A panel of biomarkers for disease severity in atopic dermatitis (original) (raw)
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New Developments in Biomarkers for Atopic Dermatitis
Journal of Clinical Medicine, 2015
The application of biomarkers in medicine is evolving. Biomarkers do not only give us a better understanding of pathogenesis, but also increase treatment efficacy and safety, further enabling more precise clinical care. This paper focuses on the current use of biomarkers in atopic dermatitis, new developments and future perspectives. Biomarkers can be used for many different purposes, including the objective determination of disease severity, confirmation of clinical diagnosis, and to predict response to treatment. In atopic dermatitis, many biomarkers have been investigated as a marker for disease severity. Currently serum thymus and activation-regulated chemokine (TARC) is the superior biomarker for assessing disease severity. However, we have recently shown that the use of a panel of serum biomarkers is more suitable for assessing disease severity than an individual biomarker. In this overview, we will discuss alternative sources for biomarkers, such as saliva and capillary blood, which can increase the user friendliness of biomarkers in atopic dermatitis (AD). Both methods offer simple, non-invasive and cost effective alternatives to venous blood. This provides great translational and clinical potential. Biomarkers will play an increasingly important role in AD research and personalized medicine. The use of biomarkers will enhance the efficacy of AD treatment by facilitating the individualization of therapy targeting the patients' specific biological signature and also by providing tools for predicting and monitoring of therapeutic response. OPEN ACCESS J. Clin. Med. 2015, 4 480
Atopic Dermatitis: Striving for Reliable Biomarkers
Journal of Clinical Medicine
Atopic dermatitis (AD) is a highly heterogeneous inflammatory disease regarding both its pathophysiology and clinical manifestations. However, it is treated according to the “one-size-fits-all” approach, which may restrict response to treatment. Thus, there is an unmet need for the stratification of patients with AD into distinct endotypes and clinical phenotypes based on biomarkers that will contribute to the development of precision medicine in AD. The development of reliable biomarkers that may distinguish which patients with AD are most likely to benefit from specific targeted therapies is a complex procedure and to date none of the identified candidate biomarkers for AD has been validated for use in routine clinical practice. Reliable biomarkers in AD are expected to improve diagnosis, evaluate disease severity, predict the course of disease, the development of comorbidities, or the therapeutic response, resulting in effective and personalized treatment of AD. Among the studied...
Journal of Allergy and Clinical Immunology
, and Therapy of Hereditary Angioedema Type III.'' Disclosure of potential conflict of interest: Z. L. M. Hofman received a European Academy of Allergy and Clinical Immunology travel grant for this work. T. Renn e's institution received a European Research Council grant for other works. H. Farkas received board membership from SOBI, Shire, Biocryst, and CSL Behring; consultancy fees from Shire; and payments for lectures from Pharming, CSL Behring, and Shire. The rest of the authors declare that they have no relevant conflicts of interest.
An Integrated Model of Atopic Dermatitis Biomarkers Highlights the Systemic Nature of the Disease
Journal of Investigative Dermatology, 2017
Current atopic dermatitis (AD) models link epidermal abnormalities in lesional skin to cytokine activation. However, there is evolving evidence of systemic immune activation and detectable abnormalities in nonlesional skin. Because some of the best single correlations with severity (Scoring of AD, or SCORAD) are detected not only in lesional but also nonlesional skin and blood, more complex biomarker models of AD are needed. We thus performed extensive biomarker measures in these compartments using univariate and multivariate approaches to correlate disease biomarkers with SCORAD and with a combined hyperplasia score [thickness and keratin 16 (K16) mRNA] at baseline and after cyclosporine A treatment in 25 moderate to severe AD patients. Increases in serum cytokines and chemokines (IL-13, IL-22, CCL17) were found in AD versus healthy individuals and were reduced with treatment. SCORAD correlated with immune (IL-13, IL-22) and epidermal (thickness, K16) measures in lesional and, even more strongly, in nonlesional AD. Serum cytokines also had higher correlations with nonlesional markers at baseline and with treatment. Multivariate U statistics improved baseline and treatment-response SCORAD correlations. Nonlesional models showed the strongest correlations, with further improvement upon integration of serum markers. Even better correlations were obtained between biomarkers and the hyperplasia score. Larger cohorts are needed to confirm these preliminary data.
Serum mucosa-associated epithelial chemokine in atopic dermatitis : A specific marker for severity
Indian Journal of Dermatology, 2009
Background Mucosa-associated epithelial chemokine (MEC; CCL28) is considered to be pivotal in mediating the migration of CC chemokine receptor 3-and 10-(CCR3-and CCR10)-expressing, skin-homing, memory, cutaneous lymphocyte-associated antigen-positive (CLA +) T cells. CCL28 is selectively and continuously expressed by epidermal keratinocytes, but highly upregulated in inflammatory skin diseases, such as atopic dermatitis (AD). Aim This controlled longitudinal study was designed to evaluate the expression of CCL28 in serum in childhood AD and bronchial asthma (BA), and its possible relationship to disease severity and activity. Methods Serum CCL28 levels were measured in 36 children with AD, 23 with BA, 14 with both conditions, and 21 healthy age-and sex-matched controls. Sixteen patients in the AD group were followed up and resampled for serum CCL28 after clinical remission. Serum CCL28 levels were correlated with some AD disease activity and severity variables. Results Serum CCL28 levels in AD, whether during flare [median, 1530 pg/mL; mean ± standard deviation (SD) ¼ 1590.4 ± 724.3 pg/mL] or quiescence (median, 1477 pg/mL; mean ± SD ¼ 1575.2 ± 522.1 pg/mL), were significantly higher than those in healthy children (median, 301 pg/mL; mean ± SD ¼ 189.6 ± 92.8 pg/mL); however, the levels during flare and quiescence were statistically comparable. The serum levels in BA (median, 340 pg/mL; mean ± SD ¼ 201.6 ± 109.5 pg/mL) were significantly lower than those in the AD group, and comparable with those in healthy controls. Serum CCL28 levels in severe AD were significantly higher than those in mild and moderate cases, and correlated positively with the calculated severity scores [Leicester Sign Score (LSS) and Scoring Atopic Dermatitis (SCORAD)]. CCL28 levels during the exacerbation of AD were positively correlated with the corresponding values during remission, the peripheral absolute eosinophil counts, and serum lactate dehydrogenase levels. Serum CCL28 levels were not correlated with the serum total immunoglobulin E values in AD. Conclusions Our data reinforce the concept that CCL28 might contribute to the pathogenesis of AD, probably through the selective migration and infiltration of effector/memory T-helper-2 cells in the skin. CCL28 may also represent an objective prognostic marker for disease severity. Further studies may pave the way for CCL28 antagonism among adjuvant therapeutic strategies.
Journal of Allergy and Clinical Immunology, 2001
Objective: The purpose of this study was to investigate the participation of TARC in AD. Methods: We measured serum TARC levels in 40 patients with AD, 20 healthy control subjects, and 20 patients with psoriasis. We also examined disease activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor, IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as correlations between TARC levels and these factors. The positivity of CCR4 of CD4 + CD45RO + cells in PBMCs was examined by using FACS analysis. Immunohistochemical staining of TARC and GM-CSF was performed in the lesional skin of patients with AD. Results: The serum TARC levels of patients with AD were significantly higher than those of healthy control subjects and patients with psoriasis. The serum TARC levels significantly correlated with eosinophil number (r = 0.61), SCORAD score (r = 0.60), and serum soluble E-selectin levels (r = 0.58) and weakly correlated with serum soluble IL-2 receptor levels (r = 0.34) in patients with AD. The TARC levels of patients with AD decreased after the treatment in accordance with the improvement of clinical symptoms. The CCR4 positivity of CD4 + CD45RO + cells in PBMCs of patients with AD was also higher than that of healthy control subjects. Immunohistochemical staining revealed that TARC was positive in keratinocytes in the epidermis and in vascular endothelial cells, T cells, and dendritic cells in the dermis. Conclusion: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD. (J Allergy Clin Immunol 2001;107:535-41.)
British Journal of Dermatology, 1992
Atopic dermatitis (AD) is characterized by alterations in cellular and humoral immunity including elevated serum levels of IgE, IL-2 receptor (IL-2R) and eosinophil cationic protein (ECP). In order to evaluate the relevance of these serum parameters as indicators of disease activity, the concentrations of IgE, IL-2R and ECP were measured in serum samples of patients with an acute exacerbation of AD (n=19) on admission to hospital and every 6 days up to discharge, and compared with those from normal non-atopic controls (n= 15). The severity of the disease in the AD patients was examined using an established clinical scoring system. On admission, AD patients showed significantly elevated serum levels of IgE, IL-2R and ECP compared with normal controls (P≤0.0001). Clinical improvement was associated with a decrease of both the clinical score (P≤0.001) and serum ECP levels (P≤0.005). No significant changes in serum IgE and serum IL-2R were observed. In addition, there was a significant correlation between serum ECP and the clinical score (R=0.67, P≤0.001). These data indicate that serum ECP may be a helpful tool for monitoring disease activity in AD.
Acta Dermato Venereologica
To date, the relationship between the 2 different types of severity-indicating parameters (i.e. between subjective and objective severity-indicating parameters) in patients with atopic dermatitis has not been sufficiently elucidated. This study elucidates the relationship between the subjective and objective severity-indicating parameters in atopic dermatitis. Eosinophil relative count in the peripheral blood is considered to correlate with degree of itch in patients with atopic dermatitis, while neutrophil-to-lymphocyte ratio in the peripheral blood is considered to correlate with the degree of inflammation and the area of the affected region. Eosinophil relative count and neutrophil-to-lymphocyte ratio may be stand-alone parameters from each other in the assessment of the severity of atopic dermatitis. The aim of this study is to elucidate the relationship between 2 different types of severity-indicating parameters (i.e. between subjective and objective severityindicating parameters in patients with atopic dermatitis. The disease severity of 55 patients with atopic dermatitis was assessed using 7 subjective parameters indicating severity, including visual analogue scale for itch, Patient-Oriented Eczema Measure, 5-D itch scale, Dermatology Life Quality Index, Eczema Area and Severity Index, body surface area, and Investigator Global Assessment, and 8 objective parameters indicating severity, including eosinophil relative count, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and thymus and activation-regulated chemokine. Five subjective parameters reflecting itch correlated significantly with eosinophil relative count, but not with neutrophil-to-lymphocyte ratio. In contrast, 2 subjective parameters, mainly reflecting the degree of inflammation and area of affected regions, correlated significantly with neutrophil-to-lymphocyte ratio. The eosinophil relative count may correlate with the degree of itch, while the neutrophil-to-lymphocyte ratio may correlate with the degree of inflammation and the area of the affected region. The eosinophil relative count and neutrophil-to-lymphocyte ratio may thus be stand-alone parameters from each other in the assessment of the severity of atopic dermatitis.