IgE and IgG antibodies to Malassezia spp. yeast extract in patients with atopic dermatitis

The presence of immunoglobulins to Malassezia spp. surface proteins in the sera from patients with atopic dermatitis and healthy subjects was studied. It was found that 28% of 25 examined patients with atopic dermatitis had IgE antibodies to Malassezia spp. surface protein preparation. All patients and 5 healthy subjects had IgG antibodies to this preparation. The presence and concentration of specific IgE antibodies in patients with atopic dermatitis correlated with reverse titers of IgG antibodies to this preparation (r=0.782). The medians of values reciprocal to IgG antibody titers in patients with atopic dermatitis with and without specific IgE antibodies to the preparation and in healthy subjects were 64, 1024, and 16, respectively. The preparation derived from Candida albicans (candidine) and previously derived preparation from Malassezia did not cross-react. According to immunoblotting data, the preparation contains allergens presented by proteins with molecular weights 15, 36, 52-56, and 78.4 kDa.     

Quantitative assessments of IgG and IgE antibodies to inhalant allergens in patients with atopic dermatitis

Using antigen-binding radioimmunoassays, we have measured class specific antibodies against two major inhalant allergens, antigen P₁ from D. Pteronyssinus and Rye I from grass pollen, in sera from 69 patients with atopic dermatitis. The results show that many of the patients have IgE ab to these allergens in keeping with their skin tests. In all cases, the IgE ab was paralleled by IgG ab to the same allergen. In many sera, IgE ab to these inhalant allergens made a significant contribution to the total serum IgE. With two other allergens to which these patients had not been exposed, specific IgE ab was detected in only one serum, whereas the 42 sera tested did not contain IgE ab to diphtheria toxin. Eleven of the adult patients with atopic dermatitis had no history of asthma and had strongly positive skin tests. This group of patients had levels of total IgE and specific ab to antigen P₁ that were very similar to those found in a comparable group of patients who had both atopic dermatitis and asthma. Our recent finding that allergens applied to the skin can induce delayed eczematous lesions provides a mechanism by which allergens could contribute to skin lesions. Our present results support the view that specific sensitivity to common allergens should be taken into account in considering the causes of these patients' skin lesions.     

Elevated IgG immune complexes in children with atopic eczema

The levels of serum IgG complement-fixing immune complexes were studied in 20 children with atopic eczema and in 10 children with allergic rhinitis as control subjects with the use of a Raji cell assay. Immune-complex levels were strikingly elevated in those with eczema, 50 +/- 10 SE micrograms/ml, compared to control subjects 11 +/- 9 micrograms/ml (p less than 0.0047), the latter falling within the range for nonallergic subjects. Levels tended to be higher in those subjects with more severe eczema, but there was no statistically significant correlation, nor were levels correlated with serum IgE. Sucrose-density gradient analysis demonstrated the immune complexes to be present in two peaks, 8 to 10S and 21S or higher. High-molecular-weight IgG immune complexes that are complement-fixing may promote the characteristic pruritus of eczema by formation of anaphylactic complement fragments and the release of inflammatory substances from cutaneous mast cells, as well as contributing to the impaired cell-mediated immunity associated with the disease.     

Lymphocytes with receptors for IgG and IgM in atopic eczema and their relationship to serum IgE levels

Twenty patients with atopic eczema were compared with twenty non-atopic healthy controls. The atopic patients had significantly reduced percentages of lymphocytes bearing receptors for the Fc fragment of IgG (EAγ) in the peripheral blood. Percentages of lymphocytes with receptors for the Fc fragment of IgM (EAγ) did not differ significantly between the atopics and the controls. Serum IgE levels were significantly raised in the patient group and overall serum IgE levels were significantly inversely correlated with percentage EAγ. Although significant (P=0.007), this correlation was not strong (r=0.43) and the relevance of this to atopic disease is discussed.     

Total and specific IgG4 antibody levels in atopic eczema.

Total IgG4 and IgG4 antibody levels specific for 10 allergens (three inhaled and seven ingested) were measured by radioimmunoassay of sera taken from three groups of adult patients: (1) 32 cases of atopic eczema, (2) 28 cases of respiratory allergy and (3) 156 normal volunteers. In all three groups IgG4 antibody activity was mainly directed against common foods, and generally the group with atopic eczema had higher total and specific IgG4 levels than the cases of respiratory allergy, who in turn had higher titres than the normal group. There was within each group a tendency for men to have more total IgG4 than women and the difference was statistically significant among the normals. There was evidence of an IgG4 restricted response in atopic eczema because despite the group's elevated total IgG4 its total IgG4 remained within normal limits. Furthermore specific IgG4 was correlated with the corresponding specific IgE level in five of the 10 allergens examined. These results are generally consistent with the view that IgG4 levels are raised in cases of atopic eczema due to prolonged exposure to an allergen which initiated an IgE response.     

IgG autoantibody to IgE in atopic patients

An IgG type of antibody directed against IgE has been studied in serum from healthy and allergic individuals. The technique used is based on a solid phase paper radioimmunoassay in which the discs were sensitized with purified IgE myeloma. After incubation with patients' serum, human IgG labeled with iodine 125 was added. The anti-IgE antibodies were partially blocked by endogenous IgE in the serum and heating the serum samples at 56 degrees C disrupted the immune complexes (ie, IgG-aIgE:IgE), thereby increasing the detectable levels of IgG anti-IgE. The specificity of anti-IgE autoantibody was confirmed by both competitive inhibition and absorption experiments, using IgG, IgM, IgA, IgE, and rabbit anti-human IgG. Significantly raised levels of anti-IgE autoantibody were found in patients suffering from atopic disorders in comparison to the controls. These observations may suggest that the anti-IgE autoantibody could play a certain role in the modulation of IgE-mediated immune system and the pathogenesis of atopic diseases.     

Association of asthma with serum IgE levels and skin-test reactivity to allergens

We investigated the association of self-reported asthma or allergic rhinitis with serum IgE levels and skin-test reactivity to allergens in 2657 subjects in a general-population study. Regardless of the subjects' status with respect to atopy or their age group, the prevalence of asthma was closely related to the serum IgE level standardized for age and sex (P less than 0.0001), and no asthma was present in the 177 subjects with the lowest IgE levels for their age and sex (greater than 1.46 SD below the mean). The log odds ratio increased linearly with the serum IgE level after we controlled for possible confounders and the degree of reactivity to skin tests. In contrast, allergic rhinitis appeared to be associated primarily with skin-test reactions to common aeroallergens, independently of the serum IgE level. We conclude that asthma is almost always associated with some type of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of common aeroallergens we used to assess atopic status. These findings challenge the concept that there are basic differences between so-called allergic ("extrinsic") and nonallergic ("intrinsic") forms of asthma.     

The relevance of microbial allergens to the IgE antibody repertoire in atopic and nonatopic eczema

BACKGROUND: A propensity to microbial skin infections has been reported in atopic ("high IgE") and nonatopic ("low IgE") forms of eczema. However, the relationship between antimicrobial IgE antibodies and nonatopic disease is unclear. OBJECTIVE: We examined the relevance of microbial allergens to the allergen-specific IgE antibody repertoire in patients with atopic dermatitis. METHODS: Patients with IgE levels of less than 150 IU/mL were stratified according to sensitivity (n = 22) or no sensitivity (n = 27) to 11 common food allergens and aeroallergens. The prevalence and titers of antimicrobial IgE antibodies were compared with those of patients (n = 36) with increased total IgE levels (>150 IU/mL). Skin-derived serum chemokines were also analyzed. RESULTS: Patients with low IgE levels showed decreased disease severity, increased age of onset, a striking female predominance, and a distinct distribution of skin lesions. High titer IgE antibodies (sum of 8 bacterial and fungal allergens = 29.8 +/- 32.6 IU/mL) and multisensitization specific for microbial allergens was characteristic of patients with high IgE levels, with an overall 84% positivity; however, antimicrobial IgE antibodies comprised 3% or less of allergen-specific IgE antibodies. By contrast, antimicrobial IgE antibodies were detected in only 20% of patients with low IgE, and titers were negligible, irrespective of sensitization to common allergens. These patients were monosensitized, and exclusive microbial sensitivity was uncommon (10%). Patients with low IgE with no sensitivity to common allergens had lower levels of serum macrophage inflammatory protein 3alpha compared with their sensitized counterparts. CONCLUSION: Antimicrobial IgE antibodies are uncommon in patients with atopic dermatitis with low IgE levels. CLINICAL IMPLICATIONS: Hypersensitivity to microbial allergens is an unlikely trigger for eczematous eruptions in patients with low IgE levels.     

Analysis of IgE reactivities of purified allergens from Candida albicans and Malassezia furfur among patients with atopic dermatitis]

We analyzed the reactivities of a series of purified allergens from Candida albicans (C. albicans) and Malassezia furfur (M. furfur) with IgE antibodies in sera from patients with atopic dermatitis. We compared the specific IgE antibody levels to manganese superoxide dismutase (Mn SOD), cyclophilin, enolase, secretory aspartic protease (SAP 2) and type A mannan from C. albicans and Mn SOD, cyclophilin and Mal f 2 from M. furfur in 21 sera from patients with atopic dermatitis and 20 sera from patients with asthma without atopic dermatitis. The prevalence of IgE antibodies and the mean IgE antibody levels to all of the allergens tested were higher among patients with atopic dermatitis than among those with asthma without atopic dermatitis. More than 50% of patients with atopic dermatitis were IgE antibody-positive to Mn SOD, cyclophilin and type A mannan from C. albicans, and Mn SOD and cyclophilin from M. furfur. The availability of these purified allergens will facilitate studies on the contribution of fungal allergens to the development of atopic dermatitis.     

IgE and IgG4 subclass in atopic families

Raised levels of IgG4 were present in twelve (35%) of thirty-four asthmatic children and raised levels of IgE in twenty-three (68%). Eighteen of 104 first degree relatives also had raised levels of IgG4, thirteen had no history of atopic disease and nine failed to give positive skin reactions to Dermatophagoides pteronyssins or to mixed grass pollens. Fifteen relatives had raised IgE, five without symptoms. No relationship was noted between either raised levels of IgE or IgG4 and infant feeding. Although these immunoglobulin patterns were not consistently associated with symptoms they did tend to be associated in atopic families and it is suggested that the same polygenic factors may govern the IgE and IgG4 levels.     

IgE, IgG1, and IgG4 antibody responses to Blomia tropicalis in atopic patients

BACKGROUND: Allergens from house dust mites (HDMs), Dermatophagoides pteronyssinus and Blomia tropicalis are clinically relevant in atopic respiratory diseases in tropical countries. AIMS OF THE STUDY: To evaluate immunoglobulin (Ig)E, IgG1, and IgG4 antibody responses to B. tropicalis in Brazilian atopic patients. METHODS: About 110 patients with allergic rhinitis with/without asthma and 33 control subjects underwent skin prick testing (SPT) with HDM extracts, and their sera were tested for IgE and IgG subclass antibodies to D. pteronyssinus and B. tropicalis by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Most patients (56%) had positive SPT to B. tropicalis extract (B. tropicalis+ group), although 51% were reactive to both B. tropicalis and D. pteronyssinus and 6% were sensitized to B. tropicalis only. IgE-ELISA detected 43%B. tropicalis positivity with high-specific IgE levels in B. tropicalis+ patients. Specific IgG4 levels were higher in B. tropicalis+ than B. tropicalis- groups and correlated with specific IgE levels. The IgG1 levels to B. tropicalis were higher in patients than controls. The major allergenic B. tropicalis components recognized by B. tropicalis+ patient sera were the 54, 66, and 68 kDa proteins. The IgG4-binding protein profiles closely resembled that of IgE. The IgG1 antibodies recognizing multiple B. tropicalis protein species were detected in sera of all three patient groups. CONCLUSIONS: A large percentage of our allergic patients are B. tropicalis+. They are more frequently sensitized to high-molecular weight (HMW) B. tropicalis components than the major low-molecular weight (11-15 kDa) allergens detected in other studies. The results suggest that HMW B. tropicalis antigenic components are potential candidates for evaluating allergen exposure and sensitization, and for immunotherapy treatment.     

Specific IgE to food and inhalant allergens in intestinal washings of children affected by atopic eczema

Serum and rectal total and specific IgE were measured in eleven children with atopic dermatitis and eight with atopic dermatitis and associated wheezing. Specific IgE to food and inhalant allergens in rectal washings were found in fourteen patients. Of the seventy-six allergens which gave positive results, twenty were positive in both serum and intestine, thirty in serum alone and twenty-six in intestines alone. Specific intestinal IgE were confirmed by food challenge in three out of four patients whose skin-prick test and serum RAST were both negative. Local production of these antibodies was demonstrated by the ‘double ratio’ of Dcuschl and Johansson [1], and the ‘specific activity ratio’ of Platts-Mills [2]. Positive ratios (> 1) were obtained with both formulas for twelve of fourteen allergens tested. These data suggest that gut-associated lymphoid tissue may play a role in the pathogenesis of atopic disease.     

Higher pH level, corresponding to that on the skin of patients with atopic eczema, stimulates the release of Malassezia sympodialis allergens

BACKGROUND: The opportunistic yeast Malassezia is a trigger factor in atopic eczema (AE). Around 30-80% of patients with AE have an IgE and/or T-cell reactivity to the yeast. Several IgE-binding components have been identified in Malassezia extracts and 11 allergens have been cloned and sequenced. The pH of the skin surface in patients with AE is higher than that of normal healthy skin. We here investigate whether different pH conditions mimicking those of AE skin and healthy skin can influence the production and release of Malassezia allergens. METHODS: Malassezia sympodialis (ATCC strain 42132) was cultured in Dixon broth at pH 6.1 to 5.0 for 1-15 days. Culture supernatants were analysed for the presence of IgE-binding components by immunoblotting. The M. sympodialis cells were analysed for allergen expression and production with immunocytochemistry and quantitative polymerase chain reaction. RESULTS: We found that M. sympodialis cells produce, express and release allergens to a greater extent when cultured at the higher pH. This was particularly true of a 67-kDa major allergen designated Mala s 12. CONCLUSIONS: The data suggest that the skin barrier in AE patients provides an environment that can enhance the release of allergens from M. sympodialis, which can contribute to the inflammation.     

Elevated serum IgG4 levels in cystic fibrosis patients

The quantitative measurement of the IgG subclass composition of the sera from sixteen patients with cystic fibrosis has revealed grossly elevated levels of IgG4 in seven patients. The possible significance of this observation is discussed in relation to recent reports of a high incidence of immediate-type hypersensitivity in such patients.     

Specific IgE antibodies in atopic eczema

Radioallergosorbent tests (RAST'S) with 35 antigens and total serum IgE levels were performed on sera from 25 patients with atopic eczema, ranging from mild to very severe, who had been evaluated clinically and, when possible, skin-tested to inhalant allergens. IgE levels varied from 95 to 112,000 I.U., with a geometric mean of 2,200 I.U. Individual patients' sera gave an average of 8.4 positive RAST's to 14 inhalant allergens with a range of from 1 to 14 positive tests. The correlation of RAST with skin tests averaged 55 per cent with no difference observed with either the scratch or the prick methods. The degree of correlation was not related to severity of eczema. In eczema patients the great majority of noncorrelating tests were RAST positive and skin-test negative, unlike the noncorrelating tests found in children with asthma and allergic rhinitis, where there are more positive skin tests with negative RAST. The 25 sera were tested by RAST with 18 food antigens and the various sera gave from 1 to 18 positive tests, with an average of 9.7. IgE antibodies reacting with at least one of the DPT antigens were found in 10 of the 25 sera. Sera from 4 of the patients studied contained IgE antibodies that combined with all 35 antigens studied. Control RAST's with these sera were negative. This study shows that much of the elevation of serum IgE observed in atopic eczema represents specific IgE antibodies that can combine with common antigens with relatively high affinity.     

Egg white-specific IgE and IgG4 antibodies in atopic children

IgE, IgG1, and IgG4 antibodies in egg allergy were evaluated. It was found that there was a correlation between clinical egg sensitivity and IgE RAST from birth to 5 years of age, although IgG1 and IgG4 antibodies tended to increase with age in egg-allergic subjects. The role of IgG subclass antibodies in this allergic disorder is also discussed.