Disease Activity In Atopic Dermatitis Research Articles

THE ROLE OF ANTIFUNGAL THERAPY IN THE TREATMENT OF ATOPIC DERMATITIS IN CHILDREN

Relevance. Atopic dermatitis (AD) is a common multifactorial disease in which allergens from the yeast Malassezia can worsen the severity of the disease. Local application of antimycotic drugs can reduce the allergen load on the skin and improve its condition.
 Objective: The aim of this study was to evaluate the effectiveness of ketoconazole 2% cream in the treatment of AD in children as an additional therapy, and the effect of sensitization to Malassezia and polymorphism rs7309123 in the Dectin-1 gene on the effectiveness of treatment.
 Materials and methods. 54 patients with atopic dermatitis aged 6-18 years were included in the study. Patients were randomized into two groups: a group receiving ketoconazole cream 2% (n=28) and a control group (n=26). Specific IgE to Malassezia was analyzed in 28 patients of the main group. Genotyping of the rs7309123 polymorphism in the Dectin-1 gene was performed in a group of patients using real-time PCR. Atopic dermatitis disease activity was evaluated before and after treatment using the SCORAD.
 Results. Improvement was observed in both groups of children in 3 weeks after treatment (p<0,001). Children who received ketoconazole in addition to therapy had significantly better dynamics of the severity indicator, compared to the control group (W=465,0, p<0,001). The rs7309123 polymorphism in the Dectin-1 gene affected the effectiveness of treatment: ΔSCORAD in the subgroup of children with the CC and CG genotypes was significantly higher than in the subgroup of children with the pathological GG genotype (20,2±11,5 and 13±6,5, respectively, T=2,12, p=0,044).
 Conclusion. This study demonstrated the effectiveness of ketoconazole in the treatment of atopic dermatitis as an additional therapy.

Аналіз ефективності дворічного курсу алерген-специфічної імунотерапії в дітей з атопічним дерматитом та сенсибілізацією до кліщів домашнього пилу

Atopic dermatitis is a chronic inflammatory skin disease that affects 15% to 30% of children and 2% to 10% of adults worldwide. Some observations suggest that allergens may be an important cause of atopic dermatitis. Allergen-specific immunotherapy can reduce symptoms in people with atopic dermatitis by suppressing abnormal immune responses to allergens. Purpose - to evaluate the role of sublingual immunotherapy in the treatment of atopic dermatitis in children with sensitization to house dust mite, by conducting a randomized 24-month clinical trial with house dust mite extract. Materials and methods. The study included 26 children with atopic dermatitis, sensitized to house dust mites. 12 patients received sublingual immunotherapy and 14 patients received only symptomatic treatment (the control group). The disease activity of atopic dermatitis was evaluated using the dynamics of SCORAD indicators and the CDLQI questionnaire. Results. After 24 months from the start of treatment, the decrease in SCORAD was 52.1% in the sublingual immunotherapy group (Wilcoxon T-test, T-W=78.0; p<0.001) and 20.2% in the control group. The decrease in CDLQI after 24 months was 40% in the sublingual immunotherapy group (T-W=66.0; p<0.001), in the control group no improvement was found. We have not found influence of age and degree of severity on the effectiveness of therapy. Conclusions. This randomized 2-year study showed that sublingual immunotherapy with house dust mite extract can provide significant clinical efficacy according to SCORAD and CDLQI questionnaire in children with atopic dermatitis. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

399 Real-world effectiveness and safety of baricitinib in Japanese patients with atopic dermatitis: possible suppressive effect of serum IL-22 levels by baricitinib

Baricitinib, an oral, selective, and reversible Janus kinase 1/2 inhibitor, has been used for moderate-to-severe AD in patients aged >15 years in Japan from December 2020. In this study, we analyzed 14 Japanese adult patients with moderate-to-severe atopic dermatitis who were treated with baricitinib at Gunma University Hospital. We present our real-world data in combination with hematological data and improvement rates, and the relationship between serum interleukin-22 levels and disease activity of atopic dermatitis.

207 The impact of childhood stressful life events on atopic dermatitis disease activity and severity: A prospective study

Stress has been associated with atopic dermatitis (AD), however, longitudinal data on the association with AD course are limited. We aimed to examine whether stressful life events are associated with increased AD disease activity and severity throughout childhood using the Avon Longitudinal Study of Parents and Children prospective English birth cohort, comprised of 13,972 children with assessments from birth. The primary exposure was a standardized, age-appropriate scale of stressful life events repeated at 7 times points between ages 1.5 and 8.5. The primary outcome was a repeated measure of AD period prevalence, as defined by caregiver-reported symptoms of flexural dermatitis. The annual period prevalence of AD ranged from 18-21%. For each standard deviation (SD) increase in stressful life events across childhood there was an increased risk of AD activity (OR: 1.07; 95% CI 1.04-1.16), and the association was largest with severe disease (OR 1.13, 95%CI 1.02-1.23). There was no effect modification by the presence of filaggrin gene null mutations or history of asthma or rhinitis. Given the nature of the stressful life events measured, reverse causality is not likely to be an explanation for the results. In a large, prospective, population-based study, we found that stressful life events in childhood confer a small, but significant, risk in increased AD activity and severity. These findings suggest that the impact of stress-reducing interventions should be further investigated in those with AD.

14402 Serum levels of thymus and activation-regulated chemokine in patients with psoriasis: Higher in patients with generalized pustular psoriasis

Thymus and activation-regulated chemokine (TARC) is designated a TH2 type chemokine. Serum TARC levels sharply reflect the disease activity of atopic dermatitis. The previous studies reported that serum TARC levels in patients with psoriasis vulgaris (PsV) were comparable with those in healthy controls, however, we sometimes encounter psoriasis patients with high serum levels of TARC. The association of clinical severity of psoriasis with serum TARC levels has not been investigated yet. Furthermore, to date, serum TARC levels in patients with psoriatic arthritis (PsA) or generalized pustular psoriasis (GPP) have never been reported. Thereby, we investigated the association of serum TARC levels with psoriasis by types of psoriasis, and examined correlations of serum TARC levels with clinical severity scores and other results of blood tests. Psoriasis patients visiting our hospital from April 2013 to April 2018 were included in this study. All data were collected retrospectively from the patient charts. Data on 75 patients (51 men and 24 women; PsV 30 patients, PsA 29 patients, GPP 16 patients) were analyzed. The serum TARC levels in patients with GPP were significantly higher than those in PsV and those in PsA. There was significantly positive correlation between serum TARC levels and PASI scores. In conclusion, our study revealed that serum TARC levels were high in patients with GPP. Furthermore, serum TARC levels can potentially be one of biomarkers reflecting the severity or systemic inflammation caused by psoriasis in patients with psoriasis, not so much as in patients with atopic dermatitis.

16825 Passively collected data from smartphones correlate with subjective disease severity in atopic dermatitis

Introduction: Atopic dermatitis (AD) often fluctuate in intensity with changes in sleep, activity-levels, stress and weather conditions including pollen. As objective data confirming these factors’ association with AD disease activity is limited, we utilized smartphone data in a fully virtual trial to investigate their association over time.

482 Longitudinal cohort study of the association between atopic dermatitis and depression throughout childhood

Atopic dermatitis (AD) is one of the most common inflammatory diseases of childhood and has been associated with comorbid mental health outcomes, but there are limited data on the development of depression during childhood and adolescence, which may be a critical period for intervention. To understand origins of the relationship between AD and depression, accounting for heterogeneity in AD disease activity and severity over time, we analyzed data from an existing longitudinal cohort study representative of the UK population including 13,979 children followed from birth into adolescence. AD annual period prevalence and severity were measured using a standardized and validated question about flexural dermatitis; depressive symptoms were measured using the Short Moods and Feelings Questionnaire (SMFQ) at multiple ages. Period prevalence of AD ranged from 12.8%-18.6%, and clinically significant depressive symptoms ranged from 6.0% -17.9%. Using cross-sectional multivariable logistic regression, we tested the hypothesis that active AD in the past year was associated with SMFQ scores at 5 time points between ages 10 and 16. After controlling for potential confounders including sex, ethnicity, asthma/rhinitis, socioeconomic status and maternal mental health, we found that any active AD was associated with a 13-46% increase in the odds of depression, but the association was only significant at age 16 (OR:1.46, 95%CI 1.04-1.90), and that participants with moderate/severe disease consistently had higher odds of depression. Including a history of asthma or allergies as potential mediators did not substantially change the effect sizes. When inflammatory markers linked to depression (IL-6 and CRP) were additionally included in the models, effect sizes did not change, suggesting that other markers or mechanisms are likely to explain the association. Our results highlight the importance of interventions to address depression among children with AD, especially those with more severe disease and active disease during adolescence.

Correlation of Blood FoxP3+ Regulatory T Cells and Disease Activity of Atopic Dermatitis.

Objectives To investigate CD4+CD25+FoxP3+ T regulatory cells (Tregs) in the peripheral blood of patients with atopic dermatitis (AD) and its correlation with disease severity. Methods Blood samples from 79 AD patients before and after four-week conventional treatment were collected. Cell counts of CD4+CD25+FoxP3+Tregs, CD4+CD25+FoxP3-T effector cells (Teffs), and CD4+IL-10+Tregs were analyzed by flow cytometry. Serum levels of IL-4, IL-10, IL-12, IL-13, IFN-γ, and TGF-β were measured by ELISA. Results The pretreatment cell count of CD4+CD25+FoxP3+Tregs positively correlated with disease severity in all patients (P < 0.0001). However, when that correlation was rechecked based on the treatment response, a much stronger correlation of that was found in those patients with remission after treatment, while no correlation of that was found in patients without remission. Both the cell count and proportions of peripheral CD4+CD25+FoxP3+Tregs and CD4+CD25+FoxP3-Teffs reduced significantly after treatment in patients with remission, but remained unchanged in patients without remission. The cell count and proportion of CD4+IL-10+Tregs did not change after treatment in both groups. In patients with remission, serum levels of IL-4 and IL-13 significantly reduced (all P < 0.05); IL-12 and IFN-γ levels increased significantly (all P < 0.05); IL-10 and TGF-β levels remained unchanged after treatment. None of those cytokine levels changed in patients without remission. Conclusions CD4+CD25+FoxP3+Tregs is associated with AD development and severity in some patients but not in others. AD maybe divided into CD4+CD25+FoxP3+Treg-associated subtype, which CD4+CD25+FoxP3+Treg is parallel to the activity of AD, and nonassociated subtype, which CD4+CD25+FoxP3+Treg is not related. This subgroup difference may contribute partly to the nonidentical markers that have been found in AD and should be studied further.

IL-4 Augments IL-31/IL-31 Receptor Alpha Interaction Leading to Enhanced Ccl 17 and Ccl 22 Production in Dendritic Cells: Implications for Atopic Dermatitis.

Severe pruritus is a characteristic feature of atopic dermatitis (AD) and is closely related to its activity. Recent studies have shown that IL-31 is a key determinant of pruritus in AD. Anti-IL-31 receptor alpha (IL-31RA) antibody treatment has also been reported to improve pruritus clinically, subsequently contributing to the attenuation of AD disease activity. Therefore, IL-31 has been thought to be an important cytokine for regulating pruritus and AD disease activity; however, how IL-31 is involved in the immune response in AD has remained largely unknown. Epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) derived from bone marrow cells have been reported to play a critical role in AD pathogenesis. LCs and DCs produce Ccl 17 and Ccl 22, which chemoattract Th2 cells, leading to AD development. Therefore, we aimed to clarify how IL-31/IL-31RA interaction affects Ccl 17 and Ccl 22 production. To test this, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-4, an important cytokine in AD development. We found that IL-31RA expression was upregulated by IL-4 stimulation in a dose-dependent manner in BMDCs. Furthermore, IL-31 upregulates Ccl 17 and Ccl 22 production in the presence of IL-4, whereas IL-31 stimulation alone did not produce Ccl 17 and Ccl 22. These findings suggest that IL-4 mediates IL-31RA expression and IL-31/IL-31RA interaction augments Ccl 17 and Ccl 22 production in BMDCs, which promotes Th2-deviated immune response in AD. Since we previously reported that soybean tar Glyteer, an aryl hydrocarbon receptor (AHR) ligand, impairs IL-4/Stat 6 signaling in BMDCs, we examined whether Glyteer affects IL-31RA expression induced by IL-4 stimulation. Glyteer inhibited upregulation of IL-31RA expression induced by IL-4 stimulation in a dose-dependent manner. Glyteer also inhibited Ccl 17 and Ccl 22 production induced by IL-4 and IL-31 stimulation. Taken together, these findings suggest that Glyteer treatment may improve AD disease activity by impairing IL-31/IL-31RA interaction in DCs.

299 IL-31/IL-31 receptor alpha interaction augments IL-4-induced Ccl 17 and Ccl 22 production in dendritic cells

One of characteristic features of atopic dermatitis (AD) is severe pruritus that is closely related to disease activity. Recent studies have shown that IL-31 is one of key determinants of pruritus in AD. Furthermore, anti-IL-31 receptor alpha (IL-31RA) antibody treatment has been reported to show a clinical improvement of pruritus. Therefore, IL-31 has been thought to be an important cytokine to regulate pruritus and disease activity in AD; however, how IL-31 is involved in the immune response in AD has been largely unknown. Epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) derived from bone marrow cells have been reported to play a critical role in the pathogenesis of AD. LCs and DCs produce Ccl 17 and Ccl 22 that chemoattracts Th2 cells, which leads to the development of AD. Therefore, we aimed to clarify how IL-31/IL-31RA interaction affects functions of DCs including production of Ccl 17 and Ccl 22. To investigate this, we analyzed murine bone marrow derived-DCs (BMDCs) stimulated with IL-4. We found that IL-31RA expression was upregulated by IL-4 stimulation in a dose-dependent manner in BMDCs. Furthermore, IL-4 upregulated production of Ccl 17 and Ccl 22, which was enhanced by IL-31, whereas IL-31 alone did not produce them. These data suggest that IL-4 mediates IL-31RA expression and IL-31/IL-31RA interaction augments production of Ccl 17 and Ccl 22 in BMDC, which promotes Th2-deviated immune response in AD. Since we have previously reported that soy bean tar Glyteer, an aryl hydrocarbon receptor (AHR) ligand, impairs IL-4/Stat 6 signaling in BMDCs, we examined whether Glyteer affected IL-31RA expression induced by IL-4 stimulation. Glyteer inhibited upregulation of IL-31RA expression induced by IL-4 in a dose-dependent manner. Also, Glyteer inhibited production of Ccl 17 and Ccl 22 induced by IL-4 and IL-31. Taken together, these data suggest a possibility that treatment using AHR activators such as Glyteer and anti- IL-31RA antibody may synergistically improve pruritus and disease activitity of AD.

Correlation between Serum Interleukin-31 Level and the Severity of Atopic Dermatitis in Children

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by intense itch, typical localization and a specific image of skin lesions. Pathogenesis of pruritus in AD is not fully understood, but recent studies emphasize the role of interleukin-31 (IL-31). This relatively recently described cytokine is considered to be a potential mediator inducing pruritus in AD. Aim of the Work: was to assess the correlation of serum IL-31 level and the disease severity in children with AD. Patients and Methods: a case control study. Sera were obtained from 50 AD children and 30 healthy volunteers. IL-31 levels were measured using ELISA with standard kits from EIAab R&D Systems. Serum IL-31 levels were correlated with AD disease activity. Disease severity in children with AD was assessed using the SCORAD (Severity scoringof atopic dermatitis) index. Results: Serum IL-31 level was significantly higher in AD children (Mean ± SD 99.73 ± 75.93) than in healthy children (Mean ± SD 54.01 ± 57.36), (p-value = 0.019). Serum IL-31 levels correlated positively with the calculated severity score (SCORAD index), (rs = 0.480, p- value <0.001) Conclusion: The results of this study confirm the importance of IL-31 in AD pathophysiology. Serum IL-31 level is an objective reliable marker of AD severity in children. It may represent a novel target for antipruritic drug development.

Correlation between Serum Interleukin-31 Level and the Severity of Atopic Dermatitis in Children

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by intense itch, typical localization and a specific image of skin lesions. Pathogenesis of pruritus in AD is not fully understood, but recent studies emphasize the role of interleukin-31 (IL-31). This relatively recently described cytokine is considered to be a potential mediator inducing pruritus in AD. Aim of the Work: was to assess the correlation of serum IL-31 level and the disease severity in children with AD. Patients and Methods: a case control study. Sera were obtained from 50 AD children and 30 healthy volunteers. IL-31 levels were measured using ELISA with standard kits from EIAab R&D Systems. Serum IL-31 levels were correlated with AD disease activity. Disease severity in children with AD was assessed using the SCORAD (Severity scoringof atopic dermatitis) index. Results: Serum IL-31 level was significantly higher in AD children (Mean ± SD 99.73 ± 75.93) than in healthy children (Mean ± SD 54.01 ± 57.36), (p-value = 0.019). Serum IL-31 levels correlated positively with the calculated severity score (SCORAD index), (rs = 0.480, p- value <0.001) Conclusion: The results of this study confirm the importance of IL-31 in AD pathophysiology. Serum IL-31 level is an objective reliable marker of AD severity in children. It may represent a novel target for antipruritic drug development.

Anti-IL-33 Antibody Has a Therapeutic Effect in an Atopic Dermatitis Murine Model Induced by 2, 4-Dinitrochlorobenzene.

IL-33 is a new member of the IL-1 family that plays a role in allergic disease. In this study, we evaluated the potential on the inhibition of atopic dermatitis (AD) of anti-mouse IL-33 antibody (αIL-33Ab) using 2, 4-dinitrochlorobenzene (DNCB)-induced AD mice model. We treated mice with αIL-33Ab via subcutaneous injection of each DNCB treatment 1h later from day 1 to day 33 for 14 times. A control group received tacrolimus. Skin lesion and scratching behavior were compared. Ear thickness, dermatitis score, eosinophils and mast cells infiltration, and serum IgE levels were also analyzed. Correlations between serum IL-33 as well as soluble(s) ST2 and AD disease activity index in human AD were also investigated. DNCB-induced AD-like mice treated with αIL-33Ab showed improved AD-like symptoms. Eosinophils and mast cells infiltration and serum IgE levels were also significantly reduced by αIL-33Ab. Our study suggests that blockade of IL-33 has a curative effect on AD.

Eosinophil-derived neurotoxin as a biomarker for disease severity and relapse in recalcitrant atopic dermatitis

BackgroundEosinophils are encountered in many skin diseases, but the role of eosinophils in atopic dermatitis (AD) remains uncertain. ObjectiveTo examine the role of serum eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and total IgE as a biomarker of disease severity and relapse in severe recalcitrant AD. MethodsWe enrolled 99 patients with AD: 37 with severe recalcitrant AD, 20 with severe AD, and 42 with mild to moderate AD. We examined the difference in serum level of total IgE, ECP, and EDN between the groups and whether any correlation existed between disease severity and ECP or EDN. Lastly, difference in levels of ECP or EDN between those who experienced relapse was examined in the severe recalcitrant group. ResultsSerum levels of total IgE, ECP, and EDN were significantly higher in the severe recalcitrant AD group and severe AD group compared with the mild to moderate AD group. No significant difference was found in serum levels of total IgE, ECP, and EDN between the severe recalcitrant group and severe group. EDN had a significant positive correlation with the SCORing Atopic Dermatitis. No significant correlation was found between EDN and ECP. In the severe recalcitrant group, 29.7% of patients experienced relapse, and EDN was significantly higher in those who experienced relapse. The cutoff value of EDN for predicting relapse was 64.5. ConclusionEDN correlated with the disease severity of AD. EDN may predict relapse in severe recalcitrant AD. The EDN serum level could be considered a candidate molecule as a clinical biomarker for evaluating AD disease activity and a predictor of relapse.

Non-invasive evaluation of atopic dermatitis based on redox status using in vivo dynamic nuclear polarization magnetic resonance imaging

Atopic dermatitis (AD) is a chronic inflammatory condition with complex etiology, including genetic, environmental and immunologic factors. Redox imbalance caused by excessive oxidative stress has been shown to mediate disease activity of AD. Currently, an imaging technique that can monitor the redox status of the skin in vivo has not yet been developed. Consequently, we have established such a technique that can detect and visualize the redox status of the skin using in vivo dynamic nuclear polarization magnetic resonance imaging (DNP-MRI). To evaluate this technique, we utilized an AD mouse model that was generated by repeated topical application of mite antigen in NC/Nga mice. We imaged alterations in redox balance of the resulting AD skin lesions of the mice. Using in vivo DNP-MRI and non-toxic nitroxyl radicals to visualize free radicals in vivo, we revealed that AD skin lesions demonstrated more rapid decay rates of image intensity enhancement than normal skin, indicating that our technique can monitor excessive oxidative stress occurring in AD skin lesions. Therefore, this technique has the potential to provide a novel approach for evaluating disease activity of inflammatory skin diseases, including AD, from the view point of altered redox status.

Immunomodulatory Drugs (IMiDs), Lenalidomide and Pomalidomide, Suppress Th1-Inducing Capacity of Dendritic Cells but Enhance Th2-Mediated Allergic Response

Background: Analogs of thalidomide, lenalidomide (LEN) and pomalidomide (POM), are novel anti-multiple myeloma (MM) drugs (so-called Immunomodulatory Drugs; IMiDs). LEN has been reported to enhance function of effector immune cells such as T cells and NK cells and to induce selective reduction of regulatory T cells. Meanwhile, LEN and POM treatments lead to relatively high rate onset of itchy skin with rash like allergic reaction. However, cellular and molecular mechanisms underlying their immunomodulatory effects still remain largely unclear. Although there is evidence indicating the immunomodulatory actions of LEN on mouse conventional dendritic cells (DCs), there are few reports showing their effects on human DC subsets. DCs are pivotal in orchestrating both innate and acquire immunity as the center of the immune regulatory system, and series of analyses have clarified a functional plasticity of DCs to induce Th1 or Th2 response. Therefore, we focused on the effects of LEN and POM on the function of human myeloid DCs (mDCs), which are the major regulators to induce Th1 or Th2 responses and play a pathogenic role in allergy by their dysregulated Th2-inducing function (Ito T. J Exp Med 2005; 202: 1213).Methods: Using cell sorting, flow cytometry, real-time PCR, and ELISA methods, function and signaling were analyzed in blood human CD11+ mDCs from healthy adult volunteers. Sera were obtained from 24 MM patients with before and after LEN therapy. Written informed consent was obtained for all patients. This study was approved by the Institutional Review Board of Kansai Medical University.Results: We found that both agents at clinical in vivo plasma concentration of 0.1 µM to 1 µM did not affect the mDC survival and their CD86 and OX40-ligand expression in response to toll-like receptor (TLR)-ligands (LPS, poly IC, or R848) and Th2-inducing cytokine, thymic stromal lymphopoietin (TSLP) for 24 h culture. Either LEN or POM inhibited dose-dependently mDC-derived Th1-associated cytokines, IL-12 in response to R848 (1 µM LEN; 5.2 % of cont. and 0.3 µM POM; 12 % of cont.), IFN-λ in response to poly IC (1 µM LEN; 5.4 % of cont. and 0.3 µM POM; 10 % of cont.), and TNFα in response to R848 (1 µM LEN; 36 % of cont. and 0.3 µM POM; 17 % of cont.), but enhanced IL-10 production in response to R848 (1 µM LEN; 4.8-fold increase and 0.3 µM POM; 7.5-fold increase). When mDCs were stimulated with TSLP, both agents significantly enhanced the production of Th2-recruiting chemokine CCL17/TARC (1 µM LEN; 2.4 fold increase and 0.3 µM POM; 3.9 fold increase), which functions as chemoattractant for memory Th2 cells and contribute to aggravation of allergic inflammation. These capacities of POM were stronger than those of LEN. In addition, we revealed that, in response to LPS or R848, both LEN and POM downregulated not only IRF4 mRNA in human mDCs as in LEN-treated myeloma cells, but also STAT4 mRNA, which is important for DC-mediated Th1 response and IL-12 production. In mDCs treated with TSLP, both agents were found to upregulate STAT6 mRNA, which is responsible for TSLP-mediated CCL17 secretion (Arima K. Sci Signal2010;3:ra4). Clinically, serum CCL17/TARC levels are associated with the disease activity of atopic dermatitis and sensitively reflect short-term changes in skin conditions. We also found, in MM patients, serum CCL17 levels at the onset of LEN-associated rash during 4 weeks (n=9; 1271 ± 376 pg/ml) were significantly higher (p <0.001) compared to those without rash in LEN treatment (n=15; 476 ± 236 pg/ml) and those before treatment (296 ± 172 pg/ml).Conclusion: Our data suggest that the IMiDs, while suppress the Th1-inducing capacity of DCs, rather lead to enhance allergic response at DC phase through modulation of signaling pathways in this stream of action. Thus, IMiDs could have the potential to shift DC-mediated response from Th1 to Th2, and our findings provide a plausible explanation for pathogenesis of IMiD-associated rash in the treatment for MM. DisclosuresIto:Celgene corporation: Honoraria; GSK: Patents & Royalties.

Association of urinary biopyrrin with disease activity of atopic dermatitis in adults

Association of urinary biopyrrin with disease activity of atopic dermatitis in adults

Influence of Pre-Analytical Factors on Thymus- and Activation-Regulated Chemokine Quantitation in Plasma.

Thymus- and activation-regulated chemokine (TARC) in serum/plasma associates with the disease activity of atopic dermatitis (AD), and is a promising tool for assessing the response to the treatment of the disease. TARC also exists within platelets, with elevated levels detectable in AD patients. We examined the effects of pre-analytical factors on the quantitation of TARC in human EDTA plasma. TARC levels in platelet-free plasma were significantly lower than those in platelet-containing plasma. After freeze-thaw, TARC levels increased in platelet-containing plasma, but remained unchanged in platelet-free plasma, suggesting TARC was released from the platelets during the freeze-thaw process. In contrast, TARC levels were stable in serum independent of freeze-thaw. These findings underscore the importance of pre-analytical factors to TARC quantitation. Plasma TARC levels should be measured in platelet-free plasma for accurate quantitation. Pre-analytical factors influence the quantitation, interpretation, and implementation of circulating TARC as a biomarker for the development of AD therapeutics.

An ultra-sensitive clinical biomarker assay: quantitation of thymus and activation-regulated chemokine in human plasma.

Thymus and activation-regulated chemokine (TARC) is a Th2 type, pro-allergic secreted chemokine. TARC in plasma/serum has been proposed as a marker for disease activity of atopic dermatitis (AD) and as a pharmacodynamic readout in the clinical development of novel agents for the treatment of AD. An ultra-sensitive electrochemiluminescence assay for TARC in human plasma was developed and analytically validated. The assay demonstrated excellent performance characteristics, including precision, sensitivity, dilution linearity, accuracy and specificity. Stability and biological variability of TARC in plasma were also assessed for clinical sample analysis and data interpretation. The improved sensitivity allowed the measurement of approximately 90% TARC inhibition from baseline levels of healthy subjects and >90% TARC inhibition from baseline levels of AD patients after drug treatment. A validated TARC electrochemiluminescence assay enables pharmacodynamic assessment in the development of AD therapeutics.

アトピー性皮膚炎の医師による病勢評価の違いと血液検査での数値的な指標

アトピー性皮膚炎の医師による病勢評価の違いと血液検査での数値的な指標