Allergen-specific IgE and IgGd antibodies in atopic and normal dogs

Intradermal skin tests (IDSTs) were performed on 65 atopic and 24 normal dogs. The levels of allergen-specific IgE and IgGd antibodies were determined in serum samples by enzyme-linked immunosorbent assay (ELISA) using the same 12 allergens that were used in the IDST on normal dogs. The correlation between the levels of IgE and IgGd to Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP) was examined. The sensitivity, specificity and positive and negative predictive values of allergen-specific IgE and IgGd levels in the total dog population were also compared. Results were consistent and reproducible for 9/12 allergens, but in the case of house dust, flea and Alternaria tenuis, a less discriminating standard curve and the fact that the negative control gave positive results, suggests non-specific binding and that these allergens are complex and should not be employed without further purification. A high percentage of atopic dogs had positive IDSTs and detectable IgE and IgGd antibodies to DF, DP and house dust. Similar results were obtained in the normal dog population. There were significant correlations between allergen-specific IgE and IgGd levels to DF and DP. However, in contrast to IgE, allergen-specific IgGd in normal dogs was higher than in atopic dogs. Furthermore, a high percentage of the atopic population had detectable IgGd to unrelated allergens, despite negative IDSTs. Overall, the negative predictive values were similar for both IgE and IgGd. Sensitivities were higher in the allergen-specific IgGd assays, but the specificities and positive predictive values were higher in the allergen-specific IgE assays. In conclusion, the concordance of IDSTs with ELISA results to DF and DP in normal dogs without clinical signs implied the possible heterogeneity of IgE in dogs. The presence of IgGd directed against apparently irrelevant allergens in atopic patients and the high levels of IgGd in normal dogs to the most common allergens, DF and DP, implied an uncertain role of IgGd in canine atopic disease. Therefore, the detection of allergen-specific IgE is a more useful adjunct to the diagnosis of atopic disease in the dog than IgGd.     

Allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis

The majority of allergen-specific T cells derived from inhalant allergen patch test lesions in patients with atopic dermatitis were previously found to produce a restricted type-2 cytokine pattern. Recent studies, however, have revealed that in chronic eczematous skin lesions of patients with atopic dermatitis, expression of the type-1 cytokine interferon-gamma predominates. To evaluate cytokine production by allergen-specific T cells in chronic atopic dermatitis, we established house dust mite (Dermatophagoides pteronyssinus)-specific T-cell clones from the dermis of chronic skin lesions of sensitized adult patients with atopic dermatitis. Frequencies of skin-derived T cells proliferating in the presence of Dermatophagoides pteronyssinus were between one in 138 and one in 4255, indicating that only a minority of skin-infiltrating T cells are allergen specific. When these cells were analyzed for their capacity to produce interferon-gamma, the majority (71%) of these cells were found to express interferon-gamma mRNA and to secrete interferon-gamma protein, either alone or in combination with interleukin-4. Phenotypic analysis revealed that 15% of skin-infiltrating allergen-specific T cells were CD8+. No selection of Vbeta elements was detected in Dermatophagoides pteronyssinus-specific T-cell clones. These studies demonstrate that allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in lesional atopic dermatitis. The notion that the majority of allergen-specific, skin-infiltrating T cells are capable of producing interferon-gamma further supports the concept that interferon-gamma expression has major pathogenetic relevance for the chronic phase of atopic dermatitis.     

Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion

A new immunoassay system utilizing new automatic instrumentation, new software for evaluation of data, and reagents updated for increased speed and accuracy was evaluated. Six clinical studies included 894 consecutive patients. Major symptoms were rhinoconjunctivitis, asthma, atopic dermatitis, and urticaria. The prevalence of inhalant allergy was 54-69%. Phadiatop, detecting atopic sensitization to common inhalant allergens, agreed with clinical diagnosis in 764/836 cases (91.4%). The clinical sensitivity and specificity were 93% and 89%, respectively. The clinical sensitivity and specificity of UniCAP specific IgE derived from 5170 comparisons with clinical diagnosis were 89% and 91%, respectively. Specific IgE measurements in UniCAP and in the Pharmacia CAP System agreed in 266/274 cases (97%). A comparison of the sensitivity and specificity of Pharmacia CAP System RAST in 1987 and with UniCAP specific IgE in 1995 showed equivalent performance without change of efficacy or degradation of IgE antibodies after 8 years. The systems were equivalent also in terms of measured values (r=0.96, slope=1.12), confirming the standardization of allergens and of assay calibration. UniCAP is an efficient laboratory system for routine diagnostic testing of allergy and a valuable tool for basic studies on allergens and antibodies.     

Monitoring of serologic immune parameters in inflammatory skin diseases

This paper deals with the correlation of clinical scoring and serologic markers of inflammation in atopic dermatitis and psoriasis. Serum eosinophil cationic protein (ECP), soluble interleukin-2 receptor (sIL-2R), total serum IgE, IgG and IgM anti-IgE antibodies, and IgE immune complexes were evaluated in monitoring inflammatory skin diseases such as atopic dermatitis and psoriasis. Well-established clinical activity scores were used as standards in recording skin improvement under treatment in a clinical setting. Serum ECP was found to be increased in both atopic dermatitis and psoriasis patients compared to normal controls; sIL-2R and IgE immune complexes were increased only in atopics with increased serum IgE. Anti-IgE antibodies did not show any deviation in both groups of patients. There was a significant elevation of sIL-2R and IgE immune complexes and a nonsignificant elevation of ECP in high-IgE atopics in comparison to those with normal serum IgE. In both groups of patients, there was a significant reduction of ECP and sIL-2R accompanying the improving skin condition. Serum IgE and the other immune parameters failed to respond. In contrast to other studies, serum ECP failed to correspond significantly with disease activity in our study. Our results showed measurable changes of ECP and sIL-2R for atopic dermatitis and/or psoriasis under treatment, but comparison to clinical scores remains difficult due to the different basis of the two systems. The only significant correlation was established for relative changes in sIL-2R and psoriasis area and intensity (PASI), a correlation which might be a useful approach in psoriasis.     

Reversal of human allergic T helper 2 responses by engagement of signaling lymphocytic activation molecule

Allergen-specific Th2 cells accumulate at high frequencies in the skin of patients with atopic dermatitis (AD), where they contribute to the induction and maintenance of the lesions that are characteristic for the disease. Attenuation of these lesions in response to successful therapy is associated with a reduction in IL-4-producing Th2 cells and the appearance of IFN-gamma-producing Th cells. In this study, we demonstrate that engagement of the signaling lymphocytic activation molecule (SLAM) by an agonistic mAb, during allergen-specific expansion of highly polarized Th2 cell populations derived from skin biopsies of AD patients, results in the generation of stable populations of IFN-gamma-producing cells. SLAM-mediated reversal of Th cell phenotype has important biologic consequences, because supernatants of these activated, allergen-specific Th cells fail to induce IgE synthesis by purified B cells costimulated by anti-CD40 mAbs. Thus, highly polarized, allergen-specific Th2 cell populations derived from the skin of AD patients can be reversed into Th cell populations that contain IFN-gamma-producing cells and that do not support IgE synthesis. These results define a new mechanism to promote Th0/Th1 differentiation and suggest a potential role for anti-SLAM mAbs in the treatment of Th2-mediated allergic diseases.     

Blood eosinophils and serum IgE as predictors for prognosis of interferon-gamma therapy in atopic dermatitis

BACKGROUND: Interferon-gamma (IFN-gamma) therapy has been reported to be effective in atopic dermatitis. However, IFN-gamma therapy in atopic dermatitis has not yet been well established. In this study, immunologic variables were evaluated as predictors for the prognosis of IFN-gamma therapy in atopic dermatitis. METHODS: Sixty-eight atopic dermatitis patients were each treated 18 times with 2 x 10(6) units/m2 IFN-gamma. Blood IgE level, eosinophil percentage, eosinophil count, and levels of IFN-gamma, interleukin-4 (IL-4), IL-5, and IL-10 were investigated. According to clinical responses, patients were classified into three groups: patients with improved clinical severity scores of over 20% were included in group A; those with improved scores of 20% or less in group B; and those with no improvement in group C. RESULTS: Serum IgE levels and blood eosinophil percentages were the lowest in group A. Most atopic dermatitis patients with an eosinophil percentage over 9% and IgE level over 1500 IU/ml did not respond to IFN-gamma therapy. Initial IL-10 levels were the highest in group A. IL-4 levels in group A, and IL-5 and IL-10 levels in all groups were significantly decreased by IFN-gamma therapy. CONCLUSIONS: IFN-gamma therapy may be recommended for atopic dermatitis patients with blood eosinophil percentages less than 9% and serum IgE levels less than 1500 IU/ml.     

Early BCG vaccination and development of atopy

BACKGROUND: The increase in atopic diseases may be partly explicable by a decline of certain infectious diseases, or changes in childhood vaccination programmes, or both. We investigated whether BCG vaccination against tuberculosis influences the development of atopy. METHODS: We did a retrospective cohort study of 216 children with atopic heredity, born in Stockholm between 1989 and 1992, who received BCG vaccination when they were younger than 6 months, and 358 age-matched controls who had not been vaccinated. Both groups attended Sachs' Children's Hospital, Stockholm, Sweden, during 1995-96 for assessment of atopic history and clinical signs of atopic disease. All children also underwent skin-prick testing (SPT) and serum was analysed for allergen-specific IgE antibodies. Serum from parents was also analysed for IgE antibodies. FINDINGS: 77 (36%) children in the BCG group and 145 (41%) in the control group had a positive history or clinical signs of atopic disease. In the vaccinated group, 26 (12%) children had one or more positive SPT, and 61 (31%) had circulating allergen-specific IgE antibodies, whereas in the control group, the numbers were 35 (10%) and 84 (27%) respectively. Atopy was confirmed by serology in parents of almost two-thirds of the children in each group. Other risk factors for atopic disease were evenly distributed between the two groups. INTERPRETATION: Early BCG vaccination in children with atopic heredity does not seem to affect the development of atopic disease before school age.     

Defective neutrophil chemotaxis and hyperimmunoglobulinemia E-a reversible defect?

An eleven-month-old boy is presented with chronic atopic dermatitis and recurrent infections of the skin and respiratory tract, including subcutaneous abscesses. Immunological studies disclosed a neutrophil chemotactic defect, blood eosinophilia and serum hyper IgE. The clinical and analytical data are similar to those of patients previously dermatitis reversed the chemotatic defect, the blood eosinophilia and the clinical symptoms.     

Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents

BACKGROUND: The double-blind, placebo-controlled food challenge (DBPCFC) is the "gold standard" for diagnosis of food hypersensitivity. Skin prick tests and RASTs are sensitive indicators of food-specific IgE antibodies but poor predictors of clinical reactivity. Previous studies suggested that high concentrations of food-specific IgE antibody were predictive of food-induced clinical symptoms. Because the CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) provides a quantitative assessment of allergen-specific IgE antibody, this study was undertaken to determine the potential utility of the CAP System FEIA in diagnosis of IgE-mediated food hypersensitivity. METHODS: Sera from 196 patients with food allergy were analyzed for specific IgE antibodies to egg, milk, peanut, soy, wheat, and fish by CAP System FEIA. Sera were randomly selected from 300 stored samples of children and adolescents who had been evaluated by history, skin prick tests, and DBPCFCs. The study population was highly atopic; all patients had atopic dermatitis, and approximately 50% had asthma and allergic rhinitis at the time of initial evaluation. The performance characteristics of the CAP System FEIA were compared with those of skin prick tests and the outcome of DBPCFCs or "convincing" histories of anaphylactic reactions. RESULTS: The prevalence of specific food allergies in the study population varied from 22% for wheat to 73% for egg. Allergy to egg, milk, peanut, and soy accounted for 87% of confirmed reactions. The performance characteristics of skin prick tests and CAP System FEIA (egg, milk, peanut, fish) were comparable, with excellent sensitivity and negative predictive accuracy but poor specificity and positive predictive accuracy. The performance characteristics of the CAP System FEIA for soy and wheat were poor. For egg, milk, peanut, and fish allergy, diagnostic levels of IgE, which could predict clinical reactivity in this population with greater than 95% certainty, were identified: egg, 6 kilounits of allergen-specific IgE per liter (kU[A]/L); milk, 32 kU(A)/L; peanut, 15 kU(A)/L; and fish, 20 kU(A)/L. CONCLUSIONS: When compared with the outcome of DBPCFCs, results of CAP System FEIA are generally comparable to those of skin prick tests in predicting symptomatic food hypersensitivity. Furthermore, by measuring the concentrations of food-specific IgE antibodies with the CAP System FEIA, it is possible to identify a subset of patients who are highly likely (>95%) to experience clinical reactions to egg, milk, peanut, or fish. This could eliminate the need to perform DBPCFCs in a significant number of patients suspected of having IgE-mediated food allergy.     

Atopic dermatitis

Atopic dermatitis is an important manifestation of the atopic diathesis with increasing incidence. The average lifetime prevalence in Switzerland is about 13%. The skin disease is characterised by severe itching, eczematous skin lesions with often distinctive distribution, dryness of the skin and a personal of family history of atopic diseases. The following article summarises some clinical, epidemiological, therapeutical and pathogenetical aspects of atopic dermatitis. Studies from the allergy unit of Zurich contributed to a better understanding of the disease. Thus, Storck was contributing various studies about neurovegetative and circulatory dysregulations in patients with atopic dermatitis. Furthermore, he already realised in 1955 a relation between exacerbations of eczema and the sensitisation to inhalatory allergens. Schnyder demonstrated that asthma, rhinitis and atopic dermatitis have the same genetic background and Wüthrich contributed important data about the natural history of the disease and the occurrence and relevance of total and specific IgE antibodies.     

Induction of atopic dermatitis by inhalation of house dust mite

BACKGROUND: The pathogenetic role of house dust mite in atopic dermatitis remains controversial. Recent studies have shown that intensive epicutaneous contact of house dust mite allergen with premanipulated skin may induce dermatitis. It is, however, uncertain whether such conditions are met during natural contact with house dust mite. In the past, allergen inhalation has been suggested to induce exacerbation of atopic dermatitis. The aim of this study was to investigate whether dermatitis could be induced in patients with atopic dermatitis by inhalation of house dust mite. METHODS: Twenty patients with atopic dermatitis underwent bronchial provocations with house dust mite. Challenge tests were performed with four concentrations of a standardized house dust mite extract in a double-blind, randomized, placebo-controlled fashion. Spirometry was performed, and FEV1 was measured before and after each challenge dose. Changes in severity or localization of itching or erythema were recorded. RESULTS: In nine of 20 patients with atopic dermatitis bronchial challenge with house dust mite induced unequivocal skin symptoms after 1.5 to 17 hours. Pruritic erythematous lesions on noninvolved sites together with exacerbations of existing lesions were seen in three patients. Three patients had an exacerbation only, and three other patients had new lesions only. In eight of nine patients with house dust mite inhalation-induced dermatitis, skin symptoms were preceded by an early bronchial reaction. All patients with house dust mite-induced dermatitis had a history of asthma, and as a group they had a higher mean blood total IgE level compared with the "negative skin responders." One patient had pruritic erythema on the placebo challenge day, without a preceding bronchoconstrictive reaction. The number of patients who had a skin response on the house dust mite challenge day was significantly higher than the number of patients who had a skin response on the placebo day (p = 0.011 [Prescott's test]). CONCLUSIONS: The respiratory route may be relevant in the induction and exacerbation of dermatitis in a subset of patients with atopic dermatitis who have early bronchial reactions after house dust mite inhalation, a history of asthma, and an elevated blood total IgE level. Furthermore, these findings suggest a possible causal relationship between bronchial reactions and skin reactions.     

Candida albicans sensitization in patients with atopic bronchial asthma and atopic dermatitis

Candida albicans, a component of normal human microflora, can induce synthesis of specific IgE-antibodies in patients with atopic bronchial asthma and atopic dermatitis. The study included 25 patients with atopic dermatitis sensitized to C.albicans and 23 patients with atopic dermatitis non-sensitized to C.albicans. The sensitization was determined by the skin test and enzyme immunoassay. The patients had the history of atopic dermatitis exacerbation after taking food containing baking yeasts. Atopic dermatitis with sensitization to C.albicans is characterized by severe course correlating with the following indices: high total IgE (r = 0.6), level of IgE antibodies to C.albicans (r = 0.6), level of serum IgG (r = 0.46) and IgA (r = 0.33). Contrary to adults, children with sensitization to C.albicans had decreased relative number of CD4+, CD8+ and CD72+ of lymphocyte subpopulations. Thus, sensitization to C.albicans manifests in severe atopic dermatitis which in children is often associated with immune deficiency.     

Apheresis platelets: emerging issues related to donor platelet count, apheresis platelet yield, and platelet transfusion dose

The prevalence of atopic dermatitis and other allergic diseases is increasing in industrialized countries. Today we know that atopy is conditioned genetically, but the development of the atopic phenotype requires environmental factors. It is believed that the genetic factors have not changed and that the increased prevalence is due to the increase in exposure to allergenic and non-specific environmental factors. The potential for sensitization is greater in the early years of life, so it is necessary to reduce harmful environmental exposure at these ages. Atopic clinical manifestations develop sequentially, in many cases beginning with atopic dermatitis in the early months of life. We know that children with atopic dermatitis present non-specific bronchial hyperreactivity (58 to 82%), which is a risk factor for the later development of asthma. The presence of specific bronchial hyperreactivity for mites in atopic dermatitis with mite sensitization also has been described, and it has been demonstrated that signs of eczema can develop or become exacerbated by airway exposure during bronchial challenge tests. The evolution from atopic dermatitis to asthma is a possibility that must be kept in mind. Patients should be followed-up and study of hyperreactivity and sensitization to allergens should be carried out in order to prevent the development of clinical symptoms. Prevention should include pneumoallergens, food allergens, and non-specific environmental risk factors, such as parental smoking (particularly mothers), pollution inside and outside the home, etc. Prevention is particularly important in children at risk of allergy, as determined by a family history among first-degree relatives, as well as the presence of atopic dermatitis, particularly of early onset, because these patient are most at risk of developing bronchial asthma in later years. At present, pharmacological prevention is being studied, without overlooking environmental prevention, in children at high risk of atopic disease for the purpose of preventing chronic inflammations that will condition their future as adults. In our daily clinical experience, atopic dermatitis is responsible for 8% of visits to a pediatric allergology unit. We emphasize that 62.5% of our patients with dermatitis are referred when they already have bronchial asthma, which represents an important delay in diagnosis with respect to the onset of symptoms.     

Abnormal vascular reactions in atopic dermatitis

Vascular reactions to mechanical stroking, topical application of nicotinic acid ester, and methacholine chloride were examined in both the normal and abnormal skin of 100 patients with atopic dermatitis and 20 patients with allergic contact dermatitis. White dermographism, nicotinic acid blanching, and delayed blanch with methacholine consistently occurred in areas of skin with eczematous change of patients with atopic dermatitis and those with allergic contact dermatitis. Normal skin of atopic patients did not show the abnormal vascular reactions. It is suggested that white dermographism, nicotinic acid blanching, and delayed blanch with methacholine seen in atopic dermatitis are secondary phenomena that give no definite information concerning the diagnosis of this disease.     

Relationship between interferon-gamma, interleukin-4 and IgE production of lymphocytes from hen's egg-sensitive patients

We measured in vitro interferon-gamma, interleukin-4 and IgE production of peripheral blood mononuclear cells stimulated with ovalbumin. Interferon-gamma in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells from hen's egg- sensitive patients with atopic dermatitis was significantly higher than that of healthy children or hen's egg-sensitive patients with immediate symptoms. Furthermore, in patients with atopic dermatitis who were sensitive to hen's egg and patients with immediate symptoms, there was an inverse relationship between interferon-gamma and IgE production (r = -0.535, p <0.05), and significant correlation was found between interleukin-4 and IgE production (r = 0.802, p <0.05). For the above reasons, IgE synthesis of ovalbumin-stimulated peripheral blood mononuclear cells may be suppressed by interferon-gamma in patients with atopic dermatitis. In contrast, in patients with immediate symptoms, interleukin-4 may play a major role in the pathogenesis of increased IgE production.     

Pathogenicity and lethality of a minute intestinal fluke, Neodiplostomum seoulense, to various strains of mice

Atopy is a genetically determined disorder that affects 10%-20% of the population. Many symptoms of patients with atopy (allergic rhinitis, conjunctivitis, asthma, and anaphylaxis) result from events occurring after crosslinking of cell-bound IgE by per se innocuous environmental antigens. The frequently raised hypothesis that autosensitization can also be a pathogenetic factor in atopy, gained support by our recent demonstration of IgE antibodies against human proteins in atopic dermatitis patients. To unravel the molecular nature of IgE-defined autoantigens, we used serum IgE from atopic dermatitis patients to screen a human epithelial cDNA expression library. One of the cDNA-encoding IgE-reactive products contained 1501 bp of a 2274 bp open-reading frame finally identified by sequence analysis of two additional cDNA clones resulting from oligonucleotide screening. The IgE-defined autoantigen, designated Hom s 1, exhibited an almost complete sequence identity with a recently described antigen recognized by cytotoxic T cells of a squamous cell carcinoma patient. Purified recombinant Hom s 1 specifically bound IgE from patients with severe atopy. When used as immunogen in rabbits, recombinant Hom s 1 gave rise to an anti-serum that reacted with a cytoplasmic protein exhibiting a broad cellular and tissue reactivity (skin, lung > gastrointestinal tract > muscle, brain) and identified a 55 kDa protein in blotted serum IgE preparations. The attractive possibility remains that the Hom s 1-triggered IgE response contributes to the events resulting in allergic tissue inflammation. If so, the respective recombinant molecule may serve as a paradigmatic tool for the diagnosis and treatment of patients with "intrinsic" atopy.     

A mutation (IVS8+0.6kbdelTC) creating a new donor splice site activates a cryptic exon in an Alu-element in intron 8 of the human beta-glucuronidase gene

BACKGROUND: Allergen-specific IgE antibodies have been considered to play an important role in the pathogenesis of atopic asthma. However, studies on allergen-specific IgE antibodies in airway secretion from asthmatic patients are very rare compared with those in serum. OBJECTIVES: The present study was undertaken to determine whether induced sputum might provide a useful method for analysing allergen-specific IgE antibodies in airway secretions from asthmatic patients. METHODS: Specific IgE antibodies to house dust mite (HDM) antigen were measured in induced sputum from 10 HDM-sensitive asthmatic patients and 12 non-allergic controls by enzyme-linked immunosorbent assay. HDM-specific IgE was regarded as positive when the absorbance value was higher than mean + 2SD of controls. Their antigen-binding characteristics were determined by immunoblot analysis. RESULTS: HDM-specific IgE was positive in induced sputum from seven of 10 HDM-sensitive asthmatics. The IgE binding to HDM antigen could be inhibited by fluid phase HDM antigen in a dose-dependent manner, not by mugwort antigen. Treatment of induced sputum with dithiothreitol decreased the antigen-specific bindings, and increased the non-specific bindings on the measurement of HDM-specific IgE. These effects were significant in a concentration of dithiothreitol greater than 0.05%. Immunoblot analysis revealed that HDM-specific IgE antibodies in induced sputum recognized the HDM antigens with molecular weights of 42, 34, 32, 25 and 14 kDa. These antigen binding characteristics were similar to those in serum. CONCLUSION: We conclude that analysis of induced sputum is a useful non-invasive method for studying allergen-specific IgE antibodies in airway secretion from asthmatic patients.     

Interleukin 4, total and allergen-specific immunoglobulin E antibodies in the blood of individuals with an atopic constitution

INTRODUCTION: The recently published data suggest that atopic patients have an enhanced ability to produce IL-4, even in response to antigens other than common environmental allergens or helminthic components. This aberrant IL-4 production by Th cells may be one of the immune alterations encoded by nonMHC genes in the control of basal IgE level [1-7]. The existence of atopen-CD4+ T cell clones that have diverse repertoires might be relevant for aetiopathogenesis of atopic diseases [8-10]. Being subjected continuously to the environmental antigens (allergens), the immune system, especially T cells, is permanently activated and stimulated in response to that challenge. Due to that, substantial amount of diverse cytokines (and their soluble receptors) could be found in the serum. Accordingly, it could be expected to find raised serum IL-4 concentration in atopic persons. In this study we investigated concentrations of IL-4, total IgE and allergen-specific IgE in sera of atopic persons susceptible to pollen allergens. The main goal was to estimate whether the immunologic profile of atopics is defined by increased serum concentration of IL-4 apart from total and allergen-specific serum IgE. METHODS: Patients. We selected 9 atopic patients in the range of 19-35 years, susceptible to grass or weed pollens and suffering from allergic rhinoconjuctivitis. There were 6 females and 3 males (mean age 31.2 years). Atopic allergy was proven by clinical history, skin prick test and by means of in vitro test (positive serum allergen-specific IgE antibodies, RAST/radioallergosorbent tests [11]. As controls we randomly selected B blood donors (6 females, 2 males, mean age 31.3). Study design. The study was carried out from August till September 1995. None of selected patients had previously accomplished allergen-specific immunotherapy nor had been medicated by corticosteroids (topic or systemic) [12-15]. Selected persons were not allowed to take medications such as antihistamines, beta-2 agonists or tricyclic antidepressants at least 10 days prior to the study. We performed in vitro tests for determining concentrations of IL-4, total and pollen-specific serum IgE. Sera were sampled in the morning and were stored frozen at -20 degrees C until analysis. Determination of IL-4, total and allergen specific IgE in serum. Interleukin-4 measurement was carried out in blind fashion with an ELISA kit (Intertest-4 ELISA, Genzyme, Cambridge) according to the manufacturer's instructions. A reference curve was obtained by plotting the IL-4 concentration of several standard dilutions versus an absorbency. The determination limit was 0.045 pg/ml. For determining total serum IgE we used commercially available enzyme immunoassay (EIA Phadezym IgE PRIST, Pharmacia, Uppsala). Normal values was up to 120 IU/L (international unit per ml). Allergen specific IgE was determined by semiquantitative EIA method (RAST Phadezym, Pharmacia, Uppsala) and expressed in Phadebas RAST Unit (PRU) according to standard curve done by manufacturer. Study was carried out after approval of the Ethic Committee of our Hospital and with the obtained patients consents. For statistical analysis we used nonparametric tests (U-test and the Spearman rank correlation). For all comparisons, statistical significance was considered to be present if p < 0.05. RESULTS: Among selected patients, 4 persons had high concentration of serum IgE antibodies (RAST class 4) against grass pollens, two persons had IgE-specific (RAST, class 4) to weed pollens and 2 patients had IgE antibodies (RAST class 4) against weed and grass pollens simultaneously. RAST of class 3 was registered in the serum of one person. Registered serum total IgE, allergen-specifc IgE and IL-4 are shown in Table 1. Serum IL-4 was significantly higher in atopics (U-test, SR 43.53, p.05) as well as total IgE (ER 493, p.05). In atopics, IL-4 was not in correlation with either total or allergen-specific IgE (IL-4 versus total IgE, p = +0.190;     

Effects of reconstructive surgery for left ventricular anterior aneurysm on ventriculoarterial coupling

Microbial agents are known to play a significant role in aggravating allergic diseases. Recently described viral and bacterial superantigens represent one important strategy by which infectious agents can stimulate the immune response. In previous work, we reported that the staphylococcal toxin toxic shock toxin-1 (TSST-1), a prototypic superantigen, induces in vitro total IgE synthesis after cross-linking T and B cells. This study was carried out to establish a potential link between superantigens and the enhanced IgE response to specific allergens in allergic patients. Peripheral blood mononuclear cells from atopic patients were isolated during and outside the pollen allergen season and stimulated with TSST-1, a prototypic superantigen. Total IgE and interferon-gamma production were measured in supernatants of these cultures. Outside the pollen season, TSST-1 significantly increased total IgE production only in the presence of exogenous interleukin-4, whereas during the pollen season IgE production was significantly enhanced without the need of exogenous interleukin-4. This increase in the absence of exogenous interleukin-4 was associated with significantly lower interferon-gamma production by peripheral blood mononuclear cells stimulated by TSST-1 during the pollen season. Moreover, TSST-1 stimulation of peripheral blood mononuclear cells from inhalant allergic patients was followed by an increased production of allergen-specific IgE that was restricted to the allergen to which the patient was allergic and recently exposed. In addition, TSST-1 induced on B cells the expression of B7.2, a molecule that has recently been demonstrated to enhance T helper 2 responses and to be involved in IgE regulation. This study, by demonstrating that superantigens can augment allergen-specific IgE synthesis and B7.2 expression, provides a mechanism by which microbial superantigens may modulate allergic responses.