Topical flunisolide treatment of perennial rhinitis: clinical and immunological effects.

We studied the clinical and immunological effects of three months' treatment with intranasal flunisolide (100 micrograms daily) in 18 allergic patients with perennial rhinitis. 17 were hypersensitive to house dust mite and one to Parietaria pollen only. We found no significant changes in white blood cell count, serum levels of IgE and nasal IgA. However the treatment induced a marked improvement of clinical symptoms in all cases, and we observed a significant reduction of total IgE in nasal secretion. Flunisolide seems to exert this effect through its antiinflammatory action on the nasal mucosa.

Topical flunisolide treatment of perennial rhinitis: clinical and immunological effects.

We studied the clinical and immunological effects of three months' treatment with intranasal flunisolide (100 micrograms daily) in 18 allergic patients with perennial rhinitis. 17 were hypersensitive to house dust mite and one to Parietaria pollen only. We found no significant changes in white blood cell count, serum levels of IgE and nasal IgA. However the treatment induced a marked improvement of clinical symptoms in all cases, and we observed a significant reduction of total IgE in nasal secretion. Flunisolide seems to exert this effect through its antiinflammatory action on the nasal mucosa.

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.

Proviral sequences detection of human immunodeficiency virus in seronegative subjects by polymerase chain reaction.

Human immunodeficiency virus type 1 (HIV-1) can be isolated from lymphocytes and tissues of symptomatic and asymptomatic seropositive subjects. However, in some individuals, virus isolation is not always positive, especially in asymptomatics. In this paper we report the results of HIV-1 DNA detection by means of polymerase chain reaction (PCR), a new technique that permits the amplification of specific DNA sequences. PCR was carried out to amplify two highly conserved env regions on samples from 20 normal individuals used as controls, 20 seropositive patients at different stages of HIV disease and 25 seronegative individuals at high risk for infection, such as sexual partners of seropositive patients and intravenous drug addicts. Eighteen out of 20 seropositive subjects were positive by PCR while among seronegatives HIV DNA was detected in 7/25 individuals. Virus isolation was positive only in 2/7. These subjects, followed for HIV antibody production for a period of 10-12 months, remained seronegative except one case who seroconverted after a few weeks. Long latency of HIV infection without detectable antibodies seems prevalent in these subjects. PCR assay represents a useful technique for identifying proviral sequences in seronegative high-risk individuals, to confirm the infection during its early phases and during the follow-up of patients with HIV disease.

Retinal cotton-wool-like spots: a marker for AIDS?

The prognostic value of ocular manifestations and its correlation with immune changes in HIV-infected subjects was studied longitudinally with an average follow-up of one year (3-22 months). The most common ocular manifestations were retinal cotton-wool-like spots, observed in 58.8% of AIDS patients and in 76.9% of those with ocular involvement. Two of three ARC cases with cotton-wool-like spots developed Pneumocystis carinii pneumonia a few weeks after ophthalmoscopic examination. A close correlation between ocular changes and decrease of CD4+ lymphocytes was observed. In our opinion, these ocular manifestations are as useful as opportunistic infections or AIDS-related neoplasias in the natural history of HIV infection.

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.

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.

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.

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.

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.

Retinal cotton-wool-like spots: a marker for AIDS?

The prognostic value of ocular manifestations and their correlation with immune changes in HIV-infected subjects (75 PGL, 23 ARC, and 17 AIDS) have been longitudinally studied with an average follow-up of one year (3 to 22 months). The most common ocular manifestations were retinal cotton-wool-like spots, observed in 58.8% of AIDS patients and in 76.9% of those with ocular involvement. Two of three ARC patients who showed cotton-wool-like spots developed PCP a few weeks after ophthalmoscopic examination. A close correlation between ocular changes and decrease of CD4+ lymphocytes was observed. In our opinion, these ocular manifestations are as useful an indicator as opportunistic infections or AIDS-related neoplasias in the prognosis of HIV infection.

IgE and IgG4 levels in allergic patients during immunotherapy.

The IgG4 is the predominant antibody response in patients receiving chronic exposure to high doses of antigen, and this seems to be true for immunotherapy as well. The duration and the dose of immunotherapy (IT) seems to increase specific IgG4 levels, but this increase does not seem to be related to the clinical response, seasonal exposure, duration of disease, and IgE antibody levels. The measurement of IgE and IgG4 antibodies to allergens did not predict the clinical effect of immunotherapy in our study. However, it indicated that the patients were continuing to receive the allergenic extracts and that the extract used in vivo, although produced by a different manufacturer, was closely resembling the one used for coating plastic wells in the FAST assay. The increase of antibody titres demonstrate that long term monitoring of IT administration may be accomplished by these in vitro tests, although individual patients may exhibit different responses in time but similar clinical results. Longitudinal studies on a cohort of atopic subjects may help define more precisely doses and timings required to achieve useful indications on both compliance with IT injections and predictivity of its outcome.

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.

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.