Comparison of total IgE and anti-mite IgE antibody levels in the sera of patients with atopic dermatitis and/or atopic bronchial asthma

In the present study characterization of serological features of AD and/or BA patients were attempted. Nearly all of the patients (23 out of 24) with AD with or without episodes of BA had total IgE levels higher than 1,000 IU/ml. Conversely, 14 out of the 15 BA patients showed total IgE levels less than 1,000IU/ml.9 out of the 14 AD patients with BA(AD + BA) had histories of childhood asthma but required no current treatment for BA. The rest of the AD + BA patients required medication for BA but they were easily controllable with conventional bronchodilators such as beta 2 stimulators and/or xanthine derivatives. It was shown that AD patients (n = 6) with extremely high titers of anti-mite IgE antibodies (more than 110 PRU/ml up to 820 PRU/ml) remained free from BA episodes in the presence of hyper IgE immunoglobulinemia (1,818 IU/ml to 47,300 IU/ml). The results indicated that hyper IgE immunoglobulinemia in atopic patients might prevent the development of severe BA, but on the other hand, increase the possibility of developing AD.     

Plasma separation in patients with bronchial asthma, atopic dermatitis and hyperimmunoglobulinaemia E

The effect of intensive plasma separation performed eight times within 5 weeks in four patients with atopic dermatitis, bronchial asthma and hyperimmunoglobulinaemia E was followed as regards clinical symptoms and changes in the concentrations of serum (S) IgE, S IgG, S IgA, S IgM, plasma complement C3 split products, S transferrin, blood eosinophils, chemotaxis of neutrophil cells and histamine metabolites in urine in samples obtained consecutively during the period of observation. The occurrence of circulating immune complexes (IC) was analysed by a polyclonal rheumatoid factor (pRF) agglutination inhibition assay and an IgE IC specific technique. IgE IC were demonstrated in three of the patients prior to plasma separation, complexed IgE was 2-3% of the total concentration of S IgE. In one patient complexes were detected by the pRF agglutination inhibition assay, also. In the three patients with IgE IC, the complexes disappeared during treatment, but recurred in two of the patients shortly after the last plasma separation. Shortly after eight separations the S IgE was reduced in all patients to a mean level of 46% of the pre-exchange concentrations. During the following 3 weeks the relative increase of S IgE in three of the patients was similar to the values obtained for S IgG. Serum IgG was subnormal in all patients during the period of treatment. Increasing numbers of eosinophils were observed in three of the patients after the fifth separation procedure. The histamine metabolite 1,4-methylimidazoleacetic (1,4- MIAA ) in urine was increased in all patients, but no significant changes were observed during the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histological and immunological studies on eosinophilic granuloma of soft tissue, so-called Kimura's disease

Increase of serum IgE with frequent localization of IgE in the germinal centres, mast cell hyperplasia in lymph nodes and changes of specific granules in the infiltrated eosinophils, such as roughness of the matrix and appearance of tubular structures together with fusing and disappearance of the core, were demonstrated in eosinophilic granuloma of the soft tissue, so-called Kimura's disease, in association with increase of anti-Candida IgE antibody. It is suggested that this disease may be due to atopic allergy to Candida albicans.     

IgE Associated nephropathy in a patient with subcutaneous eosinophilic lymphoid granuloma (Kimura's disease)

Summary A patient with subcutaneous eosinophilic lymphoid granuloma (Kimura's disease) associated with a high serum IgE level and a marked blood eosinophilia, had a glomerulonephritis with electron dense deposits in mesangial, paramesangial, subendothelial, intramembranous and epimembranous areas. By immunofluorescence, all the glomeruli showed predominant depositions of IgE and IgG along the paramesangial areas and capillary walls together with complement components. The germinal centers in the lymph follicles formed in both the subcutaneous granuloma and the kidney interstitium also contained mainly IgE and IgG but no complement components. These features of this disease suggest that the glomerular lesion is one of the systemic manifestations of Kimura's disease.     

Respiratory symptoms, bronchial hyper-responsiveness, and eosinophilic airway inflammation in patients with moderate-to-severe atopic dermatitis

BACKGROUND: Patients with atopic dermatitis (AD) often have symptoms suggestive of asthma or rhinitis. The prevalence and signs of respiratory disease in AD patients have been studied to a limited extent. OBJECTIVES: To assess the prevalence and clustering of respiratory symptoms, bronchial hyper-responsiveness (BHR), and eosinophilic airway inflammation in patients with moderate-to-severe AD. METHODS: Eighty-six consecutive patients with moderate-to-severe AD and 49 randomly selected control subjects without AD were studied by questionnaire, flow volume spirometry, histamine challenge to detect BHR, induced sputum test to detect eosinophilic airway inflammation, and skin prick tests (SPTs) and total serum immunoglobulin (Ig)E measurements to detect atopy. RESULTS: The patients with AD showed increased risk of physician-diagnosed asthma (36% vs. 2%, odds ratio (OR) 10.1, confidence interval (CI) 1.3-79.7, P=0.03), physician-diagnosed allergic rhinitis (AR) (45% vs. 6%, OR 4.5, CI 1.2-16.7, P=0.02), BHR (51% vs. 10%, OR 5.5, CI 1.5-20.1, P=0.01), and sputum eosinophilia (81% vs. 11%, OR 76.1, CI 9.3-623.5, P<0.0001) compared with the control subjects. In AD patients, elevated s-IgE and positive SPTs were associated with the occurrence of physician-diagnosed asthma and AR, BHR, and the presence of sputum eosinophilia. CONCLUSIONS: BHR and eosinophilic airway inflammation are more common in patients with AD than in control subjects. The highest prevalences were seen in patients with AD who were SPT positive and had high IgE levels. Longitudinal studies are needed to assess the outcome of patients with signs of airway disease, in order to identify those who need early initiation of asthma treatment.     

IgE antibodies to Mycoplasma pneumoniae in asthma and other atopic diseases

IgE antibodies to Mycoplasma pneumoniae antigens were measured by RAST assay in 152 patients with asthma and other IgE and non-IgE mediated diseases. Five patients with asthma and/or atopic dermatitis had highly elevated Mycoplasma RAST binding ratios, p < 0.001. For these five patients the ratios ranged from 1.78 to 4.74. These increased ratios persisted at least two to 16 months in three of four individuals who were evaluated sequentially. RAST inhibition studies using Mycoplasma pneumoniae, Mycoplasma control, Streptococcus MG and viral antigens showed the specificity of binding for M. pneumoniae in these five patients indicating the presence of IgE antibodies to M. pneumoniae.     

Deficient Concanavalin-A-induced suppressor-cell activity in patients with bronchial asthma, allergic rhinitis and atopic dermatitis

Concanavalin-A (Con-A)-induced suppressor activity against the proliferative response of autologous lymphocytes to phytohaemagglutinin (PHA) was examined in the peripheral-blood lymphocytes from fourteen patients with bronchial asthma, ten patients with allergic rhinitis and eleven patients with atopic dermatitis and compared with eleven simultaneously studied healthy normals. Eight of fourteen patients (57%) with bronchial asthma, eight of ten patients (80%) with allergic rhinitis and five of eleven patients (45%) with atopic dermatitis demonstrated deficient Con-A-induced suppressor function. Abnormal suppressor-cell functions could play an important role in the pathogenesis of atopic states.     

Serum macrophage-derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, macrophage-derived chemokine (MDC)/CCL22, a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)-expressing cells, in addition to thymus and activation-regulated chemokine (TARC). We have previously reported that serum TARC levels correlate with the severity of AD. In this report, we investigated the participation of MDC in AD. First, we measured serum MDC levels in 45 patients with AD, 25 patients with psoriasis vulgaris and 25 healthy controls. Serum MDC levels in AD patients were significantly higher than those in healthy controls and psoriasis patients. Furthermore, the increases in serum MDC levels in AD patients were greater in the severely affected group than in the moderate or mild groups. We compared serum MDC levels in 11 AD patients, before and after treatment, and observed a significant decrease after treatment. Moreover, the serum MDC levels significantly correlated with the Scoring AD (SCORAD) index, serum soluble (s) E-selectin levels, serum soluble interleukin-2 receptor (sIL-2R) levels, serum TARC levels and eosinophil numbers in peripheral blood. Our study strongly suggests that serum MDC levels have a notable correlation with disease activity and that MDC, as well as the CC chemokine TARC, may be involved in the pathogenesis of AD.     

Serum IgE concentration in atopic dermatitis. Relationship to severity of disease and presence of atopic respiratory disease

A survey was conducted to evaluate the serum IgE concentrations of 58 patients with atopic dermatitis of varying severity and activity. The determination of serum IgE concentrations does not provide a diagnostic criterion for atopic dermatitis because 57% of the patients had levels of IgE considered to be within a normal range. When serum IgE concentrations are elevated in atopic dermatitis, this is associated with an increased severity of the disease, with coexistent atopic respiratory disease or with both. This association may have relevance to the pathogenesis of the respiratory disease, which is IgE-mediated, the severity of the dermatitis, or both. The manner in which this may occur, if there is more than a coincidental relationship, is uncertain.     

Serum IgE levels in patients with inflammatory bowel disease

The role of allergy in the pathogenesis of inflammatory bowel disease (IBD) is unclear. The present study was performed to evaluate serum levels of IgE and other immunoglobulin classes in patients with IBD. Patients with IBD had significantly elevated serum levels of both IgG and IgM in the presence of normal levels of IgA. Serum concentration of IgE, as well as the prevalence of patients with "high IgE" were significantly increased in IBD. Among patients with IBD, those with Crohn's disease or those in relapse had the highest levels of IgE. The possibility that allergy plays a pathogenic role in a subset of IBD is discussed.     

An electron spin resonance (ESR) study of lymphocyte membrane fluidity in patients with bronchial asthma and atopic dermatitis]

The lymphocyte membrane fluidity of patients with allergic diseases was measured by electron spin resonance (ESR), and the effect of the epinephrine stimulation on the membrane fluidity was examined. The peripheral lymphocytes were obtained from 15 patients with bronchial asthma and atopic dermatitis (28.7 +/- 9.9 years old, 10 females and 5 males) and 11 healthy adults (30.5 +/- 4.6 years old, 2 females and 9 males). Lymphocyte membranes were spin-labeled with 5-doxyl-stearic acid. Before and after the stimulation of epinephrine of the final concentrations at 10(-5) and 10(-4) mol/l, ESR spectra of the outer membranes were analyzed to evaluate the membrane fluidity. The membrane fluidity of the intact lymphocytes of allergic patients was significantly decreased in comparison to healthy controls. Although the epinephrine stimulation increased the lymphocyte membrane fluidity, the increase in fluidity was less in allergic patients than in healthy controls. There are various receptors on the surface of the lymphocyte membranes, and changes of the membrane fluidity have an influence on their functions. The results in this study elucidate the decreased fluidity of lymphocyte membrane in patients with bronchial asthma and atopic dermatitis, and suggest that the functions of the membrane receptors might be impaired.     

Differences in cytokine production by peripheral blood mononuclear cells (PBMC) between patients with atopic dermatitis and bronchial asthma.

It is widely accepted that type 2 helper T (Th2) lymphocytes play a crucial role in the pathogenesis of atopic dermatitis (AD) as well as bronchial asthma (BA). We measured the amounts of IL-5 and interferon-gamma (IFN-gamma) produced by PBMC upon stimulation with house dust mite (HDM) or Candida albicans (CA) in 17 children (3-15 years) with AD, and compared these values with those of 16 children with BA. Although IL-5 production by PBMC upon stimulation with HDM in patients with AD was significantly higher than that in 13 non-atopic controls (geometric mean = 23.4 pg/ml versus 5.9 pg/ml, P < 0.05), it was significantly lower than that in patients with BA (177.8 pg/ml, P < 0.001). The amount of IL-5 produced by PBMC upon stimulation with CA was also significantly lower in patients with AD than in those with BA (7.2 pg/ml versus 100.0 pg/ml, P < 0.001). The production of IFN-gamma by PBMC stimulated with HDM or CA was also significantly lower in patients with AD than in those with BA (HDM 4. 3 pg/ml versus 12.6 pg/ml, P < 0.05; CA 6.5 pg/ml versus 60.3 pg/ml, P < 0.001). Consequently the ratio of IL-5 to IFN-gamma production was high not only in patients with BA but also in those with AD. These findings suggest that there are some differences in the regulation of in vivo cytokine production between patients with AD and those with BA, although a Th2-dominant profile is common to both.     

Trimodality of serum Dermatophagoides farinae-specific IgE RAST levels in atopic dermatitis patients.

Serum Dermatophagoides farinae-specific IgE RAST (DF IgE) levels were assayed in 122 atopic dermatitis patients at the first examination. From the statistical study, we found trimodality of the individual variability of serum DF IgE levels. We hypothesize that serum DF IgE levels may be controlled by a pair of allelic genes.     

Prevalence and severity of allergic rhinitis in house dust mite-allergic patients with bronchial asthma or atopic dermatitis

BACKGROUND: Allergic rhinitis, asthma and atopic dermatitis are closely associated. Although population-based studies report a high prevalence of rhinitis among asthma patients, less is known of the association between rhinitis and atopic dermatitis and the severity of concomitant rhinitis. OBJECTIVES: We aimed to determine the prevalence and severity of allergic rhinitis among asthmatics and patients with atopic dermatitis and assessed whether age and comorbidity influence the severity of rhinitis signs and symptoms. METHODS: Three hundred and twenty-five patients recruited for a multicentre trial to study the effect of encasings of mattresses, pillows and duvets on signs and symptoms of allergic rhinitis and/or asthma and/or atopic dermatitis recorded visual analogue scores (VAS) and daily symptom scores and underwent nasal challenge tests with house dust mite (HDM). RESULTS: Based on history and clinical symptoms 92% of the 164 asthmatic patients and 85% of the 86 patients with atopic dermatitis could be diagnosed as having rhinitis. Inclusion of a positive provocation to HDM did not result in a substantial lower prevalence of rhinitis. Subjects reported moderate symptoms, with mean rhinitis VAS scores ranging from 40.0 to 55.0. Presence of atopic dermatitis was associated with lower rhinitis VAS and symptoms scores, whereas in multivariate analysis the presence of asthma was positively associated with nasal responsiveness to HDM. CONCLUSION: The prevalence of nasal symptoms in patients with bronchial asthma or atopic dermatitis and sensitized to house dust mites is high. Although the majority of patients experience mild to moderate symptoms, the presence of nasal disease needs to be examined in all patients with atopic disorders.     

Serum levels of IgG subclasses in relation to IgE and atopic disease in early infancy

The levels of IgG1, IgG2, IgG3, and IgG4 were analysed by ELISA in cord serum and in serum samples collected at 6 and 18 months of age from infants whose mothers were atopic. None of the four IgG subclasses was significantly influenced on any sampling occasion by infant atopy, gender, month of birth, maternal IgE or maternal diet during pregnancy and early lactation. However, at 18 months of age, significantly higher levels of IgG1 (P less than 0.05) and of IgG4 (P less than 0.01) were found in infants with an elevated IgE (greater than or equal to 8.0 kU/l) than in those with a lower level. A weak positive correlation (rs = 0.26; P = 0.05) between IgE and IgG4 was also observed. Despite the fact that the serum levels of IgG4 at 18 months were significantly higher (P less than 0.01) among infants with positive IgE-RAST (greater than or equal to 0.15 PRU/ml) to ovomucoid or beta-lactoglobulin, our data suggest that the the concentration of IgG4 relates more to the level of IgE than to the clinical symptoms of atopy. Determination of IgG subclasses seems to be of limited value for prediciting atopy during early infancy.     

High serum levels of additional IL-18 forms may be reciprocally correlated with IgE levels in patients with atopic dermatitis

We established an ELISA system for determination of as yet unidentified species of interleukin 18 (IL-18), named IL-18 type 2, in human serum. Serum IL-18 levels and their effect on IgE levels were examined in 18 patients with atopic dermatitis (AD) with no other allergic symptoms. Three of these patients showed high IL-18 type 2 concentrations (25-100 ng/ml) in their blood serum, and this IL-18 type 2 was detectable only with our established ELISA system. In contrast, the level of the conventional form of IL-18 (type 1) was found to be 50-400 pg/ml in all patients by the commercially available ELISA. The levels of type 1 IL-18 showed no correlation with those of type 2 and approximately 2-fold higher in AD patients than in normal subjects. IL-12 p40 and IgE levels were correlated in the patients with no IL-18 type 2, and interestingly, relatively low IgE concentrations were detected in the three IL-18 type 2-positive patients. They showed considerable levels of IL-12 p40 unlike normal subjects. The IFNgamma-inducing activity of IL-18 type 2 was >100-fold less potent by weight ratio than that of a recombinant 'active' IL-18 preparation, even after the treatment with Caspase 1. Although the relationship between AD and serum IgE levels is not clear cut, IL-18 type 2 appears to play some roles in the Th2-polarization involving IgE production in association with immune responses occurring in local inflammatory milieu such as atopic lesions.     

Decreased levels of coenzyme Q(10) in patients with bronchial asthma

BACKGROUND: The contribution of free oxygen radicals in the pathogenesis of bronchial asthma is generally accepted. The modulation of antioxidative defence by supplementation with antioxidants represents additive therapy in complex management of disease. The aim of the study was to assess the levels of coenzyme Q10, alpha-tocopherol, and beta-carotene both in plasma and whole blood, and malondialdehyde (MDA) and eosinophil cationic protein (ECP) in plasma of asthmatics (As). METHODS: Fifty-six As (15 males and 41 females) aged from 19 to 72 years (mean age 46 years) suffering from allergic asthma were enrolled into the study. The control group comprised 25 healthy volunteers (16 males, 9 females) aged 25-50 years. RESULTS: The concentrations of CoQ10 decreased significantly both in plasma and whole blood, compared with healthy volunteers (0.34 +/- 0.15 micromol/l vs. 0.52 +/- 0.15 micromol/l, 0.33 +/- 0.14 micromol/l vs. 0.50 +/- 0.13 micromol/l, P < 0.001, P< 0.001, respectively). The levels of alpha-tocopherol were decreased both in plasma and whole blood in comparison with controls [24.10 micromol/l (19.8; 30.5), vs. 33.20 micromol/l (28.25; 38.05), 17.22 +/- 6.45 micromol/l vs. 21.58 +/- 7.92 micromol/l, P= 0.006, P = 0.01, respectively]. The levels of MDA were elevated over the reference range in both groups (reference range < 4.5 micromol/l). No changes were seen in beta-carotene concentrations. Positive correlation was found between whole blood CoQ10 and alpha-tocopherol concentrations. CONCLUSION: Results of the study suggest a possible contribution of suboptimal concentrations of CoQ10 on antioxidative dysbalance in As and provide a rationale for its supplementation.