The relationship between serum levels of total IgE, IL-18, IL-12, IFN-gamma and disease severity in children with atopic dermatitis

Studies about the role of cytokines on the immunopathogenesis of atopic dermatitis (AD) are generally based on in vitro observations and this role has not been completely clarified yet. Serum levels of total IgE, IL-18, IL-12, IFN-gamma and the relationship between these parameters and disease severity, determined using the SCORAD index, in a group of atopic patients were investigated in this study. Serum levels of total IgE were measured by the nephelometric method and serum levels of IL-18, IL-12/p40 and IFN-gamma were measured by ELISA method. Serum levels of total IgE and IL-18 were found significantly higher in study group than in controls (P<.001). There was no statistically significant difference between patients and controls in respect of serum levels of IL-12/p40 (P = .227). A statistically significant relationship between SCORAD values and serum levels of total IgE (P < .001), IL-18 (P < .001), and IL-12/p40 (P < .001) was determined. These results show that serum levels of IL-18 can be a sensitive parameter that importantly correlates with clinical severity of AD, can play a role in the immunopathogenesis of AD, and furthermore may be used in the diagnosis and follow-up of the disease in addition to other parameters.     

The lumbar bone mineral density is affected by long-term poor metabolic control in adolescents with type 1 diabetes mellitus

AIM: To analyze whether bone mineral density (BMD) and bone resorption status are influenced by long-term metabolic control and duration of disease in adolescents with long-standing type 1 diabetes mellitus. METHODS: Twenty-seven adolescents (age 13.1 +/- 1.7 years, duration of diabetes 6.9 +/- 3.0 years) were studied. The BMD, expressed as z score, was measured at the lumbar spine (L1-L4) using dual-energy X-ray absorptiometry, while the urinary excretion of total deoxypiridinoline (Dpyd), a marker of bone resorption, was measured by immunoassay and was corrected by creatinine (Cr). Linear and multivariate correlations between lumbar BMD z score or Dpyd/Cr excretion and age and disease variables [short-term (Hb A(1c latest)) or long-term (Hb A(1c whole duration)) metabolic control, duration, 'diabetes impact index' (mean Hb A(1c whole duration) x duration of disease in months)] were sought. RESULTS: In diabetic subjects the mean BMD z score was -0.44 +/- (SD) 1.02 (95% CI: -0.03; -0.84), and the Dpyd/Cr excretion was not increased. A negative correlation was found between lumbar BMD z score and age (r -0.59; p = 0.001), duration (r -0.39; p = 0.04), and the diabetes impact index (r -0.4; p = 0.04). The Dpyd/Cr ratio correlated negatively with age (r -0.40; p = 0.04) and positively with height velocity (r 0.42; p = 0.04). By using multiple linear regression, age showed a significant inverse correlation with lumbar BMD z score (beta = -0.39; p = 0.0005). A negative correlation was found between lumbar BMD z score and Hb A(1c whole duration) (beta = -0.40; p = 0.02) or diabetes impact index (beta = -0.001; p = 0.01). CONCLUSIONS: Poor metabolic control may expose adolescents with long-standing type 1 diabetes to the risk of developing osteopenia in adult age. Optimization of metabolic control in growing diabetic children may prevent osteoporosis in later life.     

Early-Onset Atopic Dermatitis in Children: Which Are the Phenotypes at Risk of Asthma? Results from the ORCA Cohort

Background

Atopic dermatitis (AD) is known to predate asthma and other atopic disorders described under the term “atopic march”. However, this classic sequence is not always present and only a few studies have addressed children at risk of developing asthma. The objective of this study is to define early-onset AD phenotypes leading to asthma.

Methods

We performed a cluster analysis with 9 variables of 214 infants with early-onset AD prospectively enrolled in the ORCA cohort and followed each year on the occurrence of asthma until the age of 6.

Results

We identified 3 clusters - cluster 1 (n = 94) with low to no sensitization to food (27.7%) or aeroallergens (10.6%) and moderate AD severity (SCORAD 25.29 +/- 14.6) called “AD with low sensitization”; - cluster 2 (n = 84) characterized by a higher AD severity (SCORAD 32.66+/-16.6) and frequent sensitization to food (98.9%) or aeroallergens (26.2%), most likely multiple (96.4% for food allergens), called “AD with multiple sensitizations” - cluster 3 (n = 36) with parental history, moderate AD severity (SCORAD 24.46+/-15.7), moderate rate of sensitization to food allergens (38.9%) (exclusively single) with no sensitization to aeroallergens, called “AD with familial history of asthma”. Percentages of children suffering from asthma at the age of 6 were higher in clusters 2 and 3 (36.1% and 33.3% respectively versus 14.9% in cluster 1, p<0.01).

Conclusion

Two phenotypes in infants with early-onset AD convey a higher risk of developing asthma during childhood: multiple sensitization and familial history of asthma.     

Classification of established atopic dermatitis in children with the in vivo imaging methods

Atopic dermatitis (AD) is a cutaneous disease resulting from a defective barrier and dysregulated immune response. The severity scoring of atopic dermatitis (SCORAD) is used to classify AD. Noninvasive imaging approaches supplementary to SCORAD were investigated. Cr:forsterite laser‐based microscopy was employed to analyze endogenous third‐harmonic generation (THG) and second‐harmonic generation (SHG) signals from skin. Imaging parameters were compared between different AD severities. Three‐dimensional reconstruction of imaged skin layers was performed. Finally, statistic models from quantitative imaging parameters were developed for predicting disease severity. Our data demonstrate that THG signal intensity of lesional skin in AD were significantly increased and was positively correlated with AD severity. Characteristic gray level co‐occurrence matrix (GLCM) values were observed in more severe AD. In the 3D reconstruction video, individual dermal papilla and obvious fibrosis in the upper papillary dermis were easily identified. Our estimation models could predict the disease severity of AD patients with an accuracy of nearly 85%. The THG signal intensity and characteristic GLCM patterns are associated with AD severity and can serve as quantitative predictive parameters. Our imaging approach can be used to identify the histopathological changes of AD objectively, and to complement the SCORAD index, thus improving the accuracy of classifying AD severity.      

Diagnostic utility of APOE, soluble CD40, CD40L, and Abeta1-40 levels in plasma in Alzheimer's disease

A continuous inflammatory state is associated with Alzheimer's disease (AD) evidenced by an increase in proinflammatory cytokines around beta-amyloid (Abeta) deposits. In addition, functional loss of CD40L is shown to result in diminished Amyloid precursor proton (APP) processing and microglial activation, supporting a prominent role of CD40-CD40L in AD etiology. We therefore hypothesize that a peripheral increase in Abeta may result in corresponding increase of sCD40 and sCD40L further contributing to AD pathogenesis. We measured plasma Abeta, sCD40 and sCD40L levels in 73 AD patients and compared to 102 controls matched on general demographics. We demonstrated that Abeta(1-40), levels of sCD40 and sCD40L are increased in AD and declining MMSE scores correlated with increasing sCD40L, which in turn, correlated positively with Abeta(1-42). We then combined sCD40, sCD40L, Abeta and APOE and found that this biomarker panel has high sensitivity and specificity (>90%) as a predictor of clinical AD diagnosis. Given the imminent availability of potentially disease modifying therapies for AD, a great need exists for peripheral diagnostic markers of AD. Thus, we present preliminary evidence for potential usefulness for combination of plasma sCD40, sCD40L along with Abeta(1-40) and APOE epsilon4 in improving the clinical diagnosis of AD.     

Neuropsychological and behavioural correlates of CSF biomarkers in dementia

To improve clinical, neuropsychological and behavioural characterisation of the cerebrospinal fluid (CSF) biomarkers beta-amyloid((1-42)) protein (Abeta42), protein tau (tau) and tau phosphorylated at threonine 181 (P-tau181) across diagnostic dementia categories, a prospective study was set up. Patients with probable Alzheimer's disease (AD) (n=201), AD with cerebrovascular disease (CVD) (AD+CVD) (n=33), frontotemporal dementia (FTD) (n=27), dementia with Lewy bodies (DLB) (n=22) and healthy controls (n=148) were included. All patients underwent neuropsychological examination and behavioural assessment by means of a battery of behavioural assessment scales. CSF was obtained by lumbar puncture and levels of Abeta42, tau and P-tau181 were determined with commercially available ELISA kits. Negative correlations between CSF Abeta42 levels and aggressiveness (Spearman: r=-0.223; p=0.002) and positive correlations with age at inclusion (r=0.195; p=0.006), age at onset (r=0.205; p=0.003) and MMSE scores (r=0.198; p=0.005) were found in AD. In AD+CVD, CSF Abeta42 levels were correlated with MMSE (r=0.482; p=0.006), Hierarchic Dementia Scale (r=0.503; p=0.017) and Boston Naming Test (r=0.516; p=0.012) scores. In controls, age was positively correlated with CSF tau (r=0.465; p<0.001) and P-tau181 levels (r=0.312; p<0.001). CSF tau and P-tau181 levels correlated significantly in all groups, whereas CSF Abeta42 correlated with tau and P-tau181 levels in healthy controls only. Negative correlations between CSF Abeta42 levels and aggressiveness were found in AD patients. CSF Abeta42 seems to be a stage marker for AD (+/-CVD) given the positive correlations with neuropsychological test results suggesting that CSF Abeta42 might be of help for monitoring disease progression. Different correlations between age and CSF biomarker levels were obtained in healthy controls compared to AD patients, indicating that AD-induced pathophysiological processes change age-dependent regulation of CSF biomarker levels.     

A novel flow cytometric assay to quantify soluble CD14 concentration in human serum

BACKGROUND: CD14, the major lipopolysaccharide (LPS)-binding protein of myeloid cells, is found as a soluble molecule in human serum. Recent data describe the presence of elevated soluble CD14 (sCD14) concentration in various disorders, confirming disease activity. A novel, easy, and rapid flow cytometric assay was developed to measure sCD14 levels in serum. METHODS: The assay is based on the competition between membrane-expressed CD14 of isolated monocytes from healthy volunteers and sCD14 in the sample sera for binding to anti-CD14 monoclonal antibodies (mAb; 26ic or 60bca). The amount of cell-associated mAb is determined with a fluorescein isothiocyanate (FITC)-labeled anti-mouse conjugate and flow cytometry. The fluorescence signal is inversely proportional with the amount of serum sCD14. Using dilutions of a standard serum, the concentration of sCD14 in the samples is calculated and compared with results obtained by a commercial sCD14 enzyme-linked immunosorbent assay (ELISA). RESULTS: After optimization, the assay showed log-log linearity of 122.1-984.7 ng/ml sCD14 using mAb 26ic and 29.5-246.2 ng/ml sCD14 using mAb 60bca. It revealed similar results as the ELISA (mAb 26ic: r = 0.88, mAb 60bca: r = 0.92) and provided significantly elevated sCD14 levels in systemic lupus erythematosus patients compared with controls (26ic: 2,213 versus 1,676 ng/ml, P < 0.002; 60bca: 2,625 versus 1,907 ng/ml, P < 0.0002). Receiver operating characteristic curve analysis suggested a reasonable diagnostic efficacy of sCD14 quantification in this autoimmune disease. CONCLUSIONS: The method is easy, rapid, sensitive, and can be used in the follow-up of patients suffering from sepsis or chronic inflammatory disorders.     

Clinical Significance of Soluble Hemoglobin Scavenger Receptor CD163 (sCD163) in Sepsis, a Prospective Study

Objective

We investigated serum soluble CD163 (sCD163) levels for use in the diagnosis, severity assessment, and prognosis of sepsis in the critical ill patients and compared sCD163 with other infection-related variables.

Methods

During july 2010 and April 2011, serum was obtained from 102 sepsis patients (days 1, 3, 5, 7, and 10 after admission to an ICU) and 30 systemic inflammatory response syndrome (SIRS) patients with no sepsis diagnosed. Serum levels of sCD163, procalcitonon (PCT), and C reactive protein (CRP) were determined respectively. Sequential organ failure assessment (SOFA) scores for sepsis patients were also recorded. Then evaluated their roles in sepsis.

Results

The sCD163 levels were 0.88(0.78–1.00)ug/mL for SIRS patients, 1.50(0.92–2.00)ug/mL for moderate sepsis patients, and 2.95(2.18–5.57)ug/mL for severe sepsis patients on day1. The areas under the ROC curves for sCD163, CRP, and PCT for the diagnosis of sepsis were, respectively, 0.856(95%CI: 0.791–0.921), 0.696(95%CI: 0.595–0.797), and 0.629(95%CI: 0.495–0.763), At the recommended cut-off 1.49 ug/mL for sCD163, the sensitivity is 74.0% with 93.3% specificity. Based on 28-day survivals, sCD163 levels in the surviving group stay constant, while they tended to gradually increase in the non-surviving group.The area under the ROC curve for sCD163 for sepsis prognosis was 0.706(95%CI 0.558–0.804). Levels of sCD163 with cut-off point >2.84 ug/mL have sensitivity of 55.8.0%, specificity 80.4%.Common risk factors for death and sCD163 were included in multivariate logistic regression analysis; the odds ratios (OR) for sCD163 and SOFA scores for sepsis prognosis were 1.173 and 1.396, respectively (P<0.05). Spearman rank correlation analysis showed that sCD163 was weakly, but positively correlated with CRP, PCT, and SOFA scores (0.2< r <0.4, P<0.0001), but not with leukocyte counts (r <0.2, P = 0.450).

Conclusion

Serum sCD163 is superior to PCT and CRP for the diagnosis of sepsis and differentiate the severity of sepsis. sCD163 levels were more sensitive for dynamic evaluations of sepsis prognosis. Serum sCD163 and SOFA scores are prognostic factors for sepsis.

Trial Registration

www.chictr.org ChiCTR-ONC-10000812      

Diagnostic utility of anti-cyclic citrullinated peptide and anti-modified citrullinated vimentin antibodies in rheumatoid arthritis

Several autoantibodies found in RA are directed to epitopes in citrullinated proteins. One of them is anti modified citrullinated vimentin (Anti-MCV). We tested the value a newly developed ELISA for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with an anti-CCP based ELISA system for the diagnosis of RA. Thirty-five patients with RA (mean age; 42.6 +/- 10.87 years, mean disease duration; 9.37 +/- 3.98 years) were enrolled in this study. Twenty -five ankylosing spondylitis (mean age; 35.88 +/- 6.64 years, mean disease duration; 10.25 +/- 4.61 years), and 19 healthy subjects (mean age; 40.26 +/- 5.11 years) served as controls. Anti-CCP antibodies and Anti-MCV antibodies were measured using ELISA. In all RA patients, mean anti- CCP level was 69.07 +/- 90.43 U/ml and anti-MCV level was 665.77 +/- 1040.19 U/ml. In patients with AS, the mean anti-CCP level was 10.7 +/- 5.22 U/ml and anti-MCV level was 40.54 +/- 20.15 U/ml. In healthy controls, the mean anti-CCP level was 11.11 +/- 7.65 U/ml, anti-MCV level was 23.12 +/- 12.04 U/ml. In patients with active RA, the mean serum anti-CCP level was 100.54 +/- 98.07 U/ml and anti-MCV level was 998.74 +/- 1154.93 U/ml. In patients with inactive RA, the mean serum anti-CCP level was 8.77 +/- 1.55 U/ml and anti-MCV level was 27.59 +/- 23.10 U/ml. According to these results; In patients with RA, the mean serum anti-MCV and anti-CCP levels were significantly high compared to patients with AS and healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean serum anti-MCV and anti- CCP levels were significantly higher in active patients with RA than in inactive patients with RA patients (p=0.001 and p=0.001 respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP levels were similar in patients with AS and patients (p=0.484, p=0.308, p=0.09 and p=0.222 respectively). The mean serum anti-MCV levels were correlated with DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001), serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). As a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and combined use of anti-MCV and RF may be more useful prognostic factor than either method alone, RF and anti-CCP.     

Serum and lymphocyte levels of heat shock protein 70 in aging: a study in the normal Chinese population

Heat shock proteins (Hsps) have been reported to play an important role in both physiological and pathological processes. Hsps also may serve as biomarkers for evaluating disease states and exposure to environmental stresses. Whether Hsp levels in serum and lymphocytes are correlated with age and sex is largely unknown. In this study, we analyzed serum Hsp70 (the most abundant mammalian Hsp) levels by using Western dot blot in 327 healthy male donors aged between 15 and 50 years. We also investigated the association between Hsp70 levels and age in lymphocytes of 80 normal individuals aged between 40 and 77 years because various chronic diseases increase after the age of 40 years. Our data showed that serum Hsp70 levels were positively correlated with age in subjects aged between 15 and 30 years (P < 0.05) but negatively correlated with age in subjects aged between 30 and 50 years (P < 0.05). Serum Hsp70 levels were the highest in individuals aged between 25 and 30 years among all age groups. In the lymphocyte study there also was a significant age-related decrease in Hsp70 levels in lymphocytes of individuals older than 40 years. The Hsp70 levels were negatively correlated with age (r = -3.708, P < 0.0001) but not with sex (r = -10.536, P = 0.452). This suggests that both serum and lymphocyte Hsp70 levels are age-related and that these may be linked to age-related stress. Thus, age is an important factor in using serum and lymphocyte Hsp70 as biomarkers to evaluate the disease states or exposure to environmental stresses (or both).     

Profiling of Serum and Urinary MicroRNAs in Children with Atopic Dermatitis

Background

Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in children characterized by dermatitis and pruritus. MicroRNAs (miRNAs) have been shown as great potential biomarkers for disease fingerprints to predict prognostics. We aimed to identify miRNA signature from serum and urine for the prognosis of AD patient by genome-wide miRNA profiling analysis.

Methods

Serum and urine from 30 children with AD and 28 healthy children were collected and their genome-wide miRNA expression profiles were measured by TaqMan-based array and confirmed by quantitative real-time PCR. Inflammatory factors in serum were detected by Antibody Array System.

Results

miR-203 and miR-483-5p were significantly up-regulated in serum of children with AD compared with healthy children. The level of miR-483-5p in serum was significantly associated with other atopic conditions, such as rhinitis and/or asthma. However, miR-203 was markedly decreased in urine of children with AD compared with healthy children. Down-regulated miR-203 in urine was significant associated with abnormal level of serum IgE in AD patients. 7 inflammatory factors in serum were altered in children with AD compared with healthy children. Up-regulated miR-203 in serum was significantly associated with increased sTNFRI and sTNFRII.

Conclusions

Up-regulated miR-483-5p in serum may be indicative of other atopic conditions in children with AD. Down-regulated miR-203 in urine may serve as a biomarker for the severity of inflammation in children with AD.     

Differential levels of soluble endoglin (CD105) in myeloid malignancies

Angiogenesis contributes to disease progression in solid and hematopoietic malignancies, and endoglin (CD105), a component of the transforming growth factor (TGF)-beta receptor complex, is a powerful marker of neovascularization. Elevated amounts of soluble CD105 (sCD105) have been recently identified in selected solid tumors but no data are available on sCD105 in hematopoietic malignancies. Therefore, levels of sCD105 were investigated in sera of patients with acute myeloid leukemia (AML) (n = 10) or chronic myeloproliferative disorders (CMD) (n = 28), and correlated with those of soluble TGF-beta(1) (sTGF-beta(1)). Dot blot assay detected higher amounts of sCD105 (P < 0.05) both in AML (4.34 +/- 2.62 OD/mm(2)) and in CMD (3.71 +/- 2.09 OD/mm(2)) patients than in healthy subjects (n = 14, 2.38 +/- 1.18 OD/mm(2)). Instead, enzyme-linked immunosorbent assay (ELISA) identified (P < 0.05) lower and higher levels of sTGF-beta(1) in AML (32,017 +/- 1,900 pg/ml) and CMD (60,700 +/- 19,200 pg/ml) patients, respectively, compared to healthy individuals (n = 11, 47,173 +/- 5,443 pg/ml). In essential thrombocythemia (ET) patients with thrombotic episodes, levels of sCD105 were lower (P < 0.05) compared to patients without thrombotic complications, and inversely correlated with those of sTGF-beta(1) (r = 0.94). Conversely, amounts of sCD105 directly correlated with levels of sTGF-beta(1) (r = 0.74) in ET patients without thrombotic events. Our results show that high levels of sCD105 are present in myeloid malignancies that are characterized by a high cellular proliferation rate, and suggest that an altered balance between sCD105 and sTGF-beta(1) might favor disease progression and clinical complications.     

Soluble interleukin-2 receptor (sCD25) and interleukin-10 plasma concentrations are associated with severity of primary respiratory syncytial virus (RSV) infection

The role of the immune response in the severity of RSV infection was examined by determining plasma concentrations of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), interleukin-2 receptor (sCD25) and soluble tumor necrosis factor receptor II (sTNFR-II) in 196, previously healthy infants, during acute and convalescence phases of primary RSV infection. The results were analyzed separately for days 1-4 (early) and days 5-7 (late) of symptoms before sample collection and according to disease severity (105 hypoxic, 91 non-hypoxic). Significant associations between plasma levels and severity were found in early samples only. IL-10 and sCD25 concentrations were higher (p=0.01, each) in hypoxic compared with non-hypoxic infants, whereas no differences were observed in IFN-gamma and sTNFR-II levels between the groups. Early sCD25 levels correlated positively with IL-10 concentrations (p= 0.0003; r= 0,401). Amongst the hypoxic infants, the number of days of oxygen supplementation correlated positively with early IL-10 levels (p=0.009; r=0.495) and negatively with the IFN-gamma/IL-10 ratio (p=0.007; r=0.495). IFN-gamma levels were significantly higher in the acute phase than during convalescence for hypoxic and non-hypoxic infants, while IL-10 levels were significantly higher in the acute phase only in hypoxic infants for days 1-4 (early; p=0.0007). sCD25 concentrations were elevated only in hypoxic infants at days 1-4 of the acute phase (p=0.002), whereas sTNFR-II levels did not vary between acute and convalescence phases, independent of severity and time point of sampling. We found no association between plasma levels during the convalescence phase and the severity of the RSV infection.     

冠心病患者血清sCD40L水平及其与hs—CRP关系研究

目的：研究冠心病患者血清sCD40L和hs-CRP临床特点及其关系,探讨其在冠心病预测和治疗中的意义。方法：采用夹心法酶联免疫吸附测定分析法及微粒子增强透射免疫分析法分别对对照组15例、稳定型心绞痛（SAP）组27例、不稳定型心绞痛（UAP）组35例及急性心肌梗死（AMI）组14例受试者血清sCD40L和hs—CRP水平进行检测,并观察其与冠脉狭窄程度的相关性。结果：1）、血清hs-CRP水平：SAP组、UAP组、AMI组呈依次递增（AMI组比UAP组、UAP组比SAP组P〈0．05．AMI组、UAP组比对照组（P〈0．01）;SAP组与对照组血清hs—CRP水平相似;2）、血清sCD40L水平：AMI组及UAP组血清sCD40L水平高于SAP组和对照组（P〈0．01）,AMI组与UAP组之间、SAP与对照组间没有统计学差异;3）、相关分析显示血清sCD40L水平与hs-CRP水平显著相关（r=0．787,P〈0．0001）,两者均与冠脉狭窄程度无相关性。结论：血清hs-CRP、sCD40L水平升高与冠心病临床表现类型和病情是否稳定有关,与冠状动脉狭窄程度无关,此两项指标能够用于冠心病病情不稳定性的判断和预测。     

Comparative platelet proteome analysis reveals an increase of monoamine oxidase-B protein expression in Alzheimer's disease but not in non-demented Parkinson's disease patients

Monoamine oxidase-B (Mao-B) catalysing the breakdown of the neurotransmitter dopamine, is known to be involved in the pathophysiology of Parkinson's (PD) and Alzheimer's disease (AD). Increased brain Mao-B activity is associated with AD. This alteration can also be seen in platelets, albeit the cause has hitherto remained elusive. To gain a deeper understanding of the etiology of AD, the platelet proteome was characterised, (2D DIGE pH6-9, including Mao-B) from 150 individuals: 34 AD, 13 vascular dementia, 15 non-demented PD patients, 49 matched controls, 18 oldest old and 21 young individuals. One significant change was noted after applying false discovery rate with the upregulation of the Mao-B expression (30% adjusted P value<0.001; effect size 1.31) in AD compared to age- and sex-matched controls. In contrast, Mao-B levels were unchanged in PD to matched controls. Western blot and mRNA analyses verified these findings. Moreover, Mao-B concentration correlated with age in the cognitive healthy individuals (r=0.53; P<0.001) and PD patients but not in those suffering from AD (r=-0.03; P=0.874). Mao-B activity correlated with the increased Mao-B protein expression in AD (r=0.81; P=0.016). We suggest that Mao-B platelet protein level may serve as a biomarker for age-related dementia, especially AD.     

Indoor Air Pollution Aggravates Symptoms of Atopic Dermatitis in Children

Most of researches on the impact of indoor air pollutants on atopic dermatitis (AD) have been based upon animal models, in vitro experiments and case-control studies. However, human data to elucidate the role of indoor air pollution on worsening symptoms of pre-existing AD from a longitudinal study are scarce. The objective of this prospective study was to evaluate the effect of indoor air pollution on AD symptoms in children. We surveyed 30 children with AD in a day-care centre, which moved to a new building during the study. These children stayed there for 8 hours a day Monday through Friday, and their daily symptom scores were recorded. Indoor and outdoor air pollutant levels were continuously measured 24 hours a day for 12 months (Period 1 to 4). Data were analyzed using a generalized linear mixed model. Compared to the period before moving (Period 1), concentrations of indoor air pollutants mostly increased after moving (Period 2) and decreased by natural ventilation and bake-out (Periods 3 and 4). The rate of positive AD symptom increased from 32.8% (Period 1) up to 43.8% (Period 2) and 50.5% (Period 3), then decreased to 35.4% in Period 4 (P < 0.0001). When the delayed effects of indoor air pollutants on AD symptoms 2 days later were evaluated, AD symptoms significantly increased by 12.7% (95% CI: -0.01 to 27.1) as toluene levels increased by 1 ppb (P = 0.05). In conclusion, indoor air pollutants increase the risk of AD aggravation in children and toluene in the indoor environment might act as an aggravating factor.     

Atopic dermatitis: insights from linkage overlap and disease co-morbidity

Atopic dermatitis (AD) is a strongly heritable, chronic relapsing dermatosis that frequently co-occurs with other atopic phenotypes including asthma and allergic rhinitis (the so-called atopic triad disorders). However, despite high levels of co-morbidity, relatively low levels of genomic co-incidence have been observed between atopic triad disorders. Conversely, current mapping data have revealed a striking pattern of co-localisation between AD disease loci and those mapped using another chronic dermatological disease - psoriasis. In this review, we examine the evidence for co-localisation between AD and a range of atopic, infectious, inflammatory and autoimmune diseases, and consider the implications of these data for the AD disease concept and future research in the field.     

Genetic variants of the receptors for thromboxane A2 and IL-4 in atopic dermatitis

Thromboxane A2 (TXA2) is an arachidonate metabolite which is considered to relate to chronic inflammation in atopic diseases characterized by elevated immunoglobulin E productivity. The elevation of immunoglobulin E levels involves many molecules including interleukin-4 (IL-4) and interleukin-4 receptor alpha chain (IL-4R alpha). To assess whether genetic variants of TXA2 receptor, IL-4 and IL-4R alpha genes relate to the elevation of serum immunoglobulin E levels in patients with atopic dermatitis (AD), we conducted an association study of genetic polymorphisms of TXA2 receptor (795C/T), IL-4 (-589C/T), and IL-4R alpha (Ile50Val) in a Japanese population (n = 789). The TXA2 receptor 795TT genotype strongly related to AD with high serum immunoglobulin E concentrations. AD patients with both TXA2 receptor 795TT genotype and the IL-4R alpha Ile50/Ile50 genotype showed the greatest immunoglobulin E concentrations. These results suggest TXA2 receptor polymorphism strongly interacts with IL-4R alpha polymorphism as a major determinant of high serum immunoglobulin E levels in AD.     

Plasma levels of soluble CD36, platelet activation, inflammation, and oxidative stress are increased in type 2 diabetic patients

Inflammation, oxidative stress, and platelet activation are involved in type 2 diabetes and its complications. Soluble CD36 (sCD36) has been proposed to early identify diabetics at risk of accelerated atherothrombosis. We aimed at characterizing the platelet contribution to sCD36 in diabetes, by correlating its concentration with the extent of platelet-mediated inflammation and in vivo lipid peroxidation and investigating the effects of low-dose aspirin on these processes. A cross-sectional comparison of sCD36, soluble CD40L (sCD40L) reflecting platelet-mediated inflammation, urinary 11-dehydro-TxB(2), and 8-iso-PGF(2α), in vivo markers of platelet activation and lipid peroxidation, was performed among 200 diabetic patients (94 of them on aspirin 100mg/day) and 47 healthy controls. sCD36 levels (median [IQR]: 0.72 [0.31-1.47] vs 0.26 [0.2-0.37], P=0.003) and urinary 11-dehydro-TxB(2) levels (666 [293-1336] vs 279 [160-396], P≤0.0001) were significantly higher in diabetic patients not on aspirin (n=106) than in healthy subjects. These variables were significantly lower in aspirin-treated diabetics than untreated patients (P<0.0001). Among patients not on aspirin, those with long-standing diabetes (>1 year) had significantly higher sCD36 levels in comparison to patients with diabetes duration <1 year (1.01 [0.62-1.86] vs 0.44 [0.22-1.21], P=0.001). sCD36 linearly correlated with sCD40L (rho=0.447; P=0.0001). On multiple regression analysis, 11-dehydro-TxB(2) (β=0.360; SEM=0.0001, P=0.001), 8-iso-PGF(2α) (β=0.469; SEM=0.0001, P<0.0001), and diabetes duration (β=0.244; SEM=0.207, P=0.017) independently predicted sCD36 levels. sCD36, platelet activation, inflammation, and oxidative stress are increased in type 2 diabetes. Future studies are needed to elucidate if the incomplete down-regulation of sCD36 by low-dose aspirin implies that sCD36 may be derived from tissues other than platelets or if additional antiplatelet strategies in diabetes are necessary to interrupt CD36-dependent platelet activation.     

Markers of atopic dermatitis,allergic rhinitis and bronchial asthma in pediatric patients: correlation with filaggrin,eosinophil major basic protein and immunoglobulin E

Background

Allergic reactions have been implicated as contributions in a number of atopic disorders, including atopic dermatitis (AD), allergic rhinitis (AR) and bronchial asthma (BA). However, the potential for filaggrin protein, eosinophil major basic protein (MBP) and immunoglobulin E (IgE) to elicit allergic response or to contribute to atopic disorders remains largely unexplored in pediatric patients. This study was undertaken to investigate the status and contribution of filaggrin protein, eosinophil MBP and total IgE in pediatric patients with AD, AR and BA.

Methods

Sera from 395 pediatric patients of AD, AR or BA with varying levels of disease activity according to the disease activity index and 410 age-matched non-atopic healthy controls were evaluated for serum levels of atopic markers, including filaggrin, eosinophil MBP and IgE.

Results

Serum analysis showed that filaggrin levels were remarkably high in pediatric patients with AD, followed by BA and AR, whereas its levels were low in non-atopic pediatric controls. Eosinophil MBP levels in sera of atopic patients were significantly high as compared with their respective controls, but its levels were highest in AR patients, followed by AD and BA. Total IgE in sera of AD patients was markedly high, followed by AR and BA patients, whereas its levels were low in non-atopic pediatric controls. Interestingly, not only was an increased number of subjects positive for filaggrin protein, eosinophil MBP or total IgE, but also their levels were statistically significantly higher among those atopic patients whose disease activity scores were higher as compared with atopic patients with lower disease activity scores.

Conclusions

These findings strongly support a role of filaggrin protein, eosinophil MBP and IgE in the onset of allergic reactions in pediatric patients with AD, AR and BA. The data suggest that filaggrin, eosinophil MBP or IgE might be useful in evaluating the progression of AD, AR or BA and in elucidating the mechanisms involved in the pathogenesis of these pediatric disorders.