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Biomedical subjects

R Paganelli

Publications and source records attributed to R Paganelli.

At least 109 records · Page 6Linked to original sources

Peripheral and intestinal lymphocyte activation after in vitro exposure to cow's milk antigens in normal subjects and in patients with Crohn's disease.

We studied in Crohn's disease and controls the in vitro activation of either peripheral (PBMNC) or intestinal (LPMNC) mononuclear cells in response to the cow's milk antigen beta-lactoglobulin (Blg). The activation of mononuclear cells was investigated by analyzing the kinetics of the transferrin receptor (T9 antigen) and interleukin 2 receptor (Tac antigen) expression. In both controls and Crohn's disease patients Blg (1 microgram/ml) induced a significant (P less than 0.01) increase of T9 and Tac expression by both PBMNC and LPMNC cultured for 3 days. After Blg exposure the counts of T9- and Tac-bearing cells were significantly (P less than 0.05) higher in PBMNC cultures from healthy controls than in those from patients with Crohn's disease. In both groups peripheral T-enriched cell suspensions did not express T9 and Tac when stimulated with Blg but were restored to express either antigen by the addition of 10% autologous adherent cells. In LPMNC cultures from patients with Crohn's disease the Tac expression after 3 days of Blg stimulation was significantly (P less than 0.05) higher than in the autologous PBMNC. Data from this study indicate that in both controls and patients with Crohn's disease lymphocytes sensitized to Blg occur in the circulation as well as in the gut lamina propria. Our data also suggest that in Crohn's disease an increased proportion of lymphocytes sensitized to Blg are recruited from the circulation into the site of the intestinal lesion.

Adult↗

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↗

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↗

Stimulus-related difference in the formation of leukotrienes and PGD2 after immunological and non-immunological challenge of human lung parenchyma "in vitro".

The stimulation of human lung parenchymal fragments with A-23187 induces formation of leukotrienes as well as of PGD2: LTE4 is the compound found in larger amount and independently of the intensity of the stimulus the % of metabolized precursor which is converted to leukotrienes or PGD2 is remarkably similar. However, under conditions of IgE-Anti IgE challenge the predominant conversion of arachidonic acid occurs to PGD2, LTB4 is almost negligible and LTD4 and E4 together represent less than 30% of the oxidative products of arachidonic acid. Whether PGD2 and leukotrienes derive from the same or different subset of cells is unresolved.

Antibodies↗

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↗

[In vitro effects of lysozyme on some specific and non-specific functions of the immune system].

In this paper the in vitro effects of lysozyme on several immunological function was investigated. Henn-egg-white lysozyme (at concentrations ranging between 1 and 10 micrograms/ml) has shown an inhibitory action on mitogen-induced lymphoblastigenesis and autologus mixed lymphocyte reaction. On the other hand, NK activity against K 562 cell line resulted to be increased in the presence of lysozyme. In addition lysozyme has shown to behave as chemokinetic factor increasing PMN random locomotion and inhibiting PMN response only towards complement derived chemotaxins, whereas there was no effect against other chemotactic factors. Then, in addition to its enzymatic activity, a role of lysozyme as modulator of the inflammatory response may be proposed.

Adult↗

Cow's milk hypersensitivity in an elderly woman: clinical and immunologic findings.

We report a case of allergy to cow's milk diagnosed in a 79-year-old woman, who had the habit of drinking large amounts of milk and other dairy products for several years. She had been an asthmatic since the age of 40. At age 65, she noticed a correlation between cheese and milk intake and onset of asthma and two episodes of shock, and she has been avoiding milk for the past 15 years. Positive skin prick tests for cow's milk proteins, grass pollens, and house dust mite were observed. Serum IgE levels were above 3,000 U/mL, with high molecular weight IgE detected by gel chromatography. RAST results confirmed the presence of sensitizations detected by skin prick tests. The patient never suffered from atopic eczema. This unusual case of food allergy with onset after the age of 40 may indicate that prolonged exposure to food antigens in predisposed individuals may lead to the development of allergy even in adult age, lasting for decades after partial elimination of the allergen from the diet.

Aged↗

Isotypic analysis of antibody response to a food antigen in inflammatory bowel disease.

We studied the class-specific antibody response to the cow's milk antigen beta-lactoglobulin (beta-LG) in sera from patients with ulcerative colitis and Crohn's disease. IgG and IgM to beta-LG were significantly higher in patients when compared to healthy non-atopic controls, whereas IgA values were similar, and specific IgE absent in all groups. No correlation between IgG- or IgM-containing immune complexes was found with the corresponding isotype of antibody to beta-LG; however, IgM complexes correlated with serum total IgM in ulcerative colitis. In these patients, IgG antibodies were higher in active cases, whereas IgM increased in patients without signs of disease activity. Antibody titers did not correlate with disease duration or administration of antiinflammatory drugs. This pattern of anti-beta-LG reactivity suggests that the presence of intestinal lesions may be revealed by the selective increase of some antibody isotypes to orally administered antigens. Enhanced mucosal permeability may be studied by this type of serological analysis.

Adrenal Cortex Hormones↗

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↗

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↗

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↗

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↗

Serum IgG, IgA, IgM, IgE, salivary IgA levels and lung function in a healthy male population from the Italian Air Force: a preliminary study.

The reliability of total IgE quantitation in predicting atopic states was evaluated in a highly homogeneous group of 315 male subjects between 19 and 22 years of age, in apparent good health. A parallel evaluation of the other major Ig classes (serum IgG, IgA, IgM and salivary IgA) and a series of lung function tests were also performed. Forty-eight subjects (15%) referred history of allergy (41 respiratory and seven cutaneous). Twenty-one percent of these had IgE greater than 440 IU/ml, a value reported as abnormally high. No significant association was found between atopy and any of the lung function tests performed. Clinical history or IgE levels were not related to other Ig classes. Conversely, serum but not salivary IgA levels were significantly reduced in tonsillectomized subjects. From the present data it appears that neither IgE determinations nor performing lung function tests can be considered reliable substitutes for an accurate history and evaluation of clinical parameters.

Adolescent↗