Factors influencing immediate responses to intradermal allergen administration in patients with respiratory allergy

BACKGROUND: Immediate skin reactions to allergens are influenced by several factors, such as the amount of administered allergen, the level of specific IgE, releasability of mast cells and hyperresponsiveness of the target organ. METHODS: For the evaluation of factors influencing immediate skin response to intradermal allergen administration, we measured the wheal size 15 min after intradermal injection of 0.01-0.02 ml of the following agents: whole-body extract of Dermatophagoides farinae, 1,000 allergy units/ml; histamine, 0.1 mg/ml, and codeine sulfate, 0.09% in saline, and determined total IgE level, specific IgE and IgG subclass antibodies to D. farinae in 53 patients with respiratory allergy. RESULTS: Multiple regression analysis for factors influencing wheal size after intradermal injection of D. farinae, specific IgE antibody level to D. farinae and wheal size after intradermal administration of histamine showed statistically significant results (R2 = 0.42739, p = 0.0000; R2 = 0.50243, p = 0.0185, respectively). Multiple regression analysis for factors influencing wheal size after intradermal administration in the group with high levels of specific IgE to D. farinae (RAST class 3 or more) showed that wheal size after intradermal administration of codeine was the only factor exerting a statistically significant influence (p = 0.0119). CONCLUSION: Based on the above results, we can state that immediate responses to intradermal allergen administration were influenced by the level of specific IgE and hyperresponsiveness of the target organ to histamine, but that the immediate skin allergic responses in the presence of high levels of specific IgE were partially but significantly influenced by the releasability of skin mast cells.     

Cellular inflammatory response to fungal antigen studied with the skin window technique--correlation of the exudate with the evolution of the mycotic infection

The skin window technique, using a coverslip, was applied to study the inflammatory exudate induced by killed pathogenic yeasts in patients with mycotic infections. The presence of eosinophils in the specific exudate after 3 hours seems to indicate specific IgE fixed in the tissues. This was demonstrated by the correlation of this specific eosinophilia with the eosinophilia induced by an anti-IgE serum and with the positive immediate intradermal reactions and by the correlation with serum-specific IgE detected with an immunoenzymatic technique. Increased eosinophilia is related to the active phase of the disease. The eosinophilia in the specific exudate seems to be more reliable than an in vitro technique for the detection of the specific IgE against fungal antigen. In this material, the eosinophilia demonstrated that yeast-specific IgE may be responsible for both immediate and delayed intradermal reactions.     

Comparative study on the assay for IgE antibodies specific for Chamaecyparis obtusa pollen between AlaSTAT and CAP-RAST

Titers of IgE antibody specific for the pollen of Chamaecyparis obtusa (C. obtusa) were determined by AlaSTAT and CAP-RAST in 221 patients with Japanese cedar pollinosis. IgE antibody to C. obtusa tested positive by CAP-RAST at a higher rate (80.5%) than by AlaSTAT (52.6%). The results obtained from the two assays were compared with those from intradermal skin test. CAP-RAST had a higher sensitivity than that of AlaSTAT. Because the two methods showed no differences in the determination of IgE antibody specific for Cryptomeria japonica, the above differences between AlaSTAT and CAP-RAST are surmised to be ascribable to the differences of C. obtusa antigen used in the both assays.     

Predicting unbound phenytoin concentrations in the critically ill neurosurgical patient

BACKGROUND: This study was carried out to compare two techniques used to determine the food specific IgE antibody. METHODS: Thirty-four allergic patients were evaluated for most common food IgE antibodies by multiple allergosorbent chemiluminescent assay (MAST-CLA). IgE antibodies to eight of these food allergens were also measured by Pharmacia CAP (CAP) test. RESULTS: The food specific IgE showed good agreement between MAST-CLA and CAP (kappa = 0.3-0.77). The sensitivity of MAST-CLA assay for food specific IgE antibody was variable comparing with that of CAP system. The accuracy ranged from 0.76 to 0.97. The agreement between the results of MAST-CLA and skin test was variable (kappa = 0.03-0.58). The agreement was poor in wheat, peanut and soybean (kappa = 0.03-0.12). Similar result between CAP and skin test was also obtained (kappa = 0.06-0.82). The agreement was poor in wheat (kappa = 0.06) and milk (kappa = 0.15). CONCLUSIONS: Different results might be related to quality of the extract, how they are performed in vitro test and difference of correspondent allergens employed in the tests.     

Comparative value of skin tests and IgE antibodies in the serum in patients with chronic vasomotor rhinitis

In order to assess values of skin testing and determination of pulp, as a credible indicator considering sensibilisation of an organism, 61 patients suffering from chronic vasomotor rhinitis were tested. By application of "prick" test, skin test results were positive in 30 patients and negative in 31. Presence of specific IgE antibodies in the serum was assessed in all patients by "ELISA" test. In 51 patients (83.6%) both kinds of findings corresponded. In 26 patients both skin parameters were negative while in 10 patients (16.40%) findings did not correspond. It was established that for Dermatophagodies pteronyssinus specific IgE antibodies are determined in serum when pap is 5 mm wide. Grasp pollen always caused strong local reactions, regularly more than 10 mm. Considerably high levels of IgE antibodies was also established while other pollens did not show such correspondence.     

Passive cutaneous anaphylaxis: improvement of quantitative analysis by radioactively labelled antigen

Experiments were performed to improve the quantitative analysis of passive cutaneous anaphylaxis (PCA) by labelling the antigen with radioactive iodine. After intradermal injection of antibodies and intravenous administration of labelled antigen in rats a close correlation was found between the radioactivity measured in skin biopsies and the amount of antigen as well as the amount of antibodies. This direct dependence makes it possible to improve quantitatively the reading of PCA test results. A quantitative correlation was also found when radioactivity is measured over the skin by scanning procedures. Therefore it is not necessary to cut out skin biopsies. Thus the same test animal can be used several times, which minimizes biological variations.     

Anaphylaxis to erythromycin

BACKGROUND: Erythromycin and its salts belong to the larger class of macrolides. Erythromycin is well tolerated. The most common side effects are gastrointestinal distress, nausea, and vomiting, which are dose related. Allergic and pseudoallergic reactions due to macrolide antibiotics are uncommon. Anaphylaxis and acute respiratory distress appear in the literature as case reports. METHODS: We report a 24-year-old man who presented 12 years ago a systemic allergic reaction to penicillin, confirmed by skin tests and detection of specific IgE (RAST). Since then he had tolerated erythromycin on several occasions. Nine months ago, his general practitioner prescribed erythromycin orally as treatment for a respiratory infection. Thirty minutes after taking the first dose, 500 mg, he developed an anaphylactic reaction. The episode subsided with treatment with high dose corticosteroids, antihistamines, and epinephrine. Skin prick tests and intradermal tests were performed with erythromycin at different concentrations. We also measured total IgE and specific IgE to erythromycin by CAP and Phadezym RAST (Pharmacia, Uppsala, Sweden), respectively. We also performed a Prausnitz-Küstner test (PK test), and oral challenge test. RESULTS: Skin testing to erythromycin was not helpful because of cutaneous hyperreactiviness. No significant levels of specific IgE to erythromycin were detected. The oral challenge and the Prausnitz-Küstner test were positive. CONCLUSIONS: The positive history and oral challenge test suggested an anaphylactic reaction to erythromycin. The positive Prausnitz-Küstner test demonstrated the presence of specific IgE to erythromycin.     

Occupational asthma due to latex in health care workers

Immediate hypersensitivity reactions ranging from mild urticaria to life threatening anaphylaxis after exposure to natural rubber latex have been reported frequently in health care workers while occupational asthma due to latex exposure is less well studied. The results of specific challenge tests and immunological tests in four health care workers with work related respiratory and skin disorders induced by the use of latex gloves are described. Occupational asthma was confirmed in three subjects by specific challenge tests. All had a positive skin test reaction to the latex extract; specific IgE antibodies were detected in only one subject. The fourth subject had a negative specific inhalation and skin test reaction to the latex extract. Peak expiratory flow monitoring at work and away from work showed a pattern consistent with work related asthma. These findings confirm that latex is a cause of occupational asthma in health care workers.     

Comparing the enzyme allergosorbens and coated allergen particle tests for latex allergy: which in vitro test should be chosen by an anesthesiologist?

To determine sensitivity and specificity of the enzyme allergosorbens test (EAST) and the coated allergen particle Test (CAP) in detecting specific antibodies against latex, we compared these two methods in a previously investigated sample of an epidemiological study among our anesthesia staff. One hundred one blood samples were tested with EAST and CAP for specific antibodies against latex. Skin test results were used as references. CAP was more sensitive in detecting sensitized individuals than EAST (56% vs 18.8%). Two additional persons with previously negative skin tests were detected. These results suggest that the EAST system is not as sensitive as the CAP system. Therefore, the CAP system should be preferred for the in vitro diagnosis of latex allergy. IMPLICATIONS: Testing for latex allergy requires time-consuming and technically difficult tests. Easy to perform in vitro tests for latex allergy are desirable. Our results indicate that the coated allergen particle test is more sensitive and easy to use than the enzyme allergosorbens test.     

Determination of specific IgE and IgG serum antibodies during immunotherapy in hay fever patients by RAST

A solid phase radio-immunoassay, based on the commercially available antigen preparations on paper discs supplied with the radio-allergosorbent test (Phadebas RAST, Pharmacia) for semi-quantitative determination of specific IgE has been applied to the demonstration of allergen-specific antibodies of the IgG class in sera of hay fever patients. A significant rise of specific IgG antibody has been observed regularly as a result of successful immunotherapy. The rise of such "blocking antibodies" occurred within 3 months after commencement of immunotherapy (IT), well before nasal provocation tests became negative in the patients. No significant decrease of specific IgE antibodies was observed over the one year observation period. While these data confirm earlier results by other groups concerning the appearance of blocking antibodies of IgG class as a result of IT, thus providing additional evidence for its mechanism, they also offer a convenient serological method for monitoring the results of IT.     

Immunologic studies in a case of baker's asthma

A 28-year-old baker with 13 years of occupational experience has developed, over the past several years, sinusitis, rhinitis, contact dermatitis, and asthma. Clinically, all of his symptoms were felt to be related to occupational exposure. Immunologic evaluation consisted of the following tests: intradermal skin testing, leukocyte histamine release, total serum IgE, PK transfer with immunoadsorption, and specific antigen bronchial challenge. Analysis of results would tend to implicate a type I, IgE-mediated immunologic reaction.     

Dynamic change of beta 2-microglobulin in hemodialysis

A candidin, which is a suspension of killed yeast cells, is commonly used for intradermal tests of delayed hypersensitivity, to evaluate the immunological cellular competence of the patient, when the test is applied along with other similar tests. When working with a cellular antigen, the histopathology of positive skin tests reveals a cellular infiltrate which not only presents a characteristic hypersensitivity reaction but also a neutrophilic abscess in the central part. This research presents the results of a comparison between the yeast cell suspension and the polysaccharide antigens, both obtained from the same strains of Candida albicans. The results obtained by skin tests in one hundred individuals were 61.0% with the polysaccharide antigen and 69.0% with the yeast cell suspension antigen. Concordant results concerning the two antigens were observed in 82.0% of the individuals. The discussion section presents an assumption to explain the differences of positivity obtained with the two antigens. We conclude that the polysaccharide antigen can be utilized in the intradermal test of delayed hypersensitivity to Candida albicans.     

Comparison among delayed-type skin tests, serum IgE levels and peripheral blood CD4 in HIV-positive patients

Three groups of HIV-positive men and a control group of healthy subjects were evaluated simultaneously by delayed-type skin tests with recall antigens detection of CD4 cell counts in peripheral blood and the IgE serum levels. Delayed-type skin test reactivity and CD4 cell counts in peripheral blood decreased while IgE serum levels increased as immune imbalance progressed with the worsening of HIV infection (p = 0.003 between controls and HIV-positive patients). The existence of atopy did not significantly influence IgE serum levels in the groups of HIV-positive patients (p < 0.2). Candidin appeared as a useful antigen in the delayed-type skin tests considering that it was the only antigen that remained positive with low values of CD4 cell counts (< or = 250/mm3). The detection of serum IgE levels as well as the performance of delayed-type skin tests with recall antigens are useful tools to evaluate immunological status whereas the number of CD4 in peripheral blood is critical for determining the initiation of antiretroviral therapy.     

Foreign-body granuloma and IgE-pseudolymphoma after multiple bee stings

We report a patient with an unusual combination of an eosinophilic foreign-body granuloma and a pseudolymphoma, with recurrent severe oedema on the forehead, after multiple bee stings. On immunohistology the foreign-body granuloma and lymphoid follicles reacted with monoclonal antibodies against the high- and low-affinity IgE receptors, and against IgE. Prick and intradermal tests with whole-body bee extracts showed positive immediate-type reactions. The eosinophilic granuloma formation and lymphoid follicles may have been induced by a combination of immune complex and cell-mediated hypersensitivity following antigen persistence. Although bee stings are common, as far as we are aware, this complex reaction pattern has not been reported previously.     

The effect of T cell depletion with Campath-1M on immune reconstitution after chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia

Thirty asthmatic children were examined allergic reaction against egg white, gelatin and vaccine solution before and after vaccination using skin prick test. We also measured the levels of specific IgE and IgG antibody against gelatin. The changes in clinical symptoms before and after vaccination were investigated in 25 asthmatic children by evaluating symptom and treatment score. The results were as follows; 1. In one subject who had delayed type of skin reaction to gelatin, the adverse reaction was also recognized at the skin site around 24 hrs after vaccination. In this subject, the levels of serum specific IgE and IgG to gelatin became positive after 5 months. 2. Specific IgE antibodies to gelatin were not detected in all subjects before and after vaccination. 3. The mean values of asthma symptom score before and after vaccination were 3.3 +/- 4.2 and 1.5 +/- 3.3 respectively. Those of treatment score before and after vaccination were 75.6 +/- 35.2 and 76.0 +/- 35.0 respectively. These results suggest that skin testing with gelatin and vaccine solution is useful as a screening method for predicting adverse reactions in asthmatic children and that influenza vaccination can be performed safely in skin test negative children.     

Relationship between antigen and antibody-induced suppression of IgE antibody formation in the rat

Formation of specific IgE antibodies as elicited in Sprague-Dawley rats against Ascaris antigen could be suppressed by intravenous administration both of antigen and of specific antiserum. The suppressive agent in the antiserum was shown to be antibodies of the IgG class, whereas a suppressive effect of cytophilic activity and of IgE antibodies could be outruled. Suppression of IgE response lasted the longer the more antibodies were transferred. An antibody-induced suppression was achieved when antibodies were transferred during an early period (day -3 to day +8), whereas an antigen-induced suppression took place when the antigen was intravenously administered following the antibody-sensitive period (day +8 until day +14). This is consistent with the fact that an antigen-induced suppression of IgE formation requires the presence of a certain amount of antibodies. A strictly peripheric suppression could be outruled, since with elapse of time a decreasing dose of antigen was required to induce a suppression. The results are discussed on the basis of an antigen-antibody complex-induced suppression in the IgE system and its possible central site of action.     

Quantitative differences between the optic nerve head and peripapillary retina in low-tension and high-tension primary open-angle glaucoma

Anti-IgE antibodies directed against the Fc epsilon RI-binding region on IgE inhibit binding of IgE to IgE receptors without inducing mediator release from IgE sensitized cells. In mice these antibodies selectively reduce serum IgE, inhibit antigen induced skin reactions, cytokine production by lung Th2 cells, and pulmonary eosinophil infiltration. Clinical trials in humans reveal that such antibodies are well tolerated and reduce rhinitis symptoms and early and late phase bronchoconstriction responses. Thus interruption of the allergic cascade at the IgE antibody level with non-anaphylactogenic anti-IgE antibodies is effective and represents an attractive intervention for the treatment of allergic diseases.     

Evaluation of risk and diagnostic value of quantitative assays for anti-Toxoplasma gondii immunoglobulin A (IgA), IgE, and IgM and analytical study of specific IgG in immunodeficient patients

To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects, we assayed immunoglobulin A (IgA) and IgE antibodies by means of immunocapture (IC) tests, with revelation done by using a suspension of T. gondii (ICT). We also carried out a simultaneous analytical study of IgG antibodies on cellulose acetate membranes by using the comparative immunological profile method and an enzyme-linked immunofiltration assay (ELIFA). A total of 1,238 samples (serum, cerebrospinal fluid, and aqueous humor from 318 patients) were tested. IgA and IgE antibodies were detected in all heart, kidney, and liver transplant recipients with clinical manifestations of toxoplasmosis; IgA was detected in the aqueous humor of a patient with chorioretinitis. In patients with AIDS-related toxoplasmosis, including the cerebral form, IgA and IgE antibodies or a significant modification of ELIFA IgG values were observed in 38, 19, and 25% of patients, respectively. IgM was detected by ICT only in 12% of patients and aided the diagnosis in 1 of 71 patients. IC tests for specific IgA and IgE alone and combined with ELIFA were positive in 39 and 46% of patients who developed clinical toxoplasmosis, respectively. In a serial study of 16 patients in whom at least one of these three tests was positive, a significant immunological signal sometimes preceded clinical onset by 1, 6, and even 17 months. Similarly, in a group of human immunodeficiency virus-infected patients with evidence of previous exposure to T. gondii but no clinical manifestations, IgA, IgE, and IgA and/or IgE antibodies were detected in only 11, 4, and 12% of patients, respectively. These two situations point to peripheral T. gondii reactivation. IgA and IgE emerged as interesting markers of the risk of toxoplasmosis in immunodepressed patients. They may also provide valuable assistance in the diagnosis of toxoplasmosis, especially because tests for specific IgM are disappointing. However, at least one in two patients with toxoplasmosis showed no detectable immunological reaction, suggesting that this polyisotypic approach should be combined with other noninvasive methods such as gene amplification.     

Definition of a Trichophyton protein associated with delayed hypersensitivity in humans. Evidence for immediate (IgE and IgG4) and delayed hypersensitivity to a single protein

Dermatophytes of the genus Trichophyton cause infections of human skin, nails, and hair. Unlike most Ags, Trichophyton can elicit either immediate (IH) or delayed (DH) hypersensitivity skin reactions. Previous studies isolated a 30-kDa Ag (Tri t 1) that caused IH skin tests. The study presented here used skin testing and in vitro T cell proliferation assays to monitor purification of an Ag, designated Protein IV, associated with DH reactions. Protein IV was purified by cation exchange HPLC; amino acid sequence analysis of the N-terminus and nine internal peptides (143 residues) revealed no homologies to Tri t 1 or to any other known proteins. A mAb-based ELISA was developed to measure Protein IV. Protein IV elicited DH skin reactions in subjects with a history of athlete's foot but also caused IH skin reactions. Serologic responses to Protein IV were studied in 59 adults who had been skin tested with Trichophyton extract. IH skin reactions were associated with a positive RAST (14/23) as well as with specific IgE (13/23) and IgG4 (14/23) Abs to Protein IV. DH skin tests were not associated with IgE or IgG4 Abs. IgE anti-Protein IV Abs were quantitatively correlated with IgG4 Abs (r = 0.57, p < 0.001). Specific IgG Abs to Protein IV were highest in IH subjects (gm = 230 U/ml), and lowest in those with DH (gm = 91 U/ml) or negative (gm = 81 U/ml) skin tests; furthermore, the prevalence of IgG Abs increased significantly with age. Protein IV is the first defined protein associated with both DH and IH skin reactions; these reactions are characterized by distinct serologic responses. The results establish that diverse immune responses in humans can be directed against the same protein.