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Artikel ; Online: Proteomic alterations in patients with atopic dermatitis.

Obi, Ashley / Rothenberg-Lausell, Camille / Levit, Sophia / Del Duca, Ester / Guttman-Yassky, Emma

2024 , Seite(n) 1–11

Abstract: Introduction: Atopic Dermatitis (AD) is the most common inflammatory skin disease with a complex and multifactorial pathogenesis. The use of proteomics in understanding AD has yielded the discovery of novel biomarkers and may further expand therapeutic ... ...

Abstract	Introduction: Atopic Dermatitis (AD) is the most common inflammatory skin disease with a complex and multifactorial pathogenesis. The use of proteomics in understanding AD has yielded the discovery of novel biomarkers and may further expand therapeutic options. Areas covered: This review summarizes the most recent proteomic studies and the methodologies used in AD. It describes novel biomarkers that may monitor disease course and therapeutic response. The review also highlights skin and blood biomarkers characterizing different AD phenotypes and differentiates AD from other inflammatory skin disorders. A literature search was conducted by querying Scopus, Google Scholar, Pubmed/Medline, and Clinicaltrials.gov up to June 2023. Expert opinion: The integration of proteomics into research efforts in atopic dermatitis has broadened our understanding of the molecular profile of AD through the discovery of new biomarkers. In addition, proteomics may contribute to the development of targeted treatments ultimately improving personalized medicine. An increasing number of studies are utilizing proteomics to explore this heterogeneous disease.
Sprache	Englisch
Erscheinungsdatum	2024-05-22
Erscheinungsland	England
Dokumenttyp	Journal Article ; Review
ZDB-ID	2299100-1
ISSN	1744-8387 ; 1478-9450
ISSN (online)	1744-8387
ISSN	1478-9450
DOI	10.1080/14789450.2024.2350938
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Biologic and small-molecule therapy for treating moderate to severe atopic dermatitis: Mechanistic considerations.

Rothenberg-Lausell, Camille / Bar, Jonathan / Dahabreh, Dante / Renert-Yuval, Yael / Del Duca, Ester / Guttman-Yassky, Emma

The Journal of allergy and clinical immunology

2024

Abstract: Atopic dermatitis (AD) is a complex and heterogeneous skin disease for which achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role ... ...

Abstract	Atopic dermatitis (AD) is a complex and heterogeneous skin disease for which achieving complete clinical clearance for most patients has proven challenging through single cytokine inhibition. Current studies integrate biomarkers and evaluate their role in AD, aiming to advance our understanding of the diverse molecular profiles implicated. Although traditionally characterized as a T
Sprache	Englisch
Erscheinungsdatum	2024-04-24
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2024.04.009
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Diversity of atopic dermatitis and selection of immune targets.

Rothenberg-Lausell, Camille / Bar, Jonathan / Del Duca, Ester / Guttman-Yassky, Emma

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

2023 Band 132, Heft 2, Seite(n) 177–186

Abstract: Atopic dermatitis (AD) is a heterogeneous immune-mediated skin disorder affecting people of all ages and ethnicities. Despite the development of targeted therapeutics such as biologics and Janus kinase inhibitors, attaining complete clinical efficacy ... ...

Abstract	Atopic dermatitis (AD) is a heterogeneous immune-mediated skin disorder affecting people of all ages and ethnicities. Despite the development of targeted therapeutics such as biologics and Janus kinase inhibitors, attaining complete clinical efficacy remains difficult. This therapeutic challenge may be attributed to the complex pathogenesis of AD. Although the T
Mesh-Begriff(e)	Humans ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/genetics ; Immunoglobulin E ; Th2 Cells ; Skin/pathology ; Cytokines/metabolism
Chemische Substanzen	Immunoglobulin E (37341-29-0) ; Cytokines
Sprache	Englisch
Erscheinungsdatum	2023-11-24
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Review
ZDB-ID	1228189-x
ISSN	1534-4436 ; 0003-4738 ; 1081-1206
ISSN (online)	1534-4436
ISSN	0003-4738 ; 1081-1206
DOI	10.1016/j.anai.2023.11.020
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Skin tape-strips in old order Mennonite toddlers reveal upregulated barrier markers and low T-helper inflammatory tone.

Rothenberg-Lausell, Camille / David, Eden / Del Duca, Ester / Da Rosa, Joel Correa / Dahabreh, Dante / Gómez-Arias, Pedro Jesús / Catlin, Elizabeth / Nandymazumdar, Monali / Järvinen, Kirsi M / Guttman-Yassky, Emma

Allergy

2024

Sprache	Englisch
Erscheinungsdatum	2024-05-30
Erscheinungsland	Denmark
Dokumenttyp	Letter
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.16154
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Age of onset defines two distinct profiles of atopic dermatitis in adults

Facheris, Paola / Da Rosa, Joel Correa / Pagan, Angel D. / Angelov, Michael / Del Duca, Ester / Rabinowitz, Grace / Gómez‐Arias, Pedro Jesús / Rothenberg‐Lausell, Camille / Estrada, Yeriel D. / Bose, Swaroop / Chowdhury, Mashkura / Shemer, Avner / Pavel, Ana B. / Guttman‐Yassky, Emma

Allergy. 2023 Aug., v. 78, no. 8, p. 2202-2214

2023 , Seite(n) 2202–2214

Abstract: BACKGROUND: The incidence of adult‐onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric‐onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted‐ ... ...

Abstract	BACKGROUND: The incidence of adult‐onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric‐onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted‐therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD. METHODS: We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT‐PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile. RESULTS: Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL‐36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p‐value < .05). In contrast, higher Th1‐(IFN‐γ, IL‐2, IL‐15, CCL5) upregulation and Th1‐skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro‐inflammatory and cardiovascular‐risk markers. Th1‐related products showed significant correlations between their skin and blood expressions only in AOAD subjects. CONCLUSION: Age‐of‐onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.
Schlagwörter	RNA ; adulthood ; adults ; atopic dermatitis ; blood serum ; cell adhesion ; hyperplasia ; immunohistochemistry ; inflammation ; interleukin-15 ; interleukin-2 ; proteomics ; therapeutics
Sprache	Englisch
Erscheinungsverlauf	2023-08
Umfang	p. 2202-2214
Erscheinungsort	John Wiley & Sons, Ltd
Dokumenttyp	Artikel ; Online
Anmerkung	JOURNAL ARTICLE
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15741
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel: Do Atopic Dermatitis Patient-Reported Outcomes Correlate With Validated Investigator Global Assessment? Insights From TARGET-AD Registry.

Guttman-Yassky, Emma / Bar, Jonathan / Rothenberg-Lausell, Camille / Eichenfield, Lawrence / Grada, Ayman / Abuabara, Katrina / Chapman, M / Calimlim, Brian / Wegzyn, Colleen / Gamelli, Amy / Krueger, Whitney / Munoz, Breda / Knapp, Keith / Faller, Rachel / Crawford, Julie / Silverberg, Jonathan

Journal of drugs in dermatology : JDD

2023 Band 22, Heft 4, Seite(n) 344–354

Abstract: Background: Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient- ...

Abstract	Background: Research examining associations between the clinician-reported validated Investigator Global Assessment for AD (vIGA-AD) and patient-reported disease burden is sparse. This study aims to evaluate the relationship between vIGA-AD with patient-reported disease severity and quality of life (QoL). Methods: A cross-sectional analysis was conducted using a September 2021 data cut from the TARGET-DERM AD study, a real-world, longitudinal cohort of children, adolescents, and adults with AD enrolled at 44 academic and community dermatology and allergy sites in the US. Clinical AD severity was measured using vIGA-AD while disease severity and QoL were assessed by the Patient Oriented Eczema Measure (POEM) and (Children’s) Dermatology Life Quality Index (C/DLQI), respectively. Patient characteristics, clinical- and patient reported-outcomes were assessed by stratified POEM and C/DLQI categories using descriptive statistics. Associations with vIGA-AD were evaluated using unadjusted and adjusted ordinal logistic regression and linear regression models. Results: The analysis cohort (n=1,888) primarily consisted of adults (57%), females (56%), and patients with private insurance (63%). Unadjusted analyses suggest that clinical AD severity was associated with age, with more adolescents and adults having moderate/severe vIGA-AD than pediatric patients. Clinical AD severity was also associated with disease severity, with greater POEM scores observed at greater vIGA-AD severity levels (r = 0.496 and 0.45 for adults and pediatrics, respectively). Clinical AD severity and QoL were positively correlated, with greater CDLQI/DLQI scores at greater vIGA-AD severity levels (r = 0.458 and 0.334 for DLQI and CDLQI, respectively). After adjusting for demographics and other risk factors, vIGA-AD continued to show significant associations with POEM and DLQI/CDLQI. Compared to patients with clear/almost clear disease, adults and pediatrics with moderate-to-severe AD were 8.19 and 5.78 times as likely to be in a more severe POEM category, respectively. Similarly, compared to patients with clear/almost clear disease, adults and pediatrics with moderate/severe AD were 6.69 and 3.74 times as likely to be in a more severe DLQI/CDLQI category. Adjusted linear regression analyses of DLQI in adults showed significant differences by vIGA-AD level, with mild AD and moderate/severe AD associated with a 2.26-point and 5.42-point greater DLQI relative to clear/almost clear AD. Conclusions: In this real-world study of patients with AD, greater clinician-reported disease severity is positively correlated with higher patient-reported disease severity and lower QoL. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7473 Access Supplementary Material here Citation: Guttman-Yassky E, Bar J, Rothenberg Lausell C, et al. Do atopic dermatitis patient-reported outcomes correlate with validated investigator global assessment? Insights from TARGET-AD registry. J Drugs Dermatol. 2023;22(4):344-355. doi:10.36849/JDD.7473.
Mesh-Begriff(e)	Adult ; Female ; Adolescent ; Humans ; Child ; Dermatitis, Atopic/diagnosis ; Quality of Life ; Cross-Sectional Studies ; Surveys and Questionnaires ; Severity of Illness Index ; Patient Reported Outcome Measures ; Registries
Sprache	Englisch
Erscheinungsdatum	2023-04-07
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2145090-0
ISSN	1545-9616
ISSN	1545-9616
DOI	10.36849/JDD.7473
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Oral difelikefalin reduces moderate to severe pruritus and expression of pruritic and inflammatory biomarkers in subjects with atopic dermatitis.

Guttman-Yassky, Emma / Facheris, Paola / Da Rosa, Joel Correa / Rothenberg-Lausell, Camille / Del Duca, Ester / David, Eden / Estrada, Yeriel / Liu, Ying / Bose, Swaroop / Chowdhury, Mashkura / Munera, Catherine / Goncalves, Joana / Nograles, Kristine / Kim, Brian S / Lebwohl, Mark

The Journal of allergy and clinical immunology

2023 Band 152, Heft 4, Seite(n) 916–926

Abstract: Background: Pruritus is the most common and burdensome symptom of atopic dermatitis (AD). Pruritus-targeted treatments in AD are lacking, particularly for patients with milder skin disease.: Objective: We sought to evaluate the impact of the ... ...

Abstract	Background: Pruritus is the most common and burdensome symptom of atopic dermatitis (AD). Pruritus-targeted treatments in AD are lacking, particularly for patients with milder skin disease. Objective: We sought to evaluate the impact of the selective κ-opioid receptor agonist difelikefalin (DFK) on pruritus intensity and pruritus- and immune-related biomarkers in subjects with moderate to severe AD-related pruritus. Methods: A phase 2 clinical trial investigated the efficacy and safety of oral DFK 0.25, 0.5, and 1.0 mg in subjects with moderate to severe AD-related pruritus. A biomarker substudy evaluated the effects of DFK on the expression of pruritus, T Results: In the clinical trial (N = 401), all DFK doses reduced itch versus placebo; however, the results were not statistically significant at week 12. In a subgroup of subjects in the trial with mild to moderate skin inflammation and moderate to severe itch (itch-dominant AD phenotype), DFK reduced itch at week 12 versus placebo. In the biomarker substudy, DFK downregulated the expression of key pruritus-related genes (eg, IL-31 and TRPV1) and the AD phenotype (eg, CCL17). Gene set variation analysis confirmed that DFK, but not placebo, downregulated pruritus-related genes and T Conclusions: DFK treatment reduced itch in subjects with moderate to severe AD-related pruritus, particularly those with an "itch-dominant" AD phenotype, and had an impact on the expression of pruritus, T
Mesh-Begriff(e)	Humans ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/metabolism ; Pruritus/drug therapy ; Pruritus/metabolism ; Skin/metabolism ; Biomarkers/metabolism ; Severity of Illness Index
Chemische Substanzen	difelikefalin (NA1U919MRO) ; Biomarkers
Sprache	Englisch
Erscheinungsdatum	2023-07-13
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2023.06.023
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Age of onset defines two distinct profiles of atopic dermatitis in adults.

Facheris, Paola / Da Rosa, Joel Correa / Pagan, Angel D / Angelov, Michael / Del Duca, Ester / Rabinowitz, Grace / Gómez-Arias, Pedro Jesús / Rothenberg-Lausell, Camille / Estrada, Yeriel D / Bose, Swaroop / Chowdhury, Mashkura / Shemer, Avner / Pavel, Ana B / Guttman-Yassky, Emma

Allergy

2023 Band 78, Heft 8, Seite(n) 2202–2214

Abstract: Background: The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted- ... ...

Abstract	Background: The incidence of adult-onset atopic dermatitis (AOAD) is increasing. However, the unique characteristics of AOAD compared to pediatric-onset AD persisting into adulthood (POAD) are underexplored, hampering the development of targeted-therapeutics for this growing population. We thus assessed the profile of AOAD in skin and blood compared to that of POAD. Methods: We collected skin biopsies and blood from adults with AOAD, POAD, and healthy controls (n = 15 in each group). Skin samples were analyzed by RNA sequencing, qRT-PCR, and immunohistochemistry, and Olink Proseek multiplex assay was used to identify the serum proteomic profile. Results: Compared to healthy controls, both AOAD and POAD showed cutaneous immune and barrier dysregulations with a shared Th2/Th22 hyperactivation. Overall, POAD showed greater inflammation in lesional skin, with more prominent expression of Th2/Th17/Th22 markers (CCL17/22, S100A8/9, IL-36A, PI3/Elafin, DEFB4) in POAD compared to AOAD (p-value < .05). In contrast, higher Th1-(IFN-γ, IL-2, IL-15, CCL5) upregulation and Th1-skewing were seen in AOAD. The epidermal barrier was also more compromised in POAD, with greater epidermal hyperplasia and lower expression of markers related to terminal differentiation, lipids, and cell adhesion. In parallel with increased rates of cardiovascular comorbidities, AOAD demonstrated many more significantly dysregulated proteins in serum (n = 148) compared to POAD (n = 86), including pro-inflammatory and cardiovascular-risk markers. Th1-related products showed significant correlations between their skin and blood expressions only in AOAD subjects. Conclusion: Age-of-onset delineates two distinct endophenotypes in adult AD potentially suggesting the need for broader (beyond Th2) therapeutic targeting in AOAD.
Mesh-Begriff(e)	Child ; Adult ; Humans ; Dermatitis, Atopic/diagnosis ; Dermatitis, Atopic/epidemiology ; Dermatitis, Atopic/genetics ; Age of Onset ; Proteomics ; Skin/pathology ; Inflammation/pathology
Sprache	Englisch
Erscheinungsdatum	2023-04-18
Erscheinungsland	Denmark
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15741
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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