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.     

Interleukin-10 haplotype associated with total serum IgE in atopic dermatitis patients

BACKGROUND: The genetic background of atopic dermatitis (AD) is not clearly understood. Interleukin (IL)-10 is a powerful Th-2 cell cytokine produced by lymphoid cells that exerts its function by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines [IL-1, tumour necrosis factor-alpha (TNFA), IL-6, IL-8 and IL-12]. OBJECTIVE: In an effort to discover additional polymorphism(s) in genes whose variant(s) have been implicated in total immunoglobulin E (IgE) level in AD patients, we scrutinized the single nucleotide polymorphisms (SNPs) in the IL10 gene as a potent candidate for contributing to the level of IgE in serum. METHODS: We recruited 334 AD patients and assayed their serum total IgE levels using the LIPA-200 system. Four SNPs in the IL10 gene were genotyped using the single-base extension (SBE) method. Logistic regression analyses were performed with single polymorphisms and haplotypes (ht) to determine their association with the level of serum total IgE. RESULTS: Genetic association analysis of total serum IgE in AD patients revealed that one of the IL10 ht, IL10-ht2, was associated with decreased serum total IgE in gene dose-dependent manner (P = 0.02-0.001). CONCLUSIONS: It was predicted that the inhibition of innate immunity by increased IL-10 production in IL10-ht2-bearing individuals might be associated with decreased total serum IgE levels among AD patients. The greater effects of IL10 ht on decreased total serum IgE levels suggest that the effect of IL-10 polymorphism might be the result of a combined genotype (ht) rather than single polymorphisms.     

Expression of IL-18 mRNA and secretion of IL-18 are reduced in monocytes from patients with atopic dermatitis

BACKGROUND: Nasal polyps (NPs) are characterized by eosinophilic inflammation and often coexist with asthma. However, the role of atopy and IgE in NP pathogenesis is unclear. OBJECTIVE: We sought to determine whether there is an association between total and specific IgE to a variety of allergens in polyp and nonpolyp tissue and markers of eosinophilic inflammation or skin test results. METHODS: Homogenates were prepared from nasal tissue of 20 patients with NPs and 20 patients without NPs and analyzed for concentrations of IL-5, IL-4, eotaxin, leukotriene (LT) C4/D4/E4, sCD23, and histamine (ELISA). Eosinophil cationic protein (ECP), tryptase, and total and specific IgE for inhalant allergens and Staphylococcus aureus enterotoxins were measured (ImmunoCAP). RESULTS: The concentrations of total IgE, IL-5, eotaxin, ECP, LTC4/D4/E4, and sCD23 were significantly higher in NP tissue compared with nonpolyp tissue. Total IgE was significantly correlated to IL-5, ECP, LTC4/D4/E4, and sCD23 and to the number of eosinophils in NPs. On the basis of the presence of specific IgE antibodies in tissue, 3 NP groups were defined. NP group 1 demonstrated no measurable specific IgE, and NP group 2 selected specific IgE. The third group demonstrated a multiclonal specific IgE, including IgE to S aureus enterotoxins, a high total IgE level, and a high prevalence of asthma. CONCLUSIONS: These studies suggest that there is an association between increased levels of total IgE, specific IgE, and eosinophilic inflammation in NPs, which may be of relevance in the pathophysiology of nasal polyposis. Similarly, the presence of specific IgE to staphylococcal enterotoxins A and B also points to a possible role of bacterial superantigens.     

Increased serum nitrate levels in infants with atopic dermatitis

BACKGROUND: The pathogenesis of atopic dermatitis (AD) is still unknown. A recent study has shown that inducible nitric oxide synthase (iNOS) is expressed in the atopic skin lesion, suggesting the involvement of nitric oxide in the skin inflammation of AD. The purpose of the study was to examine serum nitrate (NO3) levels in relation to the disease severity in children with AD. METHODS: Serum nitrate levels were assessed in relation to the skin scores in 88 patients with atopic dermatitis (AD) (aged 0.4-8 years: mean+/-SD, 2.2+/-1.9, 41 boys and 47 girls) and 12 nonatopic children (aged 0.8-4 years: mean+/-SD, 1.8+/-0.9, seven boys and five girls). RESULTS: Serum nitrate levels of patients with AD were significantly increased as compared to nonatopic controls and were also correlated with the disease severity. The skin scores were significantly correlated with serum nitrate levels as well as peripheral eosinophil counts. CONCLUSION: Our results indicate that nitric oxide may be involved in the pathogenesis of vasodilation and erythema in AD skin.     

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.     

Prevalence of atopic dermatitis and serum IgE of Yusho patients born before 1967

Dioxins may have an impact on the human immunological system, which would increase the risk to develop allergic diseases, such as atopic dermatitis. In order to determine the lifetime prevalence of atopic dermatitis in Yusho patients, a questionnaire-based survey was conducted in 2008. One thousand and seventy-one out of 1430 certified yusho patients who were born before Yusho accident answered the questionnaires, and the prevalence of atopic dermatitis in Yusho patients was 5.5%. We also measured serum IgE in 515 Yusho patients who attended annual medical check-ups from 2007 to 2009 and in 172 control subjects. Serum levels of IgE in Yusho patients were 250.7 +/- 663.4 IU/ml, whereas those in control subjects were 265.0 +/- 602.0 IU/ml. There was no significant difference in serum levels of IgE between Yusho patients and control subjects. In addition, no significant correlation was observed between serum levels of IgE and blood levels of dioxins in Yusho patients.     

Role of IgE in atopic dermatitis

Atopic dermatitis is a chronic inflammatory skin disease associated with elevated serum IgE levels and sensitization to a variety of inhalant, food and microbial allergens. Controlled challenges have provided substantial evidence that allergens can trigger acute IgE-mediated mast-cell dependent exacerbations of eczema in these patients. However, the sustained chronic skin inflammation that characterizes atopic dermatitis is likely to result from a local expansion of allergen-specific T helper type 2 cells that produce interleukin-4 and interleukin-5 and the concomitant infiltration of eosinophils. An important role for IgE in allergen presentation to T helper type 2 cells by Langerhans cells has been proposed. These observations may have important implications for the development of new approaches for the treatment of this increasingly common allergic disorder.     

Increased plasma LIGHT levels in patients with atopic dermatitis

LIGHT [the name of which is derived from 'homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator (HVEM), and expressed by T lymphocytes'], is a member of the tumour necrosis factor superfamily that is involved in various inflammatory diseases. We aimed to estimate the relevance of plasma LIGHT levels as a biomarker for atopic dermatitis (AD). In order to understand the putative role of LIGHT in AD pathogenesis, we also investigate the effects of LIGHT on a monocytic cell line, human acute monocytic leukaemia cell line (THP-1). We examined plasma LIGHT levels, total serum IgE, serum value of CCL17 and peripheral blood eosinophil counts in patients with AD and healthy subjects. The effects of LIGHT on activation and apoptosis in THP-1 cells were also investigated. The plasma concentrations of LIGHT in AD patients were significantly higher than those in healthy individuals and the concentrations decreased as the symptoms were improved by treatment. The LIGHT plasma concentrations correlated with IgE levels and the Severity Scoring of AD (SCORAD) index. In addition, LIGHT stimulation increased expression of CD86 and induced production of interleukin-1β in THP-1 cells. Apoptosis was inhibited, the Bcl-2 level increased and the caspase-3 level decreased in THP-1 cells stimulated with LIGHT, compared to unstimulated control cells. These results suggest that plasma LIGHT levels may be one of the promising biomarkers for AD.     

Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD)

The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1–708 U/ml), compared with healthy non-atopic controls (P< 0.001), where the median level was 11 U/ml with a range of 1–1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.     

Essential fatty acids in serum lecithin of children with atopic dermatitis and in umbilical cord serum of infants with high or low IgE levels

The fatty acid composition of serum lecithin from children with atopic dermatitis (AD) was found to be abnormal, characterized by significantly increased proportion of linoleic acid and reduced levels of metabolites of this fatty acid. The levels of linoleic acid in umbilical cord serum lecithin were significantly higher in babies with high serum IgE than in those with low or non-demonstrable serum IgE. Since elevated cord serum IgE is strongly associated with development of atopic disease the results suggest that fatty acid changes may be a basic feature of AD. Immunologic dysfunction in patients with AD may possibly partly be a consequence of the fatty acid abnormality.     

Comparison of serum specific IgE antibodies to staphylococcal enterotoxins between atopic children with and without atopic dermatitis

BACKGROUND: The skin of patients with atopic dermatitis (AD) exhibits a striking susceptibility to colonization and infection by Staphylococcus aureus. The exotoxins secreted by S. aureus can act as superantigens and classic allergens, inducing the production of functionally relevant specific IgE antibodies. The aim of this study was to compare the levels and positive rates of serum staphylococcal enterotoxin A (SEA)- and staphylococcal enterotoxin B (SEB)-specific IgE between atopic children with and without AD. METHODS: Sixty children with AD, 55 children with respiratory allergy without AD, and 24 nonatopic healthy children were studied. The levels and positive rates of serum SEA- and SEB-specific IgE were compared among three groups. The correlation between the levels or positive rates of serum SEA/SEB-specific IgE and the severity of AD or the presence of previous skin infections was studied. RESULTS: The children with AD had significantly higher levels and positive rates of serum SEA- and SEB-specific IgE than the atopic children without AD (P < 0.001) and the nonatopic children (P < 0.001). There was no significant difference in the levels and positive rates of serum SEA- and SEB-specific IgE between the atopic children without AD and the nonatopic children. With or without adjustment for the potential confounding effect of total serum IgE levels, the levels and positive rates of serum SEA- and SEB-specific IgE were significantly correlated with severity of AD (P <0.005), but they were not significantly different between AD children with and without previous skin infections. CONCLUSIONS: SEA and SEB may contribute to chronic inflammation and exacerbation of AD through the IgE-mediated immune response.     

Cellular immunity and IgE levels in atopic patients

Twenty young adult atopic patients and their matched controls were studied. Spontaneously generated and Con-A-induced suppressor T cell functions as well as Natural Killer (NK) activity against K-562 target cells, measured in a short-time 3H-thymidine uptake, were evaluated. Suppressor T cell activity in the patients was more than 2 SD lower than that found in the controls and there was, contrary to expectation, a direct correlation between suppressor function and serum IgE levels. Atopic patients showed a statistically significant lower NK activity than normal controls when related to a low IL-2 production. Both facts inversely correlated with the concentration of IgE in serum. We concluded that atopic patients' vulnerability to viral infections may be due to defective NK activity. Suppressor T cell function is abnormal in these patients. Both defects could be due to a faulty immunoregulatory helper function.     

Some factors influencing the serum IgE levels in atopic diseases

Diagnosis of atopic diseases can sometimes present difficulties. IgE estimation in serum can obviously be of value in these cases. However, on evaluating the results consideration must be taken of several different factors which may be of importance with regard to the levels of this immunoglobulin. Some of these are discussed here. Patients with asthma and atopic eczema have raised IgE levels more often than patients with hay fever. In the latter cases a significant increase in the IgE level is found during the pollination season. Dust and mould seem to be weak allergens which seldom give rise to elevated IgE levels.

Specific hyposensitizaion significantly increased the IgE levels during the first 3 weeks of treatment. Steroids, cytostatics and disodium cromoglycate do not seem to influence the IgE concentrations nor do bacterial or viral infections. Markedly increased IgE concentrations were found in patients with parasitic infestations; Ascaris lumbricoides is one of the parasites of current interest.

     

In vitro responsiveness to IL-18 in combination with IL-12 or IL-2 by PBMC from patients with bronchial asthma and atopic dermatitis

Interleukin (IL)-18 is a proinflammatory cytokine and is now recognized as an important regulator of both helper T cells (Th) 1 and 2 cytokine production. An increased IL-18 secretion has been reported in patients with allergic disorders. It is predominantly produced by activated macrophages, and synergizes with IL-12 and IL-2 to induce IFN-gamma synthesis, thereby promoting Th1 cytokine response. Paradoxically, IL-18, by itself, strongly induces immunoglobulin (Ig) E and allergic inflammation, indicating a role for IL-18 in promoting Th2 response. We investigated the inducing effect in vitro of combining IL-18 and Il-12 or Il-2 on Th1- and Th2-type cytokines production by peripheral blood mononuclear cells (PBMC) from patients with allergic diseases. PBMC derived from 44 allergic patients [23 bronchial asthma (BA) and 21 atopic dermatitis (AD)] and 20 healthy controls were cultured with IL-18 in the presence of phytohemagglutinin (PHA) and IL-12 or IL-2. The levels of IFN-gamma, IL-13, and IL-4 in the culture supernatants were measured using enzymatic immunoassaying. IFN-gamma production was detected in all cultures from nonallergic controls stimulated with IL-18 in the presence of IL-12; however, the results for five BA patients and five AD patients were under the detection limit for IFN-gamma. In collaboration with IL-2, IL-18 was able to induce IFN-gamma production by PBMCs from all nonallergic controls and all allergic patients, with the exception of one AD patient. Synergistic induction of IL-13 production was found in cultures with IL-18 + IL-2, and the IL-13 induction was significantly increased in BA patients when compared with that in nonallergic controls (P = 0.006). The stimulation by IL-18, even in combination with IL-2, failed to induce IL-4 production by PBMC from both nonallergic controls and allergic patients. Although the induction of IFN-gamma by IL-18 + IL-12 was impaired in around a quarter of the allergic patients, the impairment of the IFN-gamma production was completely restored by IL-2 in the presence of IL-18. Thus, IL-18 enhances IFN-gamma production through an IL-12-dependent pathway and exhibits synergism when combined with IL-2 in terms of enhanced IL-13 and IFN-gamma production, suggesting the involvement of IL-18/IL-12/IL-2 pathway in modulating Th1/Th2 cytokine response.