P less than 0.05) in the TS group, whereas no significant difference in antibody titers to herpes simplex could be detected between the two groups. TS may be potentially useful in preventing viral reactivation in immunocompromised hosts by potentiating cell-mediated immune responses. Further studies evaluating TS for prophylaxis of infection in patients at risk should be considered.

Adolescent↗
PubMed1984

Comparison of pathologic and normal sera by immune complex determination: five disease groups within 190 samples are discriminated by computer-selected combinations of 13 methods. Report of the Italian committee for the study of immune complexes (WIC).

Pathological (190) and normal (33) sera were tested for their content of circulating immune complexes (CIC) by a battery of 13 assays performed in 11 laboratories. Statistical processing was done both by pooling all pathological samples and by extracting those falling into well-defined disease groups, i.e., rheumatoid arthritis, diabetes, lupus, melanoma, and glomerulonephritis. Highly significant correlations between methods--taken two at a time--for each disease differed in proportion (ranging from 6 to 30%) and in the pattern displayed on a checkerboard. Disease-linked patterns were also found when a function maximizing discrimination between pathological and normal samples was derived by combining the information from all methods. Here the order and the weight attributed by the computer to the methods differed for each of the disease groups. Taken together these results are interpreted as an indication that all assays may not determine the same classes of CIC, and thus vary in sensitivity depending on the prevailing properties of the complexes present in the serum, which in turn may depend on the etiology, pathogenesis, and stage of the disease.

Antigen-Antibody Complex↗
PubMed1984

Defective interferon-gamma production in ataxia-telangiectasia.

The in vitro production of interferon-alpha and -gamma (IFN) by peripheral blood mononuclear cells from four patients with ataxia-telangiectasia was compared to that of healthy controls. Normal values of IFN-alpha were obtained in all cases. However, patients with ataxia-telangiectasia showed a great reduction or absence of IFN-gamma production after induction with either staphylococcal enterotoxin B or galactose oxidase. This defect was accompanied by the absence of secretion of another lymphokine, namely, interleukin 2 (IL-2), in one case. Lymphoproliferative response to phytohemagglutinin (PHA) was severely depressed in all patients. Near normal values of T lymphocytes were found, but the ratio of OKT4+/OKT8+ subsets was reduced in most patients, due to a decrease of OKT4+ lymphocytes. Deficiency of IFN-gamma may contribute to the abnormalities of immune functions and immunoregulation observed in ataxia-telangiectasia, and it may represent an additional cause of the high incidence of viral infections and neoplasia in this disease.

Adolescent↗
PubMed1984

Bone marrow transplantation and thymopoietin pentapeptide treatment in two infants with immunodeficiency with predominant T-cell defects.

Two infants with immunodeficiency with predominant T-cell defects received transplants of HLA-identical bone marrow cells along with thymopoietin pentapeptide (TP-5) treatment and no prior immunosuppressive therapy. Both patients achieved durable engraftment with early reconstitution of cell-mediated immunity. The study of cell surface antigens with monoclonal antibodies (MoAb) revealed that the early appearance of T-cell subsets defined by OKT4 and OKT8 MoAb occurred. Neither of the patients showed any signs or symptoms of graft versus host disease over a 1-year period. This experience suggests that patients with T-cell deficiency who do not benefit from thymic hormones alone can be successfully treated by bone marrow transplantation. The association of TP-5 with bone marrow transplantation seems to induce an early and stable reconstitution and to protect against fatal post-transplant infection.

Antibodies, Monoclonal↗
PubMed1984

A preliminary report on the immunological responses after oral vaccine (Ty 21a).

Humoral and cell-mediated immune responses, specific for lipopolysaccharide (LPS), were evaluated before and after oral immunization with the Ty 21a strain of Salmonella typhi in a group of healthy volunteers. No rise in seric and foecal antibody titres, detected by the ELISA technique, was seen after vaccination. On the contrary, we were able to demonstrate the development of specific cell-mediated immunity, as assayed by the leukocyte migration inhibition test, 21 days after vaccination. This conversion was still present 40 days after the last dose of vaccine. We believe that the Ty 21a strain of S. typhi, recently proposed for immunization against typhoid fever and based on the use of live micro-organisms, is effective due to its ability to induce specific cell-mediated immunity.

Administration, Oral↗
PubMed1983

Thymopoietin pentapeptide treatment of primary immunodeficiencies.

26 patients with primary immunodeficiencies (3 infants with severe combined immunodeficiency [SCID] 3 with DiGeorge syndrome, 6 with T-cell defect or SCID with B cells, 4 with common variable hypogammaglobulinaemia and associated T-cell defect, 5 with ataxia-telangiectasia, and 5 with hyper-IgE syndrome) were treated with thymopoietin pentapeptide (TP-5) at a dose of 0 . 5 mg/kg daily for 2 weeks and then 3 times a week at 0 . 5 mg/kg for 10 weeks, 3 patients with DiGeorge syndrome and 3 with primary T-cell defect demonstrated pronounced clinical and immunological improvement during treatment. None of the patients with SCID and 3 of 6 patients with SCID with B cells or primary T-cell defect showed any clinical or immunological changes during therapy. In 5 patients with ataxia-telangiectasia clinical manifestations and immunological tests were unchanged by TP-5. Abnormality of T cells in cases of hyper-IgE syndrome was not corrected by TP-5 treatment.

Adolescent↗
PubMed1983

Heterogeneity of immunological abnormalities in ataxia-telangiectasia.

Peripheral blood mononuclear cells from five patients with ataxia-telangiectasia were evaluated for their reactivity with a panel of monoclonal antibodies directed against T-cell subsets and for their in vitro functions in a pokeweed mitogen-induced immunoglobulin biosynthesis assay. All the patients had significantly reduced proportions of cells identified by monoclonal antibodies to subpopulations of T lymphocytes with helper activity (OKT4 and 5/9) and produced low amounts or no IgA and IgG in vitro. Immunoglobulin biosynthesis was increased by the addition of normal x-irradiated peripheral blood mononuclear cells in one of three patients, suggesting a helper T-cell deficiency in this patient and intrinsic B-cell defects in the other two. Two patients had increased proportions of cells identified by a monoclonal antibody to a subpopulation of T lymphocytes which includes suppressor T cells (OKT8), and their cells were able to suppress immunoglobulin biosynthesis by peripheral blood mononuclear cells from normal donors. These findings indicate heterogeneous disturbances of immunoregulatory mechanisms in ataxia-telangiectasia.

Adolescent↗
PubMed1983

Primary immunodeficiency syndromes in Italy: a report of the national register in children and adults.

The Italian Register for Immune Deficiencies was organized in 1977. Seven hundred ninety-seven cases of primary immunodeficiencies, diagnosed according to the World Health Organization criteria, have been registered up to April 1982. In this paper we report the percentages of the different forms of primary immunodeficiencies and the incidence of neoplastic and autoimmune diseases. A prevalence of humoral defects and selective IgA deficiency was found, followed by T-cell disorders. Two and thirty-eight hundredths percent of the patients developed cancer, and 5.89% developed autoimmune diseases. A comparison among the Italian, Swedish, and Japanese Registers showed a higher incidence of IgA defects in the Italian Register while nonspecific phagocyte defects were more frequent in the Swedish Register. The incidence of cancer and autoimmune disorders is similar to that observed in other registers.

Adult↗
PubMed1983

Severe combined immunodeficiencies, primary T-cell defects and DiGeorge syndrome in humans: characterization by monoclonal antibodies and natural killer cell activity.

Peripheral blood mononuclear cells from three patients with severe combined immunodeficiency (SCID), three with SCID whether B cell positive or with pure T-cell defect, and two with DiGeorge syndrome were analyzed with a panel of monoclonal antibodies against immature and mature T-cell subsets. Natural killer (NK) cells were enumerated by the use of the HNK-1 monoclonal antibody. NK activity against the K562 and MOLT 4 cell lines was also investigated. According to the monoclonal antibodies profile and the NK activity, patients could be divided into three groups. Patients with classical SCID had no detectable circulating T cells as well as NK cells and activity, probably due to an early block in stem cell differentiation. Patients affected by SCID with B cells or pure T cell defect showed a decrease in lymphocytes with mature phenotypes but prothymocytes or immature thymocytes circulated in peripheral blood. Children with DiGeorge syndrome had a decrease in mature thymocytes and, in this study, NK cells were normal. These data help to clarify both the preeminent immunologic features of SCID and related syndromes and the character of NK cells.

Adolescent↗
PubMed1983

Levamisole therapy: clinical and immunological evaluation in herpetic keratitis.

Thirty patients with herpetic keratitis, recurrent in 17, were examined and submitted to an immunological evaluation for cell-mediated immunity (E rosette forming cells, absolute number of T lymphocytes, skin tests). A group of 15 patients was treated with Levamisole (2.5 mg/kg body weight, 3 days a week), while the control group received no Levamisole. The observation period varied from 6 to 24 months. The clinical follow-up showed a reduction in the severity and duration of herpetic attacks and in the frequency of relapses compared with the control group. The immunological findings indicated a normalization of E rosettes in all the patients (treated and controls).

Adolescent↗
PubMed1983

In vitro and in vivo effect of sisomicin and gentamycin on polymorphonuclear chemotaxis and phagocytosis.

Ten patients with acute bacterial infections were studied to demonstrate the influence of two aminoglycosides, sisomicin and gentamycin on polymorphonuclear (PMN) chemotactic and phagocytic functions. Five of these subjects were treated with gentamycin and five with sisomicin both at a dosage of 2.5 mg kg-1 day-1. The assays were performed before and after 5 days of therapy. Before beginning treatment, the in vitro action of the aminoglycoside antibiotics (20 micrograms ml-1) was also tested. Granulocytes from 8 healthy people were used as controls. After therapy, no significant difference in basic values was found in either the gentamycin treated or in the sisomicin treated group. Similar results were obtained in incubation tests on both patients and healthy subjects. In conclusion, we conclude that the use of these mentioned aminoglycoside antibiotics, at the therapeutical doses employed, does not interfere with the PMN functions.

Adult↗
PubMed1983

Detection and partial characterization of circulating immune complexes in hydatid disease.

Thirty sera from eight patients with disseminated or localized hydatid disease have been examined for the presence of circulating immune complexes (CICs) by the conglutinin-binding assay and for immunoglobulin levels. The highest levels of CICs were of the immunoglobulin A (IgA) class, with lower values of IgG-CIC and IgM-CIC; these results did not correlate, except for IgG, with the free immunoglobulin levels. Efforts to identify parasitic antigen(s) involved in the CIC formation with different methods have been unsuccessful. In the follow-up of each patient, CIC appeared to be better correlated to clinical conditions than to hemagglutination titers. We have concluded that the presence of CIC in hydatid disease is probably an expression of B-cell polyclonal activation and that these complexes are valuable in the clinical monitoring of the disease.

Antigen-Antibody Complex↗
PubMed1983

In vitro enhancement of bone marrow natural killer cells after incubation with thymopoietin32-36 (TP-5).

Natural killer (NK) activity and interferon (IFN) production of spleen and bone-marrow lymphocytes were investigated in 8 to 10-wk-old C3HeB/FeJ/Cne mice, before and after in vitro exposure to the synthetic pentapeptide corresponding to positions 32-36 of the sequence of thymopoietin (TP-5). NK activity was studied against the 51Cr-radiolabelled Moloney virus-induced lymphoid cell line YAC 1, while IFN titres were determined by the inhibition of cytopathology of vesicular stomatitis virus on L929 cells, scored for CPE after 24 h from viral infection. A part of the lymphocytes from the spleen and bone marrow were incubated with different preselected doses (0.1, 1 and 10 micrograms/ml) of TP-5 for 1 h at 37 degrees C, and a part were left unincubated. At the end of the incubation time they were tested, without being washed, for NK activity and IFN production. TP-5 was able to significantly enhance (P less than 0.001 chi 2 test with Yate's correction) bone-marrow NK activity at a dose of 1 microgram/ml, while it was ineffective on spleen cells. A decrease of NK activity, seemingly due to a toxic effect, was observed both in bone-marrow and spleen lymphocytes, after incubation with a dose of 10 micrograms/ml. IFN production was not enhanced after exposure to TP-5. In all, our experiments suggest that TP-5 may enhance bone-marrow NK cells, perhaps by permitting the maturation of their precursors, as already known for T-cell-mediated cytotoxicity. Its effect is independent on IFN production and might be able to induce the rearrangement of certain surface specific receptors.

Animals↗
PubMed1983

Defect of T helper lymphocytes, as identified by the 5/9 monoclonal antibody, in patients with common variable hypogammaglobulinaemia.

Peripheral blood lymphocytes from 17 patients with common variable hypogammaglobulinaemia (CVH) were tested for reactivity with the 5/9 monoclonal antibody which reacts with about 15% of normal T-PBL in which all helper activity is found. In PBL from CVH patients, the proportions of OKT4 and OKT8 positive cells were also determined. Five patients had normal percentages of 5/9 cells and a normal OKT4/OKT8 ratio. Twelve patients had significantly decreased (or absent) 5/9 lymphocytes. Among these, five had decreased 5/9 cells and a normal OKT4/OKT8 ratio and seven had decreased 5/9 cells and an inversion of the OKT4/OKT8 ratio. The deficiency of the helper phenotype T cell subpopulation identified by the 5/9 monoclonal antibody in many patients with CVH may be relevant in the pathogenesis of this disease.

Adolescent↗