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Atopic dermatitis (AD) patients mount IgE antibody responses to a variety of environmental allergens and also to autoantigens. We analyzed serum samples from four AD patients who had received oral cyclosporine A (CyA) treatment for up to 17 months regarding IgE autoreactivity to nitrocellulose-blotted human epithelial cell extracts and IgE levels to environmental allergens by quantitative ImmunoCap measurements. Skin inflammation was assessed by SCORAD. During full-dose treatment, a strong reduction in T-cell-mediated skin symptoms was observed which reappeared when CyA treatment was reduced or stopped. The intensity of IgE autoreactivity seemed to follow skin inflammation as it was reduced during full-dose treatment and increased upon inflammation. Interestingly, IgE levels to exogenous allergens were boosted by allergen exposure, declined thereafter, and seemed to be unaffected by CyA. Our data thus indicate that allergen-specific IgE production is boosted by allergen contact and cannot be reduced by CyA-mediated T-cell suppression., (© 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background: Because of changing world demographics, the elderly population is steadily increasing. Few studies have assessed the prevalence of atopy and allergic diseases in elderly persons with objective measures. The aim of this paper is to describe the prevalence of atopy, self-reported allergic rhinitis and doctor's diagnosed asthma in persons over the age of 60 in Switzerland., Methods: The cross-sectional examination of the Swiss Study on Air Pollution and Health in Adults (SAPALDIA 1), performed in 1991, included 9,651 adults aged 18-60 years. In 2001-2002 the same subjects were invited for a follow-up examination (SAPALDIA 2). Serum samples collected at baseline and follow-up were tested for specific IgE sensitization with the Phadiatop® (Phadia, Uppsala, Sweden, now Thermo Fisher Scientific) assay containing a mixture of common respiratory allergens (grass, birch, mugwort, Parietaria and olive pollen, dog, cat, horse, Cladosporium herbarum, house dust mite and flour mite). Atopy was defined as a positive result in the Phadiatop test according to guidelines by the manufacturer. The prevalence rates of atopy, self-reported allergic rhinitis and doctor's diagnosed asthma were evaluated by sex and age group (≤60 or >60 years)., Results: 7,667 subjects (men = 3,692/women = 3,975) participated in the follow-up by responding to a detailed questionnaire (80% of SAPALDIA 1 participants). Phadiatop results were available for 5,835 participants (men = 2,839/women = 2,996). Prevalence rates of atopy (Phadiatop positive) were 36.4% in men aged ≤60 years versus 26.2% in men aged >60 years and 30.6 and 18.1% in women, respectively (both p < 0.001). Prevalence rates of self-reported allergic rhinitis in subjects >60 years old were 13.0% for men and 15.4% for women (p = 0.12), and for doctor's diagnosed asthma 6.6% versus 7.6%, respectively (p = 0.40). Both rhinitis and asthma prevalences were higher in persons <60 years. The results were not sensitive to potential bias from nonparticipation at follow-up as demonstrated by imputation of sex- and age-specific allergic rhinitis and asthma among nonparticipants., Conclusions: According to our estimates, the prevalence of allergic rhinitis among persons aged between 60 and 70 years in Switzerland in the present cohort is of the order of 13-15% and should not be underestimated, although it is lower than in age groups ≤60 years., (Copyright © 2013 S. Karger AG, Basel.)

Background: Autoreactivity of patients with atopic dermatitis (AD) to human proteins has been postulated as a decisive pathogenetic factor for AD., Objective: In this study, it was investigated whether the stress-inducible enzyme manganese superoxide dismutase (MnSOD) of human and fungal origin might act as an autoallergen in atopic dermatitis., Methods: Patients with AD (n = 69; mean SCORAD [SCORing Atopic Dermatitis], 27) and other inflammatory skin diseases as well as with inhalant allergies were investigated. The presence of specific IgE against recombinant MnSOD of fungal and human origin and the fungal extracts of Aspergillus fumigatus and Malassezia sympodialis was measured by CAP, ELISA, skin prick test, and in subset of patients also by atopy patch tests (APTs) and PBMC proliferation assays. Cross-reactivity between allergens was determined by CAP inhibition. The presence of MnSOD in human skin in various inflammatory skin conditions was investigated by immunohistochemistry., Results: Specific IgE antibodies against human MnSOD correlating with the disease activity were found in 29 out of 67 patients with AD. The human protein was able to induce in vitro T-cell reactivity and eczematous reactions in APT in MnSOD-sensitized patients with AD. MnSOD was upregulated in various inflammatory skin reactions and APT skin specimens. Cosensitization to structurally related and cross-reacting fungal MnSOD and the skin-colonizing yeast M sympodialis was observed in all patients sensitized against human MnSOD., Conclusion: Human MnSOD may play a role as an autoallergen in a subset of patients with AD, including nonatopic eczema. By molecular mimicry leading to cross-reactivity such sensitization might be induced primarily by exposure to environmental fungal MnSOD of M sympodialis .

Background: Mugwort pollen is an important allergen source in hay fever and pollen-related food allergy. Little is known about the clinical relevance of the major mugwort allergen Art v 1 and its importance in allergy., Objective: In this study we aimed to investigate the allergenicity of mugwort extract compared with the allergenicity of native (n)Art v 1 and recombinant (r)Art v 1, one major allergen of mugwort, in vivo and in vitro., Methods: Thirty-two patients allergic to mugwort and 10 control subjects were investigated by means of skin prick and nasal provocation testing with different concentrations of mugwort extract, nArt v 1, and rArt v 1. nArt v 1 was purified from aqueous mugwort extract, and rArt v 1 was cloned, expressed in Escherichia coli, and then purified. The in vitro allergenicity was measured by means of ImmunoCAP, ELISA, ELISA-inhibition experiments, and T-cell proliferation assays., Results: nArt v 1 and rArt v 1 were able to elicit positive in vivo and in vitro reactions. The IgE-binding capacity, as determined by means of ELISA, was slightly higher for nArt v 1 than for rArt v 1, and both allergens were able to induce T-cell proliferation in sensitized patients. However, rArt v 1 elicited a reduced response in skin and nasal provocation tests compared with nArt v 1. Compared with mugwort extract, both nArt v 1 and rArt v 1 showed lower sensitivity in patients with mugwort allergy in vivo., Conclusions: Art v 1, either in its native or recombinant form, is able to induce allergic reactions in patients with mugwort allergy. rArt v 1 induced comparable humoral and cell-mediated responses in vitro but showed reduced in vivo allergenicity compared with biochemically purified nArt v 1.

Background: Banana is a frequent cause of food allergy, particularly in latex-sensitized patients., Objective: The aim of the study was to get insights in immunoglobulin (Ig)E antibody responses of patients with a history of allergic reaction to banana but not to latex., Methods: In four patients who complained about symptoms after banana consumption, skin prick tests (SPTs) with aeroallergens, latex, banana, avocado, and kiwi were performed. Total and specific serum IgE to birch pollen, rBet v 1 and rBet v 2, latex, banana, avocado, and kiwi were determined by the CAP method (Pharmacia Diagnostics, Uppsala, Sweden). Allergens were identified by immunoblotting with banana extract and recombinant banana profilin. Two patients underwent double-blind, placebo-controlled food challenges (DBPCFC) with banana., Results: All patients showed a positive SPT to banana, and three were IgE-CAP positive (> or = class 2). Two patients were also sensitized (SPT and CAP) to latex, avocado, kiwi, and birch pollen. In the immunoblot these two patients' sera reacted to 32- to 34-kDa proteins, which had already been described as major banana allergens. In both patients banana allergy was confirmed by DBPCFC. The third patient also had a sensitization to avocado, but not to latex or pollen. Immunoblot analysis detected a single band at 70 kDa. The fourth patient was sensitized to birch pollen, rBet v 1 and rBet v 2, but not to latex. Immunoblot analysis in this patient's serum was positive with recombinant banana profilin., Conclusions: The relevance of banana as a source of food allergy was confirmed in two patients by DBPCFC. In 1 of 2 patients, in whom banana allergy was not a consequence of latex sensitization, a 70-kDa protein was identified as a banana allergen, and in the other patient profilin was detected as a putative cross-reactive allergen.

Background: Allergy to persimmon (Diospyros kaki) is very rare and not yet confirmed by means of double-blind, placebo-controlled, food-challenge (DBPCFC). Thus far, specific IgE to this fruit and cross-reactivity to pollen and other foods has not been determined., Objective: The objective was to confirm allergy to persimmon in 3 patients with an according personal history and to characterize allergens and cross-reactivity of specific IgE antibodies to pollen and food allergens. One patient reacted with pruritus, penis edema, urticaria, and asthma; the second reacted with nausea and vomitus; and the third reacted with rhinoconjunctivitis, asthma, and stomachache after ingestion of persimmon., Methods: Patients underwent skin prick testing with routine allergens, latex, persimmon, and other foods. Allergy to persimmon was confirmed by means of a DBPCFC. Specific serum IgE levels were measured with CAP-FEIA and the enzyme allergosorbent test (EAST) method. EAST and immunoblot inhibitions were carried out with persimmon; birch, grass, and ragweed pollen; latex; and N-glycans as inhibitors., Results: All patients had positive skin test responses, DBPCFC and specific IgE assays to persimmon. Blot and EAST inhibition assays revealed IgE to cross-reactive profilin in one patient and IgE to cross-reacting carbohydrate determinants in all patients., Conclusions: This is the first report on 3 cases of allergy to persimmon verified by means of DBPCFC and detection of specific IgE. The sensitization is due to cross-reactive profilin and carbohydrate determinants.

Sera from 42 patients sensitive to birch pollen were investigated in a pilot study with the new Allergodip screening dipstick for cross-reactive allergens (Allergopharma). The dipstick contained nine separate allergen pads with extracts from birch pollen, hazel pollen, alder pollen, apple, hazelnut, carrot, peach, mugwort pollen and celery root (celeriac), together with negative and positive controls. The results of the test were assessed visually and classified in Allergodip classes 0-4 and compared with the results from the Pharmacia CAP method and with the symptoms reported by the patients. The Allergodip method showed good reproducibility for color intensity and visual assessment. The correspondence between Pharmacia CAP and Allergodip was high for tree pollens (98-100%) and medium for mugwort pollen, celery, hazelnut and carrot (60-71%). Apple and peach showed only 24% and 42% concordance, respectively The sensitivity and specificity of Allergodip and Pharmacia CAP differed in regard to food symptoms. However, they were always within the range of earlier publications. As a consequence of this study, the manufacturer of Allergodip has improved the apple allergen extract by adopting a low temperature extraction procedure. Subsequent measurements with sera from 14 apple-allergic patients showed greatly improved concordance with both CAP measurements and symptoms (93% and 86%, respectively).

Background: Clinical and population studies have shown that exposure and sensitization to allergens derived from furred pets, particularly cats, represent an important risk factor of allergic respiratory disease and also a significant risk factor for asthma., Objective: In the framework of the multicenter European Community Respiratory Health Survey an analysis of the association of current and childhood exposure to cat with atopic sensitization to cat was conducted., Methods: This study included cross-sectional data from 35 centers representing 16 countries. Altogether, 18,097 subjects were included, of whom 13,509 (75%) provided a blood sample for the measurement of specific IgE. Exposure data and data for potential confounders were extracted from an interviewer-led questionnaire., Results: The prevalence of sensitization to cat (serum specific IgE >0.35 kU/L) was 9%. Among those who did not report allergic symptoms in the presence of pets or house dust, those who owned cats were significantly more likely to be sensitized to cats than were those who did not (odds ratio [95% confidence interval] 1.57 [1.20-2.06]. Childhood exposure to pets including cats was associated with lower sensitization to cats in adulthood, particularly among those with a positive family history of atopy (odds ratio [95% confidence interval] 0.68 [0.51-0.93]. Positive correlations were found between the community prevalence of cat and the prevalences of sensitization to cat, respiratory symptoms, physician-diagnosed asthma, and current asthma medication., Conclusions: Current cat ownership represents a significant risk for sensitization to cat if cats are allowed indoors. Our results support the hypothesis that childhood exposure to pets, including cats, might modulate immunologic mechanisms and reduce sensitization to cat in adulthood. The significant correlation found between the community prevalence of cat ownership and community prevalence of specific sensitization to cat represents the first documentation of such a relationship.

The present study deals with the detailed investigation of the IgE antibody response of a gum arabic-allergic patient. The patient showed multiple serologic and skin test sensitizations to a range of pollen, other inhalants and foods, and bee venom, and to the recombinant allergens Bet v 1 and Bet v 2. Moreover, the patient's serum reacted strongly to gum-arabic extract. The NaIO4-treated and thus deglycosylated extract showed no binding to IgE. In contrast, removal of the protein backbone by basic hydrolysis did not deplete the IgE reactivity. Therefore, it is concluded that the gum arabic-specific IgE antibodies of this patient were mainly directed against the carbohydrate fraction of this material. In IgE-inhibition assays, cross-reactions occurred in the range of 60% between gum arabic and known immunogenic N-glycans containing alpha1-3-linked fucose. Since the inhibition graphs were not parallel and the inhibition was not complete with heterologue antigens, the cross-reacting epitopes of gum arabic appeared to be different from the latter well-known cross-reactive carbohydrate determinants (CCD). Inhibition may have been caused by a partial immunologic identity of the investigated carbohydrate moieties. A strong IgE response to the fucose-containing glycan from bromelain was measured in a glycan ELISA that utilizes purified glycopeptides at the solid phase. This response, which may explain the multiple sensitizations without clinical significance diagnosed in the patient, could originate from inhalation of pollen, which is known to contain similar glycans, or from occupational sensitization during work as a baker and confectioner. Since the gum-arabic protein showed only very weak participation in the IgE reactivity, the clinical symptoms of the patient caused by gum arabic may be attributed to carbohydrate epitopes. Due to the repetitive polysaccharide sequence of gum arabic, several epitopes for the cross-linking of IgE should exist.

Mugwort and birch pollen allergy are frequently associated with IgE-mediated hypersensitivity to celery and spices. We analyzed 22 sera from patients with the mugwort-birch-celery-spice syndrome for IgE binding to the spices pepper and paprika by immunoblotting. Immunoblot results revealed two major allergens of 28 and 60 kDa in pepper and a 23-kDa allergen together with allergens of higher molecular weight in paprika. In immunoblot-inhibition studies, crude mugwort, birch pollen, and celery extracts significantly reduced the IgE binding to pepper and paprika allergens. However, no inhibition was achieved with rBet v 1 and rBet v 2, suggesting that no homologs of these birch proteins act as allergens in pepper or paprika extracts. N-terminal sequence analysis of the 14- and 28-kDa pepper and 23-kDa paprika allergens revealed no homology to known allergens. The 28-kDa pepper allergen showed homology to a wheat germin protein, and the 23-kDa paprika allergen was identified as a homolog of a osmotin-like or pathogenesis-related protein in tomato. Therefore, we conclude that the IgE cross-reactivity in the mugwort-birch-celery-spice syndrome to the spices pepper and paprika is not caused by homologs of Bet v 1 and profilin. N-terminal amino acid sequence analysis of the main allergens in pepper and paprika indicate a relation to frequently occurring plant proteins.

Background: Symptoms elicited by IgE-mediated food allergy range from mild local to severe systemic reactions. Allergens in spices are particularly dangerous due to their hidden presence in many dishes., Objectives and Methods: According to clinical observations, mugwort and birch pollen allergy, and hypersensitivity to spices are frequently associated, but the crossreacting compounds were not defined so far. We tested sera of 15 patients who experienced adverse reactions to spiced food and characterized their IgE-binding patterns on anise, fennel, coriander and cumin extracts through immunoblot and inhibition experiments., Results: The use of anti-Bet v 1 (MoAb) and anti-profilin (rabbit) antibodies revealed the presence of crossreacting allergens in the tested spice extracts. Inhibition experiments showed that IgE-binding to allergens in Apiaceae spices could be blocked by preincubation of sera with rBet v 1 or rBet v 2 (birch profilin). Moreover, we detected crossreacting allergenic molecules in the molecular weight range of 60 kDa. IgE-binding to spice allergens occurred only with sera of 10/15 (66%) patients with allergy to pollen (birch, mugwort) and/or celeriac. In five out of 15 (33%) patients with a history of adverse reaction to spices, but without pollen and celeriac allergy, no IgE-binding to any spice protein could be demonstrated. It is possible that these clinical reactions could be elicited by other types of hypersensitivity (Type II, III, IV), however, as spices contain highly reactive substances, the symptoms may most likely be classified as food-intolerant., Conclusions: Bet v 1- and profilin-related allergens may, besides higher molecular weight allergenic molecules, be responsible for Type I allergy to anise, fennel, coriander or cumin, members of the Apiaceae.

Investigations on the mechanisms of IgE regulation in vitro have been conducted thus far in systems that allow the synthesis of total rather than specific IgE. To study the regulatory prerequisites of antigen-specific IgE antibody production, we have established a culture system that allows the generation of bee venom phospholipase A2-specific IgE and IgG4 antibodies. Allergen-specific IgE was induced by simultaneously activating T cells and B cells specifically with allergen and polyclonally with anti-CD2 and soluble CD40 ligand in the presence of IL-4. Additional stimulation of T cells through the CD2 activation pathway by two different anti-CD2 monoclonal antibodies enhanced both the allergen-specific and the total IgE and IgG4 responses. An optimal amount of allergen (0.1 ng/ml) resulted in the induction of both allergen-specific IgE and IgG4 antibodies. Higher antigen doses reduced allergen-specific antibodies and enhanced total isotype production. This differential regulation of allergen-specific and total isotypes reflects different allergen dose-dependent mechanisms in specific and polyclonal activation of T and B cells. Although both isotypes require IL-4 for initial induction, opposite regulatory effects by T cells were observed for IgE and IgG4 antibody expression. In peripheral blood mononuclear cell cultures stimulated with soluble CD40 ligand, IL-4, and phospholipase A2, stimulation of T cells with higher amounts of anti-CD2 enhanced IgG4 in parallel to increased IL-2 and interferon-gamma secretion but inhibited IgE synthesis. These results provide evidence for differential regulation of allergen-specific and total IgE and IgG4 by antigen concentration and demonstrate the pivotal role of T cells controlling the synthesis of the IgE and IgG4 antibody isotypes.

Within the framework of the SAPALDIA survey (Swiss study on Air Pollution and Lung Diseases in Adults), we studied the influence of sex, age and smoking habits on total serum IgE and allergen-specific IgE antibody concentrations (assessed by means of the Phadiatop test) and on the prevalence of hay fever. A total of 8,344 subjects aged 18-60 years, comprising 2,776 current smokers, 1,888 former smokers and 3,680 nonsmokers, were included in the study. Smokers had both a statistically significant (p<0.001) higher mean serum IgE concentration (geometric mean 39.7 kU/l), and a higher percentage (27.5%) of persons with elevated serum IgE (> 100 kU/l) than nonsmokers (27.2 kU/l; respectively 20.5%). The IgE level was significantly lower in women than men (p<0.001) in all smoking categories. The percentage of persons with positive atopic markers (positive Phadiatop test, positive skin prick tests to common inhalant allergens) and self-reported hay fever was significantly higher in nonsmokers than in smokers or former smokers. In Phadiatop positive (atopic) subjects, the IgE levels were highest, with a mean of 104.3 kU/l (99.0-109.8), and lowest in Phadiatop-negative nonsmokers at 27.2 kU/L (25.9-28.6). These findings correlate well with the current interpretation of total serum IgE values in screening for atopic diseases in adults (IgE < 20 kU/l: atopy improbable; IgE > 100 kU/l: atopy probable). In multivariate logistic regression models, the prevalence of positive Phadiatop tests, positive skin tests, and atopy decreased significantly with age. The odds of having a positive Phadiatop and skin test, or being atopic were found to decrease on average by 23.0, 21.1 and 21.0%, respectively, with every 10-year increase in age. With respect to smoking status, the odds ratios for the three atopic markers were significantly lower in current and former smokers than in nonsmokers. The prevalence of (self-reported) hay fever was highest in nonsmokers, intermediate in former smokers (odds ratio = 0.81, p<0.05) and lowest in current smokers (odds ratio = 0.76 in comparison to former smokers, p<0.01). The odds ratio of self-reported current hay fever decreased with age at an estimated average of 23% every 10 years. The decrease in former smokers might be slightly faster than in the other two categories. In conclusion, the present results demonstrated that tobacco smoking is associated with increased IgE levels and negatively related to atopy and hay fever. In addition, it is shown that atopy prevalence decreases with age.

Background: Allergy to celery is often associated with sensitization to birch and/or mugwort pollen., Objective and Methods: In a multi-centre study, sera from 23 patients suffering from type 1 allergy to celery and 15 patients with positive celery RAST but no clinical sensitization were compared. To examine whether cross-reactivity between celery and mugwort pollen includes cross-sensitization to birch pollen allergens, we determined cross-reacting structures in birch pollen, mugwort pollen and celery by means of immunoblotting. Inhibition studies were performed by preincubation of sera with extracts of birch pollen, mugwort pollen, and celery., Results: We identified three groups of proteins--homologues of Bet v 1 and birch profilin (Bet v 2) as well as a group of proteins with a molecular range of 46 to 60 kD--displaying IgE-cross-reactivity, which were shared by birch pollen and celery. Two of these groups of allergens (profilin and the 46 to 60 kD proteins) were also present in mugwort pollen. In this paper we demonstrate that most cross-reacting allergens present in mugwort pollen and celery can also be detected in birch pollen extract., Conclusion: Therefore we propose, from a serological point of view, to extend the mugwort-celery syndrome to the birch-mugwort-celery syndrome.

Objectives: The purpose of this study was to characterize the IgE binding components of celery root by immunoblot analysis and to investigate the cross-reactive nature of the allergens., Background: Sensitization to celery is very common in patients hypersensitive to mugwort pollen and birch pollen, and is due to cross-reactions of allergen-specific IgE antibodies. Recently, the pan-allergen profilin has been identified as an important cross-reactive allergen in celery, birch pollen and mugwort pollen. Very few data, however, on additional celery allergens are available., Methods: Sera of 38 patients with an isolated or combined sensitization to birch pollen, mugwort pollen, and celery were investigated by immunoblot and immunoblot inhibition techniques using celery extract and purified Bet v I, the major allergen from birch pollen. The selection of sera was based on serologic sensitization, independent of clinical manifestations. Celery profilin was affinity isolated and analyzed by immunoblotting with patients' sera as well as with rabbit polyclonal antiserum raised against celery profilin., Results: Only weak IgE binding occurred on celery immunoblots in the patient groups with a negative RAST to celery. Sera of 6/8 patients with a birch pollen/celery sensitization recognized a 16-kDa celery allergen that cross-reacted with Bet v I in immunoblot inhibition experiments. In the mugwort pollen/celery and birch pollen/mugwort pollen/celery patient groups, the sera of 6/16 patients contained IgE that bound to a 15 to 16-kDa double band identified as celery profilin. Furthermore, three sera of the birch pollen/mugwort pollen/celery group appeared to contain IgE antibodies against carbohydrate determinants., Conclusions: The 16-kDa Bet v I-related celery protein appears to be an important allergen for patients sensitized to birch pollen and celery. In contrast IgE binding to celery profilin appears to be more important in patients with an additional sensitization to mugwort pollen.

The hyper-IgE syndrome is characterized clinically by recurrent staphylococcal abscesses of the skin, lungs and other sites from infancy. Affected patients also have a pruritic dermatitis that differs in character and distribution from lesions of atopic dermatitis. Most lack other signs of atopic disease, develop persistent pneumatoceles and have osteopenia. Laboratory abnormalities include the consistent presence of marked hyperimmunoglobulinemia E and eosinophilia of blood, sputum and tissues. They may have other inconsistent abnormalities of humoral and cellular immune responses and sometimes of phagocytic cell chemotactic responsiveness. Other clinical problems reported in such patients have included lymphomas, cryptococcal meningitis and cutaneous fungal disease. An 18-year-old male patient with a variant of the hyper-IgE syndrome, which he had acquired after a measles attack at the age of 5 years, suffered from recurrent ulcerative dermatitis and lymph node abscesses. Immunological investigation revealed an excessively elevated total serum IgE level (46,850 IU/ml), the presence of specific IgE to staphylococci, and quantitative and functional deficiency of IgG2. Skin and serological (radioallergosorbent) tests to inhalant and nutritive allergens were negative. Differentiation from atopic dermatitis should be made, because a long-term antistaphylococcal regime not only improves skin lesions but hinders the occurrence of lung abscesses and pneumatoceles.

Serum IgE and IgG4 concentrations were determined in 102 children with atopic dermatitis (AD) of varying severity and activity. Total as well as specific IgE levels, determined by the radioallergosorbent test (RAST), were correlated with disease severity and the coexistence of atopic respiratory diseases. The IgG 4 levels of children with only AD, even in severe cases, were within the normal ranges of healthy children. In contrast, the IgG4 levels of children with both cutaneous and respiratory atopic manifestations were elevated, suggesting that IgG4 are probably associated with respiratory diseases but do not play any role in the pathogenesis of the skin disorder.

The concentrations of venom specific IgE (Phadebas-RAST) and IgG (Phadebas IgG-RAST) were monitored in sera of 22 patients with histories of systemic anaphylactic reactions following insect stings who underwent immunotherapy with venom extracts (bee venom and/or yellow jacket venom). Analysis of the immunological parameters during immunotherapy revealed great individual variation in the degree of response concerning both specific IgE and IgG antibodies. Nevertheless, four typical patterns of immune response could be found. The majority of the patients were able to produce high titers of IgG "blocking" antibodies without an IgE increase. Another group of patients had a marked rise in both specific IgG and IgE following the initial phase of hyposensitization. In contrast, one patient received venom injections without a significant IgG or IgE response. Finally, a small group of patients has a marked increase in specific IgE while synthesis of IgG was not observed. This IgE rise was the cause of systemic reactions in this group after the venom injections. Regular monitoring of venom specific IgE and IgG is useful in evaluating the degree of protection for the patient. Since an increasing IgG/IgE ratio must be obtained during immunotherapy, a knowledge of this relationship serves to adapt the individual treatment schedule.

Serum IgE concentrations were determined according to the radioimmunosorbent technique (RIST, Phadebas) on 116 adult patients with atopic dermatitis of varying severity and activity. Geometric mean IgE levels of patients with atopic dermatitis were significantly higher compared with the mean level of ninety-three non-atopic adult subjects without parasitic infestation. Severity of the atopic dermatitis was highly correlated to the levels of serum IgE. Severe chronic cases with ever-recurrent exacerbations show the most extreme values. In the moderate forms of atopic dermatitis, coexistent bronchial asthma causes a greater increase in the IgE values. Among the mild or abortive forms higher IgE levels were found in cases with allergic rhinitis than in the cases with 'pure' atopic dermatitis. Other findings in connection with IgE in atopic dermatitis are summarized. The pathogenetic significance of IgE in the cutaneous changes is briefly discussed.

The Radio Allergo Sorbent Test (Phadebas-RAST) is a recently developed radioimmunological in-vitro test for determining IgE specific serum antibodies in reaginic allergy. The overall correspondence between RAST and skin tests in 1,128 tests with a total of 19 allergens was 70.2%. The agreement between positive RAST and skin tests was 22.1%. In instances of disagreement the combination of a positive skin test and a negative RAST was much more frequent (24.1%) than the reverse (5,7%). The agreement between RAST and skin tests was 94.5% for cat epithelium, 89.3% for egg white, 86.2% for timothy pollen, 84.2% for milk, 80.3% for mite Dermatophagoides pteronyssinus, 78.8% for birch pollen, 71.9% for dog epithelium, 67.7% for horse dandruff, 57.3% for moulds and only 40.3% for house dust. Positive RAST results for atopic patients with respiratory allergy usually indicate a clinically relevant sensitization (positive case history or positive provocation test), while negative results do not rule out the possibility of significant sensitization. Circulating reagins were detected in 9.4% of the mite and 12.7% of the mould RAST, although the skin tests were negative. The greatest discrepancy between RAST and inhalation test results occurred with house dust (47% agreement, only 12% positive correlation). The RAST was negative in 53% of the cases with positive provocation tests. The first step in the diagnosis of allergy is still a thorough case history combined with careful prick and intracutaneous testing. When the case history and skin tests are in disagreement, RAST may be helpful as a supplementary test. In addition, the RAST may be useful in clarifying cases in which the patient is on continuous steroid or antihistamine therapy, as well as for children who are frightened of skin tests. If house dust asthma is suspected, it is advisable in all but a few instances to utilize the bronchial provocation test to confirm the diagnosis and for initiation of specific desensitization.

Thirty-five patients with ichthyosis were classified according to the clinical features, the genetic and histological findings, the association with manifestations of atopy and the result of the skin tests into the following three groups: (1) Autosomal dominant ichthyosis (ADI) with atopy (n = 13), (2) ADI without atopy (n = 17) and (3) X-linked ichthyosis (n = 5). Serum IgE levels were determined in patients and in a normal control group (n = 93) with the Phadebas-IgE-PRIST. The frequency of the association of ADI with atopy was with 44% in accordance with the literature reports. The geometrical means of the IgE values in the ADI-group with atopy were statistically significantly higher than in the ADI group without atopy (p less than 0.05) or in the control group (p less than 0,01). The increase of the IgE-levels in ichthyosis is due to the associated atopy.

The occurrence of allergic diseases is studied in a group of 56 Swiss children suffering from cystic fibrosis (CF). 27% of CF children showed allergic manifestations, and 61% of CF children had positive family history for atopic diseases. The occurrence of allergies is increased in homozygotes as well as in heterozygotes for CF. Total serum IgE values are clearly increased in atopic CF children, but also slightly elevated in CF patients without allergic manifestations. Occurrence of specific IgE (RAST) for the house dust-mite Dermatophagoides pteronyssinus, timothy grass pollen. Aspergillus fumigatus and Penicillium is summarized.

The serum IgE levels were determined according to the radioimmunosorbent technique (RIST), in 208 children aged between 1 and 14 years, with atopic diseases alone or in combination. Geometric mean IgE levels were significantly increased and rose progressively from the atopic dermatitis "alone" to the allergic rhinitis, the allergic asthma and the combination of asthma with rhinitis, with the highest values in patients where atopic dermatitis was combined with respiratory allergy. IgE levels rose slowly with age. For the atopy diagnosis in vitro, two criteria were chosen and compared: a fixed IgE-level of 100 U/ml, and one standard deviation below the geometric mean of the atopic children.

Fifty sets of twins (thirty monozygotic [MZ] and twenty dizygotic [DZ], of whom at least one twin had a history of atopy, were investigated by means of skin tests, RAST and IgE determinations. The concordance of atopies for MZ was, with 56.7%, significantly higher as compared with the DZ with 20%. The mean values of the log serum IgE level differences of MZ and DZ sets of twins was not statistically significant but the percentage distribution of the log serum IgE level differences showed a closer correlation of the IgE levels among MZ. The MZ sets do not show a better concordance in the specific reagin production, as measured by RAST or skin tests, than the DZ sets. These findings seemed to indicate that although the tendency of IgE production is genetically determined its specificity is governed mainly by environmental influences.

Two patients with positive formaldehyde RAST and 3 with positive phthalic anhydride RAST are described, of whom 3 presented with a typical history of occupational asthma and one had only work-related rhinitis. The fifth case with specific IgE antibodies to formaldehyde had only a domestic exposure-effect relationship; asthmatic symptoms had first started some weeks after renovation of the patient's apartment. Thus far, failing proof of specific IgE antibodies, a true allergic reaction to formaldehyde in particular has been doubted. Presenting respiratory symptoms were considered to be probably due to irritant effects. The reported cases indicate that formaldehyde and phthalic anhydride may also exert their effect through immunologic mechanisms.

The predictive value of diagnostic tests for the recognition and differentiation of allergic diseases of the immediate type has been evaluated on the basis of the results of a non-selective allergologic-pneumologic examination of the staff of an industrial bakery. Out of the 314 subjects tested, 22 (7%) had a respiratory allergy against flour (flour rhinitis and/or flour asthma), and 21 (6.7%) a preexistent atopic disease without actual symptoms of flour allergy. Thus the predominance of atopy in the group examined was 13.7%. A prick-multitest was carried out in all 314 subjects on each forearm and allowed simultaneous and easy application of twice eight test substances ("atopy-screening" and "bakery-line"). 50% of the bakers with flour allergy also showed positive skin tests with non-occupational inhalative allergens (housedust, housedust mite, pollen) while only 9.2% of the subjects without respiratory allergy to flour did so. 17.1% of the heavily exposed, asymptomatic bakers showed a positive immediate reaction to the highly sensitive intracutaneous test with wheat flour. Here the problem of latent sensitization arises. With histamine the prick-multitest resulted - compared to the intracutaneous test - in 1.6% "false negative" and 3.2% only questionably positive results. Furthermore, 6.1% of the subjects showed a strong, and 3.2% a very strong, nonspecific reaction to the control solution glycerin. Despite these restrictions the prick-multitest proved far superior to measurement of total serum IgE for screening of atopy. Technical improvements have been made in the meantime by the manufacturer. Specific IgE was detected in RAST screening in 59 of the 306 subjects who underwent blood tests. The geometric mean of total IgE values was only 75 U/ml, and for the RAST-negative subjects 23.3 U/ml, while their 95% confidence level was 225 U/ml. This logarithmic-normal distribution of the measured values, together with the excessive normal-atopic overlap, makes it impossible to lay the test cutoff point in a way which results in an acceptable relation between sensitivity and specificity. For the population examined the sensitivity of the total IgE measurement was already below 50% at a cutoff point of 80 U/ml, while the positive predictive value did not yet reach 50% at 160 U/ml. This diagnostic test is at present certainly used too often and without sufficient awareness of its very limited predictive value. As a screening method the RAST is too expensive. Furthermore, the problem of a latent sensitization also exists for the RAST.

Serum IgE concentrations, determined by two commercial kits (Phadebas RIST and PRIST) in 93 adult controls resulted in a geometrical mean value of 47 (RIST) and 35 U/ml (PRIST) respectively within a + 2 SD value of 195 and 331 U/ml respectively. The difference between the separated random samples is statistically significant (t = 3.79; p less than 1%), but the correlation is still fairly satisfactory (r = 0.79). In the lower regions the IgE values with RIST are as a rule a little higher than with the PRIST method. Surprisingly, one patient showed an extremely low IgE value (7 U/ml) with PRIST, but a considerably higher one (530 U/ml) with RIST. Such marked differences are found occasionally in the literature: heterophile antibodies against bovine gammaglobulin are regarded as responsible for the interference in the Sephadex system of RIST. As the reproducibility of the IgE determinations with the PRIST method is excellent (the correlation coefficient for two PRIST determinations was r = 0.93), and as PRIST allows much lower IgE estimates, this procedure should be given preference, particularly in pediatric patients. On the other hand, RIST must be used for the determination of extremely high values, as for instance in patients with severe atopic dermatitis or with parasitic infestations. In fact they can no longer be exactly evaluated by PRIST. Quality control of IgE serum determinations among twelve randomly chosen laboratories in Switzerland in 5 patients was satisfactory, with one exception. In the case of extremely high values, however, only a few laboratories try to determine the exact value. Indications of more than 500 U/ml were considered sufficient, with actual values amounting to 12,500 U/ml. It is also advisable to standardize the serum dilutions, the use of reference serum and the price. Finally, the indications for IgE determination are discussed. It is considered to have an important bearing on the differential diagnosis and prognosis of atopic diseases in infants and children.