IgG4 antibodies in patients with atopic dermatitis

The role of IgG4 in atopic dermatitis was investigated by determining the total amounts of IgG4 and of IgG4 specific for ovalbumin (a food allergen), Dermatophagoides farinae mite antigen and house dust (inhalant allergens) and Candida. These were related to the amounts of total and antigen specific IgE in patients with atopic dermatitis and normal healthy controls. Most patients with atopic dermatitis had greater amounts of total IgG4 and of antigen-specific IgG4 than did normal control individuals. Patients who had received hyposensitization treatment injections had greater amounts of IgG4 than the atopic dermatitis patients not so treated. In patients treated by hyposensitization there was a large increase in the amount of blocking antibody detected by incubating the antigen with the serum overnight before injecting the mixture into the skin of a patient sensitive to the antigen. Blocking activity was also examined by partial inhibition by the serum of IgE-mediated mast cell degranulation and by injection of serum into the skin of sensitive patients before challenge with antigens. In all tests the blocking activity of the serum was related to the amount of antigen-specific IgG4 but not related to total IgG4. In patients with atopic dermatitis who were sensitive to mite antigen, severe cases had small amounts of specific IgG4 and large amounts of specific IgE but in mild cases there was an opposite trend with relatively large amounts of specific IgG4. Large amounts of IgG4 ovalbumin specific antibody were found in children and adults with atopic dermatitis and egg allergy but small amounts of IgE. In infants most of the anti-ovalbumin antibody was IgE with little or no IgG4. The work of others has confirmed that increased amounts of total and antigen-specific IgG4 occur in atopic dermatitis, and it is concluded that IgG4 is a blocking antibody for anaphylactic sensitization responses.     

Elevated serum IgE and IgG4 in patients with atopic dermatitis

The quantitative measurement of the IgE and IgG subclass levels in the sera of 29 patients with atopic dermatitis has revealed significantly elevated levels of IgE and IgG₄ in a relatively high proportion of patients with this condition compared to non-atopic patients with warts and to a group of normal volunteers studied previously. The possible significance of these observations is discussed in relation to current evidence suggesting the involvement of IgG4 in certain immediate-type hypersensitivity disorders.     

Urinary leukotriene E4 levels in patients with atopic dermatitis

Leukotriene synthesis may be increased in a variety of inflammatory diseases. Urinary leukotriene E₄ is a stable metabolite of leukotrienes C₄ and D₄ which has previously been found to be increased in exacerbations of severe asthma and after antigen inhalation. Levels of urinary LTE₄ in seven patients during and after a severe flare of atopic dermatitis were measured by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Mean urinary LTE₄ levels (± SEM) were not increased during (16·7 ± 3·7pg/μmol) or after (16·9 ± 4·8 pg/μxmol) the acute exacerbation of atopic dermatitis when compared with the normal range (mean = 23·8 [95% confidence interval 19·9–28·2] pg/μmol creatinine). These findings do not provide evidence of cysteinyl leukotriene involvement in the pathogenesis of atopic dermatitis.     

IgE antibodies to Pityrosporum ovale in atopic dermatitis

An enzyme-linked immunosorbent assay (ELISA) was developed to assess serum IgE antibodies directed against Pityrosporum ovale in patients with atopic dermatitis (AD), atopic patients with allergic respiratory disease (ARD: rhinitis or asthma) but without eczema, and in healthy controls. IgE binding to P. ovale extract was demonstrated in 49% (35/72) of AD patients. In contrast, anti-P. ovale IgE was found in only one of 27 atopic controls without eczema; all healthy control sera (n = 17) were negative. Of 37 AD patients tested intracutaneously with P. ovale, 31 showed immediate-type reactivity, and 20 of these 31 patients had anti-P. ovale IgE detectable by ELISA, while sera from the six non-responders were all negative. Levels of anti-P. ovale IgE were highest in AD patients aged 20-30 years. No correlation was found with the severity of AD, but there was a non-significant tendency (P = 0.06) to higher levels in AD patients with concomittant respiratory allergy. Anti-P. ovale IgE was significantly correlated with total serum IgE, with specific IgE against various aeroallergens as measured by RAST, and with levels of anti-Candida albicans IgE, measured with a similar ELISA. Thus, production of IgE antibodies against P. ovale occurs very frequently in AD, and rarely in patients with atopic disease without skin involvement.     

THE CLINICAL RELEVANCE OF HEAT-STABLE, SHORT-TERM SENSITIZING ANAPHYLACTIC IgG ANTIBODIES (IgG S-TS) AND OF RELATED ACTIVITIES OF IgG4 AND IgG2

book reviewed in this article: Hormone Therapy of Acne. Clinical and Experimental Principles. Doris Fanta (1980) Manual of Skin Diseases. Gordon C. Sauer (1980) Entomology in Human and Animal Health. 7th edn. R.F.Harwood AND M.T.James (1979) Paraneoplasia: Biological Signals in the Diagnosis of Cancer. Jan G.Waldenströ (1978) Diseases of the External Ear. An Otologic-Dermatologic Manual. B.H.Senturia , M.D.Marcus AND F.E.Lucante (1980) Basic and Diagnostic Aspects of Cutaneous T Cell Lymphomas. E.M. VAN DER Loo (1980) Cytodiagnosis in Dermatology. V.Ruocco (1980) Photochemotherapy. Information for Doctors and Patients. Gerhard Weber (1980)     

Head and neck atopic dermatitis and malassezia-furfur-specific IgE antibodies

BACKGROUND: Atopic dermatitis of the head and neck (HNAD) has been recognized as a separate entity. Malassezia furfur, a lipophilic yeast, is considered to be a pathogenic allergen in this form of atopic dermatitis. OBJECTIVE: The purpose of this study was to determine the level of IgE anti-M.-furfur antibodies and their relation to the severity of the disease. METHODS: IgE anti-M.-furfur antibodies were assayed in 106 patients with HNAD. Controls included 25 patients with non-HNAD, 20 with nonatopic dermatitis and 16 with seborrheic dermatitis (including 4 with AIDS). RESULTS: There was a highly significant correlation between the level of anti-M.-furfur IgE and clinical severity. Furthermore, there was a significant but smaller correlation between total IgE and clinical severity. In patients with HNAD, total IgE was higher amongst men. CONCLUSION: IgE anti-M.-furfur antibodies are a good and specific marker for HNAD. IgE M. furfur levels are strongly correlated with the severity of the disease.     

In vivo formation of prostaglandin E1 and prostaglandin E2in atopic dermatitis

Immunological and biochemical alterations in atopic dermatitis have been attributed to a deficient conversion of omega-6 fatty acids (i.e. linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid) to prostaglandin (PG)E₁. In patients with atopic dermatitis, however, the formation of PGE₁ has not been evaluated so far. We therefore measured plasma concentrations of 15-keto-13.14-dihydro-PGE₁ which reflects endogenous PGE₁ release, by gas chromatography-mass spectrometry in 31 patients with atopic dermatitis (aged 18-41 years, median 26 years) and in 31 healthy, age and sex-matched control subjects. In order to exclude a metabolic shift from PGE₁ to PGE₂, we also measured the plasma levels of 15-keto-13, 14-dihydro-PGE₂. There was no difference between patients and control subjects with respect to plasma concentrations of 15-keto-13, 14-dihydro. PGE₁ (3.9-49.6, median 10.3pg/ml vs. 3.2-80.4, median 8.3pg/ml, P = 0.22), 15-keto-13,14-dihydro-PGE₂ (11.6-201.0 median 24.8pg/ml vs. 8.6-201.0.median 19.6 pg/ml, P = 0.10), and the ratio of 15-keto-13,14-dihydro-PGE₁ to 15-keto-13.14-dihydro-PGE₂ (0.17-1.39, median 0.41 vs.0.2-0.17, median 0.45, P = 0.29). These results indicate that the endogenous formation of both PGE₁ and PGE₂ is normal in our patients. The results do not confirm the pivotal role that other authors have attributed to a deficient PGE₁ formation in the pathogenesis of atopic dermatitis.     

Specific IgE antibodies to Pityrosporum orbiculare in patients with atopic dermatitis

By means of RAST investigations, we detected specific IgE antibodies against Pityrosporon orbiculare in the plasma of patients with atopic dermatitis. The patients suffering from the so-called head and neck dermatitis showed an average specific IgE antibody titer of RAST class 3, whereas in those with predominant involvement of the extremities we found an average antibody titer of RAST class 1.     

IgE and IgG4 levels in children with atopic dermatitis

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.     

Leukotrienes B4, C4 and D4 stimulate DNA synthesis in cultured human epidermal keratinocytes

Leukotrienes in psoriatic skin lesions are potent mediators of inflammation. We have studied the capacity of leukotrienes to stimulate the DNA synthesis of cultured human epidermal keratinocytes. At concentrations ranging from 10(-12) to 10(-8) M, LTB4 produced a 100% increase of DNA synthesis determined both as the incorporation of [3H] thymidine and as the labelling index. In comparison, LTB4 had no effect on the DNA synthesis of dermal fibroblast cultures. 5S,12S-LTB4 and 5S,12S-all-trans-LTB4 did not change the DNA synthesis of keratinocytes, but the effect of LTB4 was abolished in the presence of 5S,12S-all-trans HLTB4. Being less potent than LTB4 the peptidoleukotrienes (LTC4, LTD4) also stimulated keratinocyte DNA synthesis. The effect of the peptidoleukotrienes, but not of LTB4, was antagonized by FPL 55712. These results show that leukotrienes B4, C4 and D4 exert potent and stereospecific mitogenic effects on cultured human keratinocytes. The presence of these arachidonic acid metabolites in psoriatic skin lesions may be pertinent to both inflammation and aberrant epidermal growth in psoriasis.     

IgE antibodies to Staphylococcus aureus. Prevalence in patients with atopic dermatitis

We determined the prevalence of IgE antibodies to Staphylococcus aureus by optimized immunoradiometric assay methods in serum specimens from 69 patients with atopic dermatitis. All patients had positive aerobic cultures for S aureus from skin. Significant binding attributable to IgE antibodies was noted in three of 25 patients with atopic dermatitis and superimposed impetiginization or pustules, but antibodies were not detected in the remaining 44 patients whose lesions were colonized with S aureus. By comparison, IgE antibodies to S aureus were uniformly present in high titer in serum samples from patients with the hyperimmunoglobulin E syndrome. We conclude that most patients with atopic dermatitis do not have detectable levels of IgE antibodies to S aureus.     

Selective activation of circulating CD4+ lymphocytes in severe adult atopic dermatitis

An analysis of peripheral blood lymphocyte subsets and their expression of activation markers was performed using flow cytometry in 12 adult patients with severe atopic dermatitis, and compared with 14 normal individuals. Repeated measurements were made over an 8-week period during which disease activity was also assessed. Increased percentages of activated and unactivated CD4+ lymphocytes, and decreased percentages of CD8+ cells were observed in atopic dermatitis. Increasing disease activity was associated with an increase in the proportion of activated and unactivated CD4+ lymphocytes and a fall in the proportion of CD8+ cells. This study demonstrates that in adults with severe atopic dermatitis, increasing disease activity is associated with selective activation of CD4+ lymphocytes and a relative expansion of the CD4+ cell subset.     

Allergen-sensitive atopic dermatitis is improved by injections of allergen combined with F(ab')2 fragments of specific antibodies

Summary Symptoms of atopic dermatitis (AD) can be provoked by exposure to airborne allergens. We have previously shown that patients hypersensitive to D. pteronyssinus (Dpt) allergens were improved by administration of complexes composed of specific antibodies and allergen, which reduce the allergen-specific immune response. We now report that similar results can be achieved by using F(ab')₂ fragments of specific antibodies instead of whole antibody molecules. Eight adult patients with severe AD were included in a single-blind study. During the first 11 months patients were maintained on injections of carrier buffer alone, in an effort to evaluate the extent of spontaneous improvement. They were then treated with intradermal injections of allergen-F(ab')₂ complexes made from autologous specific antibodies and Dpt allergens. The majority of the patients improved spontaneously during the summer months, with an average 30% reduction of symptoms. However, a much more pronounced improvement was observed after 3 months on active therapy, corresponding to a cumulative amount of 60 μg F(ab')₂ and 15 μg allergens. The patients continued to improve over the next 5 months, showing an average 83% reduction of severity scores. The use of F(ab')₂ antibody fragments reduces the risk of inducing an anti-allotypic immune response, and raises the possibility of adding adjuvants to allergen-antibody complexes and/or using specific antibodies isolated from pooled gammaglobulins.