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Biomedical subjects

R Paganelli

Publications and source records attributed to R Paganelli.

At least 91 records · Page 5Linked to original sources

Intestinal permeability in patients with chronic urticaria-angioedema with and without arthralgia.

We evaluated the clinical response to oligoallergenic dietary treatment and the intestinal absorption of a protein antigen, cow milk beta-lactoglobulin (BLG) in 24 patients with chronic urticaria/angioedema syndrome 13 of whom also suffered from joint symptoms. Sixteen patients (77% of those with arthralgia) responded to diet (RD) with marked reduction of symptoms; the others did not respond (NR). Ten (all but one RD with arthralgia) had increased permeability to BLG after oral administration of cow milk. Four with high titers of IgG to BLG showed the highest absorption of BLG and the groups with arthralgia showed higher BLG levels than those without arthralgia. In all cases, specific IgE to cow milk was absent. These data suggest that the symptoms of a subgroup of patients with chronic urticaria, and especially patients with joint complaints that subside with diet, are related to excess intestinal permeability. The measurement of gut permeability to food proteins may be useful to define those who may benefit from dietary restriction.

Adolescent↗

Relative increase of T cells expressing the gamma/delta rather than the alpha/beta receptor in ataxia-telangiectasia.

In ataxia-telangiectasia, B-cell and T-cell deficiencies are thought to be due to a defect of rearrangements of immunoglobulin and T-cell receptor genes. T cells recognize antigens through two types of CD3-associated receptors: alpha/beta chains on mature cells and gamma/delta chains mostly on immature cells. We studied 10 patients with ataxia-telangiectasia and found that most had a relative increase of circulating T cells bearing gamma/delta receptors rather than alpha/beta receptors, as compared with normal subjects (P less than 0.001). Patients with other immune deficits, including eight with common variable immunodeficiency, one with Wiskott-Aldrich syndrome, two with hyperimmunoglobulinemia E syndrome, and one with severe combined immunodeficiency, had normal ratios of gamma/delta-bearing to alpha/beta-bearing cells. A marked predominance of gamma/delta-bearing T cells was found in a patient with a primary T-cell defect. The relative increase in gamma/delta-bearing T cells in the patients with ataxia-telangiectasia was largely accounted for by cells that reacted with the monoclonal antibody BB3, an apparently distinct subset of T cells that selectively express the C gamma 1 gene product of the T-cell receptor. Although they had normal ratios of gamma/delta-bearing to alpha/beta-bearing T cells, the patients with common variable immunodeficiency had a significant increase (P = 0.01) in the number of T cells expressing C gamma 2 that reacted with the monoclonal antibody delta-TCS-1. We conclude that the increased ratio of gamma/delta-bearing to alpha/beta-bearing T cells in ataxia-telangiectasia may reflect both a recombinational defect that interferes with T-cell and B-cell gene rearrangements and an inability to repair damage to the DNA.

Adolescent↗

Prevalence of gallstones in patients with primary immunoglobulin deficiency. Evidence for lack of association.

In the early 1970s an increased prevalence of gallstones was reported in adults and children with immunoglobulin deficiency. As the advent of ultrasonography has largely changed the diagnostic approach to gallstones, we have reevaluated the prevalence of cholelithiasis in a group including 37 patients with common variable immunodeficiency and seven patients with other forms of primary immunodeficiency. All patients were receiving intravenous gammaglobulin replacement since 1983 or, in more recent cases, soon after the diagnosis was made, and therefore had relatively few infections. All patients underwent a hepatobiliary ultrasonogram and blood sampling. Data were compared, after age and sex standardization, with those obtained by the GREPCO in a free-living population of 1239 men and 1081 women. Only two women with immunoglobulin deficiency had gallstones. One of these was obese and had had one pregnancy. Both were asymptomatic. None of the patients studied had a history of cholecystectomy or evidence of biliary sludge. Thus, the observed prevalence rates of gallstone disease were 8.7% in women and 0% in males, respectively, against expected values of 9.5% and 3.2%. Immunodeficient patients expressed several putative risk factors for gallstones in the low range (body mass index, total and HDL cholesterol, and blood glucose in both sexes, and triglycerides in men). We conclude that gallstone disease is not more frequent in patients with immunodeficiency syndromes undergoing immunoglobulin therapy than in the general population.

Adult↗

Intestinal permeability in irritable bowel syndrome. Effect of diet and sodium cromoglycate administration.

We studied 14 patients with irritable bowel syndrome for the presence of increased intestinal permeability to food antigens and their responses to diet with and without disodium cromoglycate. After a standardized oral challenge with cow milk, serum beta-lactoglobulin was increased above control values in three patients. This finding did not correlate with response to hypoallergenic diet or treatment with disodium cromoglycate for 3 weeks. However over 50% of patients improved after diet with and without DSCG (2/5 on diet only and 5/7 with disodium cromoglycate of 12 evaluable cases). Since only two patients had elevated serum IgE levels, our results suggest that intolerance rather than hypersensitivity to foods may play a role in the disease. The tests we used to identify immunologic mechanisms could not predict which patients would do better on the diet and/or the drug.

Adolescent↗

Extremely low frequency pulsed electromagnetic fields increase interleukin-2 (IL-2) utilization and IL-2 receptor expression in mitogen-stimulated human lymphocytes from old subjects.

The effects of the exposure of mitogen-stimulated human lymphocytes from aged subjects to low-frequency pulsed electromagnetic fields (PEMFs) were studied by measuring the production of interleukin-2 (IL-2) and the expression of IL-2 receptor. PEMF-exposed cultures that presented increased [3H]thymidine incorporation showed lower amounts of IL-2 in their supernatants, but higher percentages of IL-2 receptor-positive cells and of T-activated lymphocytes. Taken together, these data suggest that PEMFs were able to modulate mitogen-induced lymphocyte proliferation by provoking an increase in utilization of IL-2, most likely acting on the expression of its receptor on the plasma membrane.

Aged↗

IgG anti-IgE from atopic dermatitis induces mediator release from basophils and mast cells.

IgG antibodies containing anti-IgE activity isolated from a patient with atopic dermatitis (H-aIgE) induced mediator release from human basophils and mast cells isolated from skin and lung tissues. The release of histamine was calcium- and temperature-dependent and did not involve cytotoxicity. There was an excellent correlation (r = 0.88; p less than 0.001) between the maximum percent histamine release from human basophils induced by rabbit anti-IgE (R-aIgE) and H-aIgE. H-aIgE was approximately 30 times more potent than R-aIgE in inducing mediator release from human basophils, skin, and lung mast cells. H-aIgE specifically desensitized human basophils to a subsequent challenge with both H-aIgE and R-aIgE. Lactic acid removal of IgE from human basophils blocked the releasing activity of both R-aIgE and H-aIgE. Passive sensitization with hyperimmune sera or purified IgE myeloma restored the response of basophils to both R-aIgE and H-aIgE. IgE purified from three different myeloma patients concentration-dependently blocked the histamine releasing activity of both R-aIgE and H-aIgE.

Adolescent↗

Intestinal permeability and antigen absorption in rheumatoid arthritis. Effects of acetylsalicylic acid and sodium chromoglycate.

Intestinal permeability was measured using cow's milk beta-lactoglobulin absorption (BLG) as a permeability marker in 14 patients with active and inactive rheumatoid arthritis (RA) under three different conditions: after a washout period, after treatment with acetylsalicylic acid (ASA) associated with disodium chromoglycate (DSCG), and with ASA only. No intolerance to cow's milk was present and serum IgE levels were in the normal range in 12 of 14 patients. IgG anti-IgE were present in 7 of 13 patients tested. When off treatment the intestinal permeability to BLG in RA patients was not increased as compared to controls, but we found a significative difference between active and inactive RA. ASA administration strongly increased BLG absorption, not prevented by DSCG pretreatment. In normal controls treated with a single dose of ASA we obtained similar results. Our results suggest that prolonged treatment with nonsteroidal anti-inflammatory drugs induces an increase of food antigen absorption, apparently not related to anaphylaxis mediator release, with possible clinical effects.

Adult↗

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↗

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↗

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↗

IgG subclasses to food antigens.

Involvement of sub-classes of IgG that are specific for food allergens in anaphylactoid reactions and some manifestations of atopy no longer needs to be shown. Accordingly, sub-classes of IgG specific for ovalbumin (OVA) and beta-lactoglobulin (BLG) were compared in healthy subjects and those who presented with an intolerance or food allergy to OVA and BLG to decide whether a restrictive diet was necessary. The four sub-classes of IgG1, IgG2, IgG3 and IgG4 were isolated in all the groups. IgG4 was highest in the allergic subjects and the IgG sub-class values were modified by the diet differently in each group. Unfortunately, the small number of subjects does not allow the formation of a definite conclusion to this study.

Antigens↗

Clinical and immunological findings in four infants with Omenn's syndrome: a form of severe combined immunodeficiency with phenotypically normal T cells, elevated IgE, and eosinophilia.

We report four cases of Omenn's syndrome (OS), an autosomal recessive disease characterized by early erythrodermia, protracted diarrhea, severe infections, lymphadenopathy, hepatosplenomegaly, failure to thrive, and leukocytosis with marked eosinophilia. The immunological investigations revealed B lymphopenia with increased levels of serum IgE and marked depression of T-cell activation, not restored by the addition of exogenous interleukin 2 (IL-2). IL-2 and interferon-gamma (IFN-gamma) production in vitro were very low or absent. One patient was treated with HLA-identical bone marrow transplant with a complete remission of the clinical picture and the immunological defect. The infant died of graft versus host disease 4 months after the graft. For the remaining three infants the outcome was also fatal within the first year of life. In conclusion, OS should be considered a severe combined immunodeficiency disease with peculiar clinical, immunological, and histological findings.

Antibody Formation↗